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Sall I, Foxall R, Felth L, Maret S, Rosa Z, Gaur A, Calawa J, Pavlik N, Whistler JL, Whistler CA. Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine. Gut Microbes 2025; 17:2446423. [PMID: 39800714 PMCID: PMC11730370 DOI: 10.1080/19490976.2024.2446423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 11/24/2024] [Accepted: 12/18/2024] [Indexed: 01/16/2025] Open
Abstract
The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.
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Affiliation(s)
- Izabella Sall
- Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA
- Graduate program in Molecular and Evolutionary Systems Biology, University of New Hampshire, Durham, NH, USA
| | - Randi Foxall
- Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA
| | - Lindsey Felth
- Center for Neuroscience, University of California–Davis, Davis, CA, USA
| | - Soren Maret
- Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA
| | - Zachary Rosa
- Center for Neuroscience, University of California–Davis, Davis, CA, USA
| | - Anirudh Gaur
- Center for Neuroscience, University of California–Davis, Davis, CA, USA
| | - Jennifer Calawa
- Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA
- Microbiology Graduate Program, University of New Hampshire, Durham, NH, USA
| | - Nadia Pavlik
- Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA
| | - Jennifer L. Whistler
- Center for Neuroscience, University of California–Davis, Davis, CA, USA
- Department of Physiology and Membrane Biology, UC Davis School of Medicine, Davis, CA, USA
| | - Cheryl A. Whistler
- Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA
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Liang M, Deng Z, Wu W, Dong Q, Fan J. Study on the correlation between intestinal flora and cytokines in children with Henoch-Schönlein purpura. Cytokine 2025; 191:156959. [PMID: 40373421 DOI: 10.1016/j.cyto.2025.156959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Revised: 04/20/2025] [Accepted: 05/05/2025] [Indexed: 05/17/2025]
Abstract
BACKGROUND The pathogenesis of Henoch-Schönlein purpura (HSP) is complex. It is currently believed that the development of HSP involves abnormalities in humoral immunity and cellular immunity. The intestinal microbiota has a powerful regulatory effect on the human immune system and has been shown to serve a significant role in the pathogenesis of various immune-mediated disorders. This study examines changes in intestinal flora and cytokines(IFN-γ, IL-4, IL-10, and IL-17) in children with HSP and explores their correlation, offering fresh insights for the prevention and treatment of HSP. METHODS Blood and stool specimens were collected from 25 healthy children (control group) and 27 children with HSP (observation group). Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of cytokines IFN-γ, IL-4, IL-17, and IL-10 in the serum of all the study participants, and the 16S rRNA gene sequencing combined with high-throughput sequencing technology was used to analyze the intestinal flora of the study subjects. Finally, the correlation between serum cytokines and gut microbiota was analyzed in the children with HSP. RESULT 1)The serum levels of IL-4 and IL-17 in the observation group were higher than those in the control group, while the levels of IFN-γ and IL-10 were lower than those in the control group. 2) At the level of phylum, the abundance of Fusobacteria and Verrucomicrobia was higher than that in the control group, while the abundance of Firmicutes was lower than that of the control group, and the differences were statistically significant (P < 0.05); At the level of genus, the abundance of Prevotella and Akkermansia were higher than the control group, while the abundance of Bifidobacterium, Blautia, and Clostridium XlVa was lower than that in the control group, and the differences were all statistically significant (P < 0.05); At the species level, the abundance of Akkermansia muciniphila, Prevotella copri, and Subdoligranulum variabile was higher than that of the control group, while the abundance of Bifidobacterium pseudolongum, Brautella Weiss, and Bacteroides fragilis was lower than that in the control group, and the differences were statistically significant (P < 0.05). 3) The abundance of Blautia and Blautia wexlerae in the observation group was positively associated with the IL-10 level (r = 0.522, r = 0.578, P < 0.01). CONCLUSION Disturbances in intestinal flora and changes in serum cytokines IFN-γ, IL-4, IL-10, and IL-17 were present in children with HSP. The abundance of Blautia and Blautia wexlerae in the gut microbiota of children with HSP was positively correlated with serum IL-10 levels.
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Affiliation(s)
- Mingxin Liang
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China; Department of Pediatrics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China
| | - Zhaoxu Deng
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China
| | - Weiyi Wu
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China; Department of Pediatrics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China
| | - Qinqin Dong
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China.; Department of Pediatrics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China
| | - Juan Fan
- Department of Pediatrics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China..
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Gong W, Jin G, Bao Y, Liu Q, Ni M, Wang J, Mao S, Zhang Y, Zheng Z. Characteristics and potential diagnostic value of gut microbiota in ovarian tumor patients. Sci Rep 2025; 15:16504. [PMID: 40360697 PMCID: PMC12075642 DOI: 10.1038/s41598-025-99912-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
The gut microbiota is closely related to the occurrence and development of cancer. However, the characteristics of gut microbiota associated with ovarian tumors remain elusive. In this study, fecal samples were collected from healthy control (HC) group and patients with ovarian tumor (OT) or with other benign tumor (OBT) for 16s rRNA sequencing to determine differential flora in gut microbiota. The composition of gut microbiota in the OT group, including bacterial abundance and diversity, was significantly different form HC and OBT groups. In the OT group, Escherichia_Shigella was markedly higher than in the HC group, while Coprococcus, Fusicatenibacter, Butyricicoccus and Oscillibacter were significantly lower than in HCs. The abundance of Fusicatenibacter, Butyricicoccus, Coprococcus Parasutterella, and Anaerotruncus in the OBT group was distinctly higher than that in the OT group, while the Lachnospiracae_ND3007_group was significantly lower. In addition, in OT patients, ovarian cancer (OC) and benign ovarian tumor (BOT) patients also showed a unique composition of gut microbiota. The random forest model was designed using different bacteria. Compared with HCs, area under curve (AUC) values for BOT and OC groups were 0.77 and 0.86, respectively. These findings suggest that some gut microbiota such as Escherichia_Shigella show a certain ability to distinguish between healthy individuals and patients with OT.
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Affiliation(s)
- Wangang Gong
- Zhejiang Cancer Hospital, Banshan Road, Hangzhou, 310022, Zhejiang, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Gulei Jin
- Hangzhou Guhe Information and Technology Company, Hangzhou, Zhejiang, China
| | - Yejiang Bao
- Zhejiang Cancer Hospital, Banshan Road, Hangzhou, 310022, Zhejiang, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Qi Liu
- Zhejiang Cancer Hospital, Banshan Road, Hangzhou, 310022, Zhejiang, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Maowei Ni
- Zhejiang Cancer Hospital, Banshan Road, Hangzhou, 310022, Zhejiang, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Junjian Wang
- Zhejiang Cancer Hospital, Banshan Road, Hangzhou, 310022, Zhejiang, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Shuyu Mao
- Zhejiang Cancer Hospital, Banshan Road, Hangzhou, 310022, Zhejiang, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Yingli Zhang
- Zhejiang Cancer Hospital, Banshan Road, Hangzhou, 310022, Zhejiang, China.
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
| | - Zhiguo Zheng
- Zhejiang Cancer Hospital, Banshan Road, Hangzhou, 310022, Zhejiang, China.
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
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Dai Y, Vgontzas AN, Chen L, Zheng D, Chen B, Wu J, Shao R, Li Y. A multi-omics study of the association between insomnia with objective short sleep duration phenotype and high blood pressure. Sleep 2025; 48:zsaf030. [PMID: 39888642 DOI: 10.1093/sleep/zsaf030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 01/26/2025] [Indexed: 02/01/2025] Open
Abstract
STUDY OBJECTIVES Insomnia with objective short sleep duration is associated with increased hypertension risk. We aimed to explore the mechanism underlying the association between objective short sleep duration and hypertension in patients with chronic insomnia disorder (CID) by multi-omics. METHODS CID was defined according to International Classification of Sleep Disorders-3, and objective short sleep duration was based on the median value of total sleep time of the overall subjects during an overnight polysomnography. We used the mean values of measured nighttime and morning systolic (SBP) and diastolic blood pressure (DBP) for analysis. Serum metabolomics and fecal 16S rDNA amplicon sequencing were used to explore characteristic metabolites and analyze gut microbiota distribution, respectively. RESULTS One hundred and three patients with CID and 70 normal sleepers were included. We found 52 objective short sleep duration insomnia phenotype (ISSD)-related serum metabolites. Among the 52 ISSD-related serum metabolites, indoxyl sulfate was positively correlated with BP after adjusting for confounding factors (SBP: β = 0.250, p = .028; DBP: β = 0.256, p = .030) in ISSD. In addition, the level of serum indoxyl sulfate was significantly correlated with the genera Prevotella 9 (r = .378, p = .027), CAG-56 (r = -.359, p = .037), Ruminiclostridium 9 (r = -.340, p = .049), and Ruminococcus 2 (r = -.356, p = .039) in ISSD. CONCLUSIONS Our study suggests that the ISSD phenotype is associated with significant changes in serum metabolic profile, including high levels of indoxyl sulfate. The latter molecule correlates both with BP and gut microbiota in patients with the ISSD phenotype, suggesting that indoxyl sulfate may be the molecular path resulting in increased hypertension risk in this phenotype.
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Affiliation(s)
- Yanyuan Dai
- Department of Sleep Medicine, Shantou University Mental Health Center, Shantou, Guangdong, China
- Sleep Medicine Center, Shantou University Medical College, Shantou, Guangdong, China
- Shantou University Medical College-Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou, Guangdong, China
| | - Alexandros N Vgontzas
- Sleep Research and Treatment Center, Department of Psychiatry and Behavioral Health, Pennsylvania State University, College of Medicine, Hershey, PA, USA
| | - Le Chen
- Department of Sleep Medicine, Shantou University Mental Health Center, Shantou, Guangdong, China
- Sleep Medicine Center, Shantou University Medical College, Shantou, Guangdong, China
- Shantou University Medical College-Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou, Guangdong, China
| | - Dandan Zheng
- Department of Sleep Medicine, Shantou University Mental Health Center, Shantou, Guangdong, China
- Sleep Medicine Center, Shantou University Medical College, Shantou, Guangdong, China
- Shantou University Medical College-Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou, Guangdong, China
| | - Baixin Chen
- Department of Sleep Medicine, Shantou University Mental Health Center, Shantou, Guangdong, China
- Sleep Medicine Center, Shantou University Medical College, Shantou, Guangdong, China
- Shantou University Medical College-Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou, Guangdong, China
| | - Jun Wu
- Department of Sleep Medicine, Shantou University Mental Health Center, Shantou, Guangdong, China
- Sleep Medicine Center, Shantou University Medical College, Shantou, Guangdong, China
- Shantou University Medical College-Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou, Guangdong, China
| | - Ruifan Shao
- Department of Sleep Medicine, Shantou University Mental Health Center, Shantou, Guangdong, China
- Sleep Medicine Center, Shantou University Medical College, Shantou, Guangdong, China
- Shantou University Medical College-Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou, Guangdong, China
| | - Yun Li
- Department of Sleep Medicine, Shantou University Mental Health Center, Shantou, Guangdong, China
- Sleep Medicine Center, Shantou University Medical College, Shantou, Guangdong, China
- Shantou University Medical College-Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou, Guangdong, China
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Xu L, He R, Ye X, Wang Y, Hui S, Li H, Chen H, Huang P. Leveraging transcriptome-wide association studies identifies the relationship between upper respiratory flora and cell type-specific gene expression in severe respiratory disease. PLoS One 2025; 20:e0322864. [PMID: 40343915 PMCID: PMC12063895 DOI: 10.1371/journal.pone.0322864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 03/30/2025] [Indexed: 05/11/2025] Open
Abstract
ObjectivesThe upper respiratory tract flora may influence host immunity and modulate susceptibility to viral respiratory infections. This study aimed to investigate the associations between upper respiratory tract flora and immune cells in severe ILI, identify specific microbial taxa and immune response pathways contributing to disease severity, and elucidate how flora influences ILI progression by modulating immune cell functions.MethodsHeritability of GWAS summary data was estimated using LDSC (v1.0.1). Gene-level genetic associations were analyzed with MAGMA. scRNA-seq data were integrated with genetic association data using scDRS. FUSION was used to construct cell type-specific expression quantitative trait locus models based on genotypes and scRNA-seq data from the onek1k project, which were combined with flora abundance-related GWAS data for a transcriptome-wide association study.ResultsFrom the LDSC analysis, data from 1195 severe ILI-associated GWASs with upper respiratory flora(h2 > 0.1) were included in subsequent analysis. TWAS identified 19 significant association pairs (Padj < 0.05), and 1226 differentially expressed genes between mild and severe ILI patients (Padj < 0.05 and | log2FC|>0.25). Functional enrichment analyses using GO, KEGG, and Reactome databases revealed that immune cells,such as CD4 + T effector memory cells, cDCs, NK cells, were enriched in multiple biological processes or pathways.ConclusionsThis study identified associations between severe ILI-related upper respiratory tract flora and cell type-specific gene expression, potentially explaining how differential flora influences ILI progression. CD16 + monocytes exhibited the most differentially expressed genes, followed by proliferating cells and cDCs, highlighting the significant role of immune cell-enriched pathways in ILI progression.
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Affiliation(s)
- Lei Xu
- Depatment of Epidemiology, Center for Global Health, School of Public Health, National Vaccine Innovation Platiorm, Nanjing Medical University, Nanjing, China
| | - Ran He
- Depatment of Epidemiology, Center for Global Health, School of Public Health, National Vaccine Innovation Platiorm, Nanjing Medical University, Nanjing, China
| | - Xiangyu Ye
- Depatment of Epidemiology, Center for Global Health, School of Public Health, National Vaccine Innovation Platiorm, Nanjing Medical University, Nanjing, China
| | - Yifan Wang
- Department of Infectious Disease, Jurong Hospital Affiliated to Jiangsu University, Jurong, Jiangsu, China
| | - Shirong Hui
- Depatment of Epidemiology, Center for Global Health, School of Public Health, National Vaccine Innovation Platiorm, Nanjing Medical University, Nanjing, China
| | - Haochang Li
- Depatment of Epidemiology, Center for Global Health, School of Public Health, National Vaccine Innovation Platiorm, Nanjing Medical University, Nanjing, China
| | - Hongbo Chen
- Department of Infectious Disease, Jurong Hospital Affiliated to Jiangsu University, Jurong, Jiangsu, China
| | - Peng Huang
- Depatment of Epidemiology, Center for Global Health, School of Public Health, National Vaccine Innovation Platiorm, Nanjing Medical University, Nanjing, China
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Liu Q, Song M, Wang Y, Zhang P, Zhang H. CCL20-CCR6 signaling in tumor microenvironment: Functional roles, mechanisms, and immunotherapy targeting. Biochim Biophys Acta Rev Cancer 2025; 1880:189341. [PMID: 40348067 DOI: 10.1016/j.bbcan.2025.189341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 05/01/2025] [Accepted: 05/05/2025] [Indexed: 05/14/2025]
Abstract
Chemokine CC motif ligand 20 (CCL20) is a molecule with immunomodulatory properties that is involved in the regulation of diseases such as chronic inflammation, autoimmune diseases, and cancer. It operates by binding to its specific receptor, CC chemokine receptor type 6 (CCR6), and activating a complex intracellular signaling network. Building on its established role in inflammatory diseases, recent research has expanded our understanding of CCL20 to encompass its critical contributions to the tumor microenvironment (TME), highlighting its significance in cancer progression. Numerous studies have emphasized its prominent role in regulating immune responses. Consequently, Monoclonal antibodies against CCL20 and inhibitors of CCR6 have been successfully developed to block downstream signaling, making the CCL20-CCR6 axis a promising and critical target in the TME. This offers potential immunotherapeutic strategies for cancers. In this review, we summarize the biological consequences of CCL20-CCR6 mediated signaling, its role and mechanisms in the TME, and its potential applications. We suggest that the CCL20-CCR6 axis may be a novel biomarker for tumor diagnosis and prognosis, as well as a therapeutic target in various cancers.
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Affiliation(s)
- Qi Liu
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Mingyuan Song
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Yan Wang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
| | - Ping Zhang
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Hao Zhang
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, China.
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Zegeye FD, Straumfors A, Lei P, Graff P, Samulin Erdem J, Afanou AK. Microbial exposure and diversity in Norwegian shrimp processing plants. JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE 2025:1-14. [PMID: 40324108 DOI: 10.1080/15459624.2025.2491488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Abstract
Seafood processing workers have a high prevalence of respiratory symptoms and occupational asthma, primarily attributed to allergenic protein exposure. However, exposure to airborne microorganisms from raw materials can also contribute to allergic sensitization and other respiratory ailments. This study aimed to assess microbial exposure in shrimp processing plants and identify susceptible work tasks. Full-shift personal air samples were collected from two Norwegian shrimp processing plants across five distinct work processes: thawing, truck driving, cooking-peeling (technician), packing, and flour production. The samples were analyzed for the presence of endotoxin, Toll-Like Receptor (TLR) activation, bacterial and fungal DNA copies, and microbial composition. Endotoxin levels were generally low, with only one sample (98 EU/m3) exceeding the recommended occupational exposure limit (OEL). A significant TLR2 activation was observed among thawers, indicating the presence of microbial ligands capable of triggering an immune response. The median bacterial (75 × 103 DNA copies/m3) and fungal (3,301 × 103 DNA copies/m3) exposure were highest among the flour production workers, while the lowest bacterial and fungal exposure was among packers (1.5 × 103 DNA copies/m3) and technicians (337 DNA copies/m3), respectively. Several bacterial and fungal species were identified, including ten allergenic and sixteen pathogenic species. Sporobolomyces roseus and Saccharomyces cerevisiae were the two most frequently identified allergenic fungal species. Among the pathogenic bacterial species, Prevotella nigrescens and Roseomonas gilardii were the two most detected species. While the pathogenic species were identified mainly in the packing, truck driving, and flour production work processes, most of the allergenic species were found in all work processes. Altogether, work processes before the cooking of shrimp (thawing and truck driving) had higher endotoxin, bacterial load, and species richness than after cooking, suggesting that these work tasks are susceptible to bacterial exposure and that the cooking process significantly reduces bacterial exposure. By shedding light on microbial exposure and identifying high-exposure work tasks, this study enables the development of targeted interventions and implementation of measures for the prevention of occupational diseases.
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Affiliation(s)
- Fikirte Debebe Zegeye
- National Institute of Occupational Health (STAMI), Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Anne Straumfors
- National Institute of Occupational Health (STAMI), Oslo, Norway
| | - Peng Lei
- National Institute of Occupational Health (STAMI), Oslo, Norway
| | - Pål Graff
- National Institute of Occupational Health (STAMI), Oslo, Norway
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Lee M, Vindenes HK, Fouladi F, Shigdel R, Ward JM, Peddada SD, London SJ, Bertelsen RJ. Oral microbiota related to allergy in Norwegian adults. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. GLOBAL 2025; 4:100435. [PMID: 40103748 PMCID: PMC11914992 DOI: 10.1016/j.jacig.2025.100435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 12/16/2024] [Accepted: 12/18/2024] [Indexed: 03/20/2025]
Abstract
Background Oral microbiome composition has been linked to onset and progression of several localized and systemic diseases. Associations with allergy in adults have been less explored. Objective We sought to identify oral microbiota associated with allergy outcomes in adults using high-throughput sequencing data. Methods We characterized bacterial communities of gingival samples from 453 Norwegian adults (average age, 28 years) using 16S rRNA gene amplicon sequencing. We examined more than 2200 bacterial taxa in relation to self-reported current asthma, eczema, or rhinitis, and seroatopy (IgE > 0.70 kU/L). We used linear regression to determine whether overall bacterial diversity differed by each allergic outcome and analysis of composition of microbiomes with bias correction (ANCOM-BC2) to identify differentially abundant taxa. Results Less diverse oral bacterial communities were observed (P < .05) in individuals with atopy or rhinitis compared with those without. Bacterial diversity did not differ by asthma and eczema status. While no bacterial taxa were differentially abundant by asthma, many were differentially abundant (P < .05 after multiple-testing correction) in relation to atopy, eczema, and rhinitis. These taxa include several from the genera Leptotrichia and Fusobacterium. Some, including Streptococcus, were previously implicated in respiratory health, whereas others were novel. We also found taxa related to nasal medication use in individuals with rhinitis. Notably, microbial network interconnections differed by allergy status. Conclusions Bacterial community compositions of oral gingival samples may play a role in allergic outcomes in adults. These findings could contribute to the development of novel treatment strategies.
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Affiliation(s)
- Mikyeong Lee
- Immunity Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC
| | - Hilde Kristin Vindenes
- Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Farnaz Fouladi
- Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC
| | - Rajesh Shigdel
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - James M Ward
- Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC
| | - Shayamal D Peddada
- Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC
| | - Stephanie J London
- Immunity Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC
| | - Randi Jacobsen Bertelsen
- Department of Clinical Science, University of Bergen, Bergen, Norway
- Oral Health Centre of Expertise in Western Norway-Vestland, Bergen, Norway
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Hernández-Trujillo PN, Lopez-Barón CA, Arévalo-Pinzón G, Trujillo-Güiza ML, González-Duque MI, Flórez AM, Franco DC, Vanegas J. Taxonomic and functional profile of the anorectal microbiota in HIV-positive and HIV-negative men who have sex with men, using a metagenomic approach. HIV Med 2025; 26:785-799. [PMID: 40098591 DOI: 10.1111/hiv.70014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 02/28/2025] [Indexed: 03/19/2025]
Abstract
INTRODUCTION The study of bacterial diversity in human samples is crucial for developing biomarkers of health and disease. This research characterized the taxonomic and functional diversity of the anorectal bacterial microbiota in men who hae sex with men (MSM) with HIV compared to men from this group without HIV. MATERIALS AND METHODS In July and August 2023, self-collected anorectal swabs were obtained. DNA was extracted from each sample, and metagenomic sequencing was performed. With the obtained data, alpha and beta diversity, bacterial abundance, differential operational taxonomic units, and functional diversity were determined. RESULTS Initially, 90 samples were collected, with 20 discarded due to having less than 200 ng of DNA and 15 due to incomplete sequencing, leaving 55 samples analysed (15 HIV-positive and 40 HIV-negative). No significant differences were found between groups in terms of alpha diversity (Shannon index p = 0.45) and beta diversity (PERMANOVA R = -0.03). Prevotella was identified as the most abundant genus in both groups. Twelve genes were found to be more abundant in the anorectal microbiota of the HIV group, which promote bacterial growth, colonization and survival. CONCLUSION Alterations in the anorectal microbiota could influence the pathogenesis of HIV and its complications in this population, underscoring the need to investigate these mechanisms and explore interventions to improve health. Longitudinal studies are needed to analyse changes in the anorectal microbiota during HIV infection and its response to treatment, integrating metagenomic, clinical, and immunological data to better understand the interactions between HIV, the microbiota and host health.
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Affiliation(s)
| | | | - Gabriela Arévalo-Pinzón
- Department of Microbiology, Faculty of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia
| | | | - Martha Isabel González-Duque
- Faculty of Medicine, Universidad Antonio Nariño - Circunvalar, Bogotá, Colombia
- Tissue Engineering Group, University of Applied Sciences and Arts Western Switzerland, Hepia, HES-SO, School of Landscape, Engineering, and Architecture of Geneva, Geneva, Switzerland
| | | | - Diego C Franco
- Department of Biology, Faculty of Sciences, Ghent University, Ghent, Belgium
| | - Javier Vanegas
- Faculty of Sciences, Universidad Antonio Nariño - Circunvalar, Bogotá, Colombia
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10
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Zhang X, Wu L, Gu L, Jiang Q, He Z, Qi Y, Zheng X, Xu T. Dietary areca nut extract supplementation modulates the growth performance and immunity of Jiaji ducks (Cairina moschata). Poult Sci 2025; 104:104971. [PMID: 40101514 PMCID: PMC11960628 DOI: 10.1016/j.psj.2025.104971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 02/21/2025] [Accepted: 02/28/2025] [Indexed: 03/20/2025] Open
Abstract
Areca nut extract (ANE) has a variety of pharmacological effects on animals. Here, we investigated the influence of ANE on the slaughter performance and immune function of Jiaji ducks. One hundred and fifty 42-day-old healthy Jiaji ducks were randomly divided into 2 groups (5 replicates of 15 ducks each), named DCK group (control) and DNT group (treatment), respectively. Ducks in the DCK group were fed a basal diet and ducks in the DNT group were fed a basal food supplemented with 0.08 g ANE per kg of basal diet. Additionally, using proteomics, untargeted metabolomics, and metagenomics, we analyzed the impact of ANE on the protein profile of the spleen, the composition of plasma metabolites, and the structure of the cecal microbiota. The results showed that the dietary inclusion of ANE significantly increased the slaughter rate of Jiaji ducks. Proteomic analysis revealed 78 differentially expressed proteins in the spleens of ANE-treated birds, including 54 proteins up-regulated and 24 proteins down-regulated in the DNT group, mainly enriched in cell adhesion molecules and glutathione metabolic pathways. Untargeted metabolomic analysis revealed that 117 serum metabolites were differentially regulated between the ANE and DCK groups; meanwhile, KEGG pathway analysis indicated that these metabolites were mainly involved in arachidonic acid metabolism, phospholipase D signaling pathway and eicosanoids. Furthermore, a metagenomic analysis showed that the genus Methanobrevibacter was significantly downregulated in the ANE supplementation group. Combined, the results of the metagenomic and metabolomic analyses showed that the relative abundance of Prevotella was significantly lower in the ANE group than in the DCK group and that Prevotella was negatively correlated with the levels of the anti-inflammatory compound hydrocinnamic acid and the lipid metabolism regulator ganoderic acid A. This study provides a reference for the application of ANE as a supplement in the diet of Jiaji ducks.
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Affiliation(s)
- Xiaohui Zhang
- College of Animal Science and Technology, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang, Henan 471003, China.
| | - Lehuan Wu
- College of Animal Science and Technology, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang, Henan 471003, China
| | - Lihong Gu
- Hainan Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Medicine, Haikou, Hainan 571100, China
| | - Qicheng Jiang
- Hainan Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Medicine, Haikou, Hainan 571100, China
| | - Zhongchun He
- Hainan Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Medicine, Haikou, Hainan 571100, China
| | - Yanxia Qi
- College of Animal Science and Technology, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang, Henan 471003, China
| | - Xinli Zheng
- Hainan Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Medicine, Haikou, Hainan 571100, China
| | - Tieshan Xu
- Chinese Academy of Tropical Agricultural Sciences, Institute of Tropical Crop Varieties Resources, Haikou, Hainan 571101, China
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11
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Ajith TA, Anita B. Impact of Gut Microbiota and Probiotics on Rheumatoid Arthritis: A Potential Treatment Challenge. Int J Rheum Dis 2025; 28:e70266. [PMID: 40329613 DOI: 10.1111/1756-185x.70266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 04/02/2025] [Accepted: 04/30/2025] [Indexed: 05/08/2025]
Abstract
Over the past few decades, there has been a surge in global study on the relationship between gut microbiota and human health. Numerous human illnesses have been linked to dysbiosis. Gram-positive firmicutes and Gram-negative bacteroidetes are the two leading bacterial phyla that make up 90% of the gut microbiome. Many symbionts in the gut environment establish intricate relationships with host defense to stop both local and non-native dangerous bacteria from colonizing and invading. Dysbiosis alters the paracellular route and damages the epithelium, enabling them to penetrate the epithelium and come into contact with the immune cells. Impaired intestinal barrier function, immune regulation mediated by metabolites derived from the gut microbiota, posttranslational modification of host proteins such as increased citrullination, regulation of the gut microbiota's effect on immune cells, intestinal epithelial cell autophagy, interaction between the microbiome and human leukocyte antigen alleles, and interaction with microRNAs are some of the mechanisms involved in rheumatoid arthritis (RA). The gut microbiota, Prevotella copri, and Collinsella spp. were shown to be higher in the early/preclinical phases of RA, while Bacteroidetes, Bifidobacteria, and Eubacterium rectale were found to be lower. Probiotic-based early dietary intervention may reduce inflammation and slow the rate of joint deterioration, and such intervention can also aid in the restoration of gut microbiota equilibrium. This review article describes the gut microbial dysbiosis and role of probiotics in RA.
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Affiliation(s)
| | - Bejoy Anita
- Department of General Medicine, Amala Institute of Medical Sciences, Thrissur, Kerala, India
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12
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Zhou X, Zhang T, Jia S, Xia S. Multi-omics analysis identifies Sphingomonas and specific metabolites as key biomarkers in elderly Chinese patients with coronary heart disease. Front Microbiol 2025; 16:1452136. [PMID: 40336827 PMCID: PMC12058083 DOI: 10.3389/fmicb.2025.1452136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 03/31/2025] [Indexed: 05/09/2025] Open
Abstract
Background Abnormal component changes of gut microbiota are related to the pathogenesis and progression of coronary heart disease (CHD), and gut microbiota-derived metabolites are key factors in host-microbiome interactions. This study aimed to explore the key gut microbiota and metabolites, as well as their relationships in CHD. Methods Feces samples and blood samples were collected from CHD patients and healthy controls. Then, the obtained feces samples were sent for 16s rRNA gene sequencing, and the blood samples were submitted for metabolomics analysis. Finally, conjoint analysis of 16s rRNA gene sequencing and metabolomics data was performed. Results After sequencing, there were no significant differences in Chao 1, observed species, Simpson, Shannon, Pielou's evenness and Faith's PD between the CHD patients and controls. At phylum level, the dominant phyla were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. At genus level, the abundance of Sphingomonas, Prevotella, Streptococcus, Desulfovibrio, and Shigella was relatively higher in CHD patients; whereas Roseburia, Corprococcus, and Bifidobacterium was relatively lower. Randomforest analysis showed that Sphingomonas was more important for CHD. Through metabolomic analysis, a total of 155 differential metabolites were identified, and were enriched in many signaling pathways. Additionally, the AUC of the conjoint analysis (0.908) was higher than that of gut microbiota species (0.742). Conclusion In CHD patients, the intestinal flora was disordered, as well as Sphingomonas and the identified differential metabolites may serve as was candidate biomarkers for CHD occurrence and progression.
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Affiliation(s)
- Xiaoshan Zhou
- Department of Critical Care Medicine, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China
| | - Tianlong Zhang
- Department of Critical Care Medicine, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China
| | - Sixiang Jia
- Department of Cardiology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China
| | - Shudong Xia
- Department of Cardiology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China
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13
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Zheng BX, Yi Y, Wang XW, Li CY, Zhao Y, Tian JZ, Wang LM, Han JY, Pan C, Liu SY, Liu CY, Qin SS, Tang X, Liu MT, Liang AH. Geniposide via enema alleviates colitis by modulating intestinal flora and bile acid metabolites, inhibiting S100A8/S100A9/NF-κB, and promoting TGR5 inhibition of NLRP3 inflammasome. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 142:156791. [PMID: 40279965 DOI: 10.1016/j.phymed.2025.156791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 03/12/2025] [Accepted: 04/19/2025] [Indexed: 04/29/2025]
Abstract
BACKGROUND Geniposide (GE) has potential efficacy in treating ulcerative colitis (UC). However, its reactivity can be affected by rapid degradation after oral administration. Furthermore, increasing oral doses may lead to hepatotoxicity. Thus, We used enema administration, characterized by smaller dose and higher localized concentration in the lesion, to improve the above situation. PURPOSE We aimed to confirm that enema administration is a better modality than oral administration for GE against UC and to explore its mechanism. STUDY DESIGN/METHOD We established UC mouse model, monitoring Disease Activity Index (DAI), inflammatory cytokines levels, and histopathology. Macrogenomics and bile acid (BAs) metabolomics analysed the major intestinal flora and BAs. Simultaneouslly, we conducted quantitative proteomics analysis and screened core proteins and pathway. In vitro validation was taken by qPCR, immunofluorescence and immunoblotting experiments. RESULTS GE via enema alleviate UC by inhibiting inflammatory factor production through downregulating S100A8/S100A9/NF-κB pathway. Analysis of the intestinal flora and BAs revealed that the enhanced abundance of Lachnospiraceae, which improves the ratio of primary to secondary BAs, and the reduced abundance of Provocaceae, which increases intestinal permeability and promotes inflammation, favored the restoration of the intestinal barrier. In addition, in vitro experiments confirmed that the key BA metabolites (mainly UDCA, DCA, and LCA) stimulated TGR5 signal to inhibit the assembly of the NLRP3 inflammasome and alleviated inflammation. CONCLUSION We firstly confirmed that GE alleviates UC via the enema route in a better manner than the oral route, through enhancing the intestinal barrier, restoring intestinal flora and BAs homeostasis, and inhibiting inflammatory injury. This study initially revealed that GE can alleviate UC through elevating UDCA, DCA, and LCA levels at the colonic site to activate TGR5 receptor for inhibiting the NLRP3 inflammasome, in addition to downregulating the S100A8/S100A9/-TLR4-NF-κB pathway related inflammatory response directly. The evidences offer a promising strategy and profround meaning for UC treatment.
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Affiliation(s)
- Bao-Xin Zheng
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Yan Yi
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Xing-Wen Wang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Chun-Ying Li
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Yong Zhao
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Jing-Zhuo Tian
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Lian-Mei Wang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Jia-Yin Han
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Chen Pan
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Su-Yan Liu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Chen-Yue Liu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Sha-Sha Qin
- Chongqing University Of Chinese Medicine, Chongging 400060, China.
| | - Xuan Tang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Mei-Ting Liu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Ai-Hua Liang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
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14
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Nemati MH, Yazdanpanah E, Kazemi R, Orooji N, Dadfar S, Oksenych V, Haghmorad D. Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential. BIOLOGY 2025; 14:435. [PMID: 40282300 PMCID: PMC12025160 DOI: 10.3390/biology14040435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/11/2025] [Accepted: 04/16/2025] [Indexed: 04/29/2025]
Abstract
Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the commensal microbiota, or dysbiosis, have been shown to affect immune homeostasis, leading to elevated levels of pro-inflammatory cytokines and disruption of the gut-brain axis. In this review, we provide a comprehensive overview of interactions between the gut microbiota and MS, especially focusing on the immunomodulatory actions of microbiota, such as influencing T-cell balance and control of metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., Prevotella and Faecalibacterium) were suggested to lay protective roles, whereas Akkermansia muciniphila was associated with disease aggravation. Interventions focusing on microbiota, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary therapies to normalize gut microbial homeostasis, suppress inflammation and are proven to improve clinical benefits in MS patients. Alterations in gut microbiota represent opportunities for identifying biomarkers for early diagnosis, disease progression and treatment response monitoring. Further studies need to be conducted to potentially address the interplay between genetic predispositions, environmental cues, and microbiota composition to get the precise mechanisms of the gut-brain axis in MS. In conclusion, the gut microbiota plays a central role in MS pathogenesis and offers potential for novel therapeutic approaches, providing a promising avenue for improving clinical outcomes in MS management.
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Affiliation(s)
- Mohammad Hosein Nemati
- Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, Iran
- Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran
| | - Esmaeil Yazdanpanah
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
| | - Roya Kazemi
- Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, Iran
- Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran
| | - Niloufar Orooji
- Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, Iran
- Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran
| | - Sepehr Dadfar
- Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, Iran
- Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran
| | - Valentyn Oksenych
- Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway
| | - Dariush Haghmorad
- Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran
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15
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Yu M, Lu Y, Zhang W, Gong X, Hao Z, Xu L, Wen Y, Dong X, Han F, Gao X. Preliminary analysis of salivary microbiota in catathrenia (nocturnal groaning) using machine learning algorithms. J Oral Microbiol 2025; 17:2489613. [PMID: 40247863 PMCID: PMC12004722 DOI: 10.1080/20002297.2025.2489613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 03/26/2025] [Accepted: 04/01/2025] [Indexed: 04/19/2025] Open
Abstract
Objectives The present study aimed to characterize the salivary microbiota in patients with catathrenia and to longitudinally validate potential biomarkers after treatment with mandibular advancement devices (MAD). Materials and methods Twenty-two patients with catathrenia (12 M/10 F, median age 28 y) and 22 age-matched control volunteers (8 M/14 F, median age 30 y) were included in the cross-sectional study. Video/audio polysomnography was conducted for diagnosis. All patients received treatment with custom-fit MAD and were followed for one month. Ten patients (6 M/4 F) underwent post-treatment PSG. Salivary samples were collected, and microbial characteristics were analyzed using 16S rRNA gene sequencing. The 10-fold cross-validated XGBoost and nested Random Forest Classifier machine learning algorithms were utilized to identify potential biomarkers. Results In the cross-sectional study, patients with catathrenia had lower α-diversity represented by Chao 1, Faith's phylogenetic diversity (pd), and observed species. Beta-diversity based on the Bray-Curtis dissimilarities revealed a significant inter-group separation (p = 0.001). The inter-group microbiota distribution was significantly different on the phylum and family levels. The treatment of MAD did not alter salivary microbiota distribution significantly. Among the most important genera in catathrenia and control classification identified by machine learning algorithms, four genera, Alloprevotella, Peptostreptococcaceae_XI_G1, Actinomyces and Rothia, changed significantly with MAD treatment. Correlation analysis revealed that Alloprevotella was negatively related to the severity of catathrenia (r2= -0.63, p < 0.001). Conclusions High-throughput sequencing revealed that the salivary microbiota composition was significantly altered in patients with catathrenia. Some characteristic genera (Alloprevotella, Peptostreptococcaceae_XI_G1, Actinomyces, and Rothia) could be potential biomarkers sensitive to treatment. Future studies are needed to confirm and determine the mechanisms underlying these findings.
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Affiliation(s)
- Min Yu
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China
- Center for Oral Therapy of Sleep Apnea, Peking University Hospital of Stomatology, Beijing, P.R. China
- National Center for Stomatology, Beijing, P.R. China
| | - Yujia Lu
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China
- Center for Oral Therapy of Sleep Apnea, Peking University Hospital of Stomatology, Beijing, P.R. China
- National Center for Stomatology, Beijing, P.R. China
| | - Wanxin Zhang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China
- Center for Oral Therapy of Sleep Apnea, Peking University Hospital of Stomatology, Beijing, P.R. China
- National Center for Stomatology, Beijing, P.R. China
| | - Xu Gong
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China
- Center for Oral Therapy of Sleep Apnea, Peking University Hospital of Stomatology, Beijing, P.R. China
- National Center for Stomatology, Beijing, P.R. China
| | - Zeliang Hao
- Department of Stomatology, Xuanwu Hospital, Capital Medical University, Beijing, P.R. China
| | - Liyue Xu
- Sleep Division, Peking University People’s Hospital, Beijing, P.R. China
| | - Yongfei Wen
- Sleep Division, Peking University People’s Hospital, Beijing, P.R. China
| | - Xiaosong Dong
- Sleep Division, Peking University People’s Hospital, Beijing, P.R. China
| | - Fang Han
- Sleep Division, Peking University People’s Hospital, Beijing, P.R. China
| | - Xuemei Gao
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China
- Center for Oral Therapy of Sleep Apnea, Peking University Hospital of Stomatology, Beijing, P.R. China
- National Center for Stomatology, Beijing, P.R. China
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16
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Vitari N, Roy S. Intestinal immunoglobulins under microbial dysbiosis: implications in opioid-induced microbial dysbiosis. Front Microbiol 2025; 16:1580661. [PMID: 40297286 PMCID: PMC12034684 DOI: 10.3389/fmicb.2025.1580661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 03/25/2025] [Indexed: 04/30/2025] Open
Abstract
Intestinal immunoglobulins (Igs) maintain homeostasis between the microbiome and host. IgA facilitates microbial balance through a variety of increasingly well-described mechanisms. However, IgM and IgG have less defined intestinal functions but have the potential to activate clearance mechanisms such as the complement system and receptor-mediated bacterial killing. Very little is known regarding the role of Igs under microbial dysbiosis. In this review, we explore how Igs sculpt the intestinal microbiome and respond to microbial dysbiosis. We discuss how IgM, IgA, IgG, and complement individually maintain harmony with the microbiome and consider how these mechanisms could work in synergy. Finally, we explore using an opioid-induced microbial dysbiosis as a model to elucidate immediate changes in Ig-bacterial interactions.
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Affiliation(s)
- Nicolas Vitari
- Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, United States
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Sabita Roy
- Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, United States
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, United States
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17
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Chattrakulchai K, Pongchaikul P, Wattanayingcharoenchai R, Tantitham C, Manonai J. Urinary microbiomes in postmenopausal women with or without urinary symptoms of the genitourinary syndrome of menopause: a cross-sectional study. Sci Rep 2025; 15:12796. [PMID: 40229501 PMCID: PMC11997101 DOI: 10.1038/s41598-025-97725-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 04/07/2025] [Indexed: 04/16/2025] Open
Abstract
Some postmenopausal women suffer from genital and urinary symptoms, while others do not. Therefore, the hypoestrogenic status cannot entirely explain the occurrence of the genitourinary syndrome in menopause (GSM). Differences in the urinary microbiome might play a role in bladder function and vulnerability to urinary symptoms. This study aimed to compare characterization urinary microbiome in postmenopausal women who experienced GSM with urinary symptoms with that in those without urinary symptoms. Forty participants were screened for genital symptoms of GSM and then divided into the urinary symptoms group and the non-urinary symptoms group on the basis of a validated questionnaire. 16 S rRNA gene sequencing was performed to investigate microbial diversity. The alpha diversity was used to evaluate the species richness and evenness, while the beta diversity was used to estimate the differences in the urinary microbiome between the groups. Differential abundance analysis was used to investigate biomarkers in the groups by linear discriminant analysis effect size. The relationship between the urinary microbiome and urinary symptoms was assessed using Spearman's correlation analysis. The characteristics of the participants were not different between the groups. Gardnerella was found in 22.2% (4/18) and 11.1% (2/18) of participants in the urinary symptoms group and in the non-urinary symptoms group, respectively (p > 0.05). Alpha diversity was less in the urinary symptoms group than in the non-urinary symptoms group, but this was not significant. Beta diversity of the urinary microbiome was not significantly different between the two groups. A differential abundance analysis showed that the genus Prevotella was significantly dominant in postmenopausal women with GSM who reported urinary symptoms. Prevotella was marginally correlated with voiding symptoms (r2 = 0.44; p = 0.01). The bladder or urinary microbiome is closely related to urinary symptoms of GSM. Species richness and diversity are not significantly different between postmenopausal women with GSM with and without urinary symptoms. Prevotella is dominant in symptomatic women and slightly correlated with voiding symptoms.
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Affiliation(s)
- Kitti Chattrakulchai
- Department of Obstetrics & Gynaecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Pisut Pongchaikul
- Ramathibodi Medical School, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 111 Bang Pla, Bang Phli, Samut Prakan, 10540, Thailand.
| | - Rujira Wattanayingcharoenchai
- Department of Obstetrics & Gynaecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Chananya Tantitham
- Department of Obstetrics & Gynaecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Jittima Manonai
- Department of Obstetrics & Gynaecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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18
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Mejia ME, Bowman S, Lee J, El-Halwagi A, Ferguson K, Maliekel M, Zhou Y, Serchejian C, Robertson CM, Ballard MB, Lu LB, Khan S, Oladunjoye OO, Huang S, Agarwal SK, Patras KA. A cross-sectional analysis of the vaginal microenvironment in rheumatoid arthritis. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2025.04.11.25325692. [PMID: 40297421 PMCID: PMC12036409 DOI: 10.1101/2025.04.11.25325692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
Objective The human microbiota is implicated in the development and progression of rheumatoid arthritis (RA). Given the increased RA burden in women, and well-known correlations between the vaginal microbiota and local inflammation, we seek to understand the vaginal microenvironment in the context of RA pathology. Methods Self-collected vaginal swabs and questionnaires on dietary and health practices were obtained from 36 RA and 50 demographically-matched control women, 18-63 years of age. Additionally, medication regimen and disease activity and severity were captured for the RA cohort. Vaginal swabs were subjected to full-length 16S rRNA gene sequencing, multiplex cytokine analyses, and quantification of rheumatoid factor, c-reactive protein, and anti-citrullinated protein antibodies (ACPAs). Results Vaginal microbial richness and genera Peptoniphilus and Prevotella, among other rare taxa, were elevated in RA versus control samples. Vaginal IL-18 and EGF levels were increased in the RA group; IL-18 correlated with multiple microbial features whereas EGF levels were not associated with bacterial composition or other host factors. Within the RA cohort, decreased relative abundance of Streptococcus was associated with joint pathologies, and Lactobacillus gasseri was lower in individuals with serum detection of ACPAs and rheumatoid factor. Vaginal ACPAs were higher in the RA group and positively correlated with Streptococcus and multiple vaginal inflammatory cytokines. Conclusions We describe vaginal microbial and immunological differences in women with RA, particularly when accounting for diet and menopausal status, disease activity and severity, and medication use. This work opens a new avenue in the multidisciplinary approach to RA patient care.
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Affiliation(s)
- Marlyd E. Mejia
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Savannah Bowman
- Section of Immunology, Allergy, and Rheumatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Jessica Lee
- Section of Immunology, Allergy, and Rheumatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Ali El-Halwagi
- Section of Immunology, Allergy, and Rheumatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Keshia Ferguson
- Section of Immunology, Allergy, and Rheumatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Maryjo Maliekel
- Section of Immunology, Allergy, and Rheumatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Yixuan Zhou
- Section of Immunology, Allergy, and Rheumatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Camille Serchejian
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Clare M. Robertson
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Mallory B. Ballard
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Lee B. Lu
- Section of General Internal Medicine, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Sobia Khan
- Section of General Internal Medicine, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Olubunmi O. Oladunjoye
- Section of General Internal Medicine, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Shixia Huang
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
| | - Sandeep K. Agarwal
- Section of Immunology, Allergy, and Rheumatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Kathryn A. Patras
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
- Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA
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19
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Xu J, Wu D, Yang J, Zhao Y, Liu X, Chang Y, Tang Y, Sun F, Zhao Y. Adult Outpatients with Long COVID Infected with SARS-CoV-2 Omicron Variant. Part 1: Oral Microbiota Alterations. Am J Med 2025; 138:732-741.e2. [PMID: 39151680 DOI: 10.1016/j.amjmed.2024.07.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 07/27/2024] [Accepted: 07/30/2024] [Indexed: 08/19/2024]
Abstract
BACKGROUND Many individuals experience long COVID after SARS-CoV-2 infection. As microbiota can influence health, it may change with COVID-19. This study investigated differences in oral microbiota between COVID-19 patients with and without long COVID. METHODS Based on a prospective follow-up investigation, this nested case-control study evaluated the differences in oral microbiota in individuals with and without long COVID (Symptomatic and Asymptomatic groups), which were assessed by 16S rRNA sequencing on tongue coating samples. A predictive model was established using machine learning based on specific differential microbial communities. RESULTS One-hundred-and-eight patients were included (n=54 Symptomatic group). The Symptomatic group had higher Alpha diversity indices (observed_otus, Chao1, Shannon, and Simpson indices), differences in microbial composition (Beta diversity), and microbial dysbiosis with increased diversity and relative abundance of pathogenic bacteria. Marker bacteria (c__Campylobacterota, o__Coriobacteriales, o__Pseudomonadales, and o__Campylobacterales) were associated with long COVID by linear discriminant analysis effect size and receiver operating characteristic curves (AUC 0.821). CONCLUSION There were distinct variations in oral microbiota between COVID-19 patients with and without long COVID. Changes in oral microbiota may indicate long COVID.
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Affiliation(s)
- Jianchao Xu
- Hebei University of Chinese Medicine, Shijiazhuang, China; Shijiazhuang People's Hospital, Shijiazhuang, China
| | - Di Wu
- Hebei University of Chinese Medicine, Shijiazhuang, China; The Traditional Chinese Medicine Hospital of Shijiazhuang, Shijiazhuang, China
| | - Jie Yang
- Hebei General Hospital, Shijiazhuang, China
| | - Yinuo Zhao
- Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Manchester, UK
| | - Xuzhao Liu
- Handan Hospital of Integrated Chinese and Western Medicine, Handan, China
| | - Yingying Chang
- The Traditional Chinese Medicine Hospital of Shijiazhuang, Shijiazhuang, China
| | - Yao Tang
- Wuhan Metware Biotechnology Co, Ltd, Wuhan, China
| | - Feng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Beijing, China
| | - Yubin Zhao
- Hebei University of Chinese Medicine, Shijiazhuang, China; Shijiazhuang People's Hospital, Shijiazhuang, China; Shijiazhuang College of Applied Technology, China.
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20
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Yang X, Che W, Zhang L, Zhang H, Chen X. Chronic airway inflammatory diseases and e-cigarette use: a review of health risks and mechanisms. Eur J Med Res 2025; 30:223. [PMID: 40170170 PMCID: PMC11959776 DOI: 10.1186/s40001-025-02492-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Accepted: 03/21/2025] [Indexed: 04/03/2025] Open
Abstract
Chronic airway inflammatory diseases, which primarily include chronic obstructive pulmonary disease (COPD), asthma, allergic rhinitis, and chronic sinusitis, continue to have a high global prevalence, highlighting their significant public health impact. Concurrently, the use of e-cigarettes (tobacco e-cigarettes) has been rising worldwide, with many users perceiving them as a safer alternative to traditional cigarettes. However, accumulating evidence from international studies suggests that e-cigarettes pose substantial health risks. This review aims to explore recent research on the relationship between e-cigarette use and chronic airway inflammatory diseases. The findings indicate that e-cigarette usage increases the risk of developing these conditions. Specifically, studies have shown that e-cigarettes exacerbate airway inflammatory responses, elevate levels of type 2 inflammatory cytokines such as IL-4, IL-5, and IL-13, increase cellular oxidative stress, and impair lung function. These mechanisms may collectively contribute to an increased risk of chronic airway inflammatory diseases potentially associated with e-cigarette use.
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Affiliation(s)
- Xing Yang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Wenqi Che
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Lu Zhang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Huanping Zhang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China.
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, China.
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Xiaoxue Chen
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, China.
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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21
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Wu J, Zhang X, Ayesha K, Khuram S, Cui J, Wang G, Yangzong Z, Shi M, Jiang X, Li L, Liu G, Zhao W, Song T. Multi-omics analysis of the mechanism of alfalfa and wheat-induced rumen flatulence in Xizang sheep. Microbiol Spectr 2025; 13:e0326824. [PMID: 40052788 PMCID: PMC11960438 DOI: 10.1128/spectrum.03268-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Accepted: 01/26/2025] [Indexed: 04/03/2025] Open
Abstract
Rumen flatulence is a diet-related rumen disease in ruminants. This study induced a rumen flatulence model in Xizang sheep using alfalfa (HRF) and wheatgrass (MRF). The aim was to understand the rumen microbiota diversity in healthy and pathological states, host-microbiota interactions, and the molecular mechanisms of rumen flatulence. Results showed that the pH in the HRF and MRF groups was lower than that in the natural grass group (LRF). SCFA concentrations varied between groups: in HRF, 2-BA and CA increased; in MRF, 4-MVA and 5-MCA rose. Microbial analysis indicated that the alpha- and beta-diversity of HRF and MRF groups were lower than LRF's, with different microbial compositions. Transcriptome analysis revealed many differentially expressed genes (DEGs). Compared to MRF, HRF had 348 upregulated and 511 downregulated DEGs. Versus LRF, MRF had 201 upregulated and 185 downregulated DEGs, while HRF had 128 upregulated and 238 downregulated DEGs. Spearman's correlation analysis showed that there was a positive correlation between Butyrivibrio, Quinella, and specific genes. These findings reveal the potential mechanism of rumen flatulence in Xizang sheep and provide new insights into the prevention and treatment of the disease.IMPORTANCEThe research used a high-protein diet to induce a model to understand the diversity of rumen microbiota and its interaction with the host, as well as exploring the molecular mechanisms of rumen flatulence.
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Affiliation(s)
- Jing Wu
- Institute of Animal Science, Xizang Academy of Agricultural and Animal Husbandry Science, Lhasa, Xizang, China
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Xiaoming Zhang
- Institute of Animal Science, Xizang Academy of Agricultural and Animal Husbandry Science, Lhasa, Xizang, China
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Khan Ayesha
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Shahzad Khuram
- Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS University Islamabad (CUI), Lahore, Pakistan
| | - Jianzhao Cui
- Institute of Animal Science, Xizang Academy of Agricultural and Animal Husbandry Science, Lhasa, Xizang, China
- Shigatse Science Popularization Center, Shigatse, Xizang, China
| | - Gaofu Wang
- Chongqing Academy of Animal Science, Chongqing, China
| | - Zhaxi Yangzong
- Institute of Animal Science, Xizang Academy of Agricultural and Animal Husbandry Science, Lhasa, Xizang, China
| | - Mingyan Shi
- College of Life Science, Luoyang Normal University, Luoyang, Henan, China
| | - Xunping Jiang
- College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Long Li
- Institute of Animal Science, Xizang Academy of Agricultural and Animal Husbandry Science, Lhasa, Xizang, China
| | - Guiqiong Liu
- College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Wangsheng Zhao
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Tianzeng Song
- Institute of Animal Science, Xizang Academy of Agricultural and Animal Husbandry Science, Lhasa, Xizang, China
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
- College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China
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22
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Li D, Meng K, Liu G, Wen Z, Han Y, Liu W, Xu X, Song L, Cai H, Yang P. Lactiplantibacillus plantarum FRT4 protects against fatty liver hemorrhage syndrome: regulating gut microbiota and FoxO/TLR-4/NF-κB signaling pathway in laying hens. MICROBIOME 2025; 13:88. [PMID: 40158133 PMCID: PMC11954192 DOI: 10.1186/s40168-025-02083-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 03/08/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Fatty liver hemorrhage syndrome (FLHS) has become one of the major factors leading to the death of laying hen in caged egg production. FLHS is commonly associated with lipid peroxidation, hepatocyte injury, decreased antioxidant capacity, and inflammation. However, there are limited evidences regarding the preventive effect of Lactiplantibacillus plantarum on FLHS in laying hens and its mechanisms. Our previous results showed that Lp. plantarum FRT4 alleviated FLHS by regulating lipid metabolism, but did not focus on its antioxidant and anti-inflammatory functions and mechanisms. Therefore, this study aimed to investigate the preventive mechanisms of Lp. plantarum FRT4 in alleviating FLHS, with a focus on its role in antioxidant activity and inflammation regulation. RESULTS Supplementation with Lp. plantarum FRT4 enhanced the levels of T-AOC, T-SOD, and GSH-Px, while reducing the levels of TNF-α, IL-1β, IL-8, and NLRP3 in the liver and ovary of laying hens. Additionally, Lp. plantarum FRT4 upregulated the mRNA expressions of SOD1, SOD2, CAT, and GPX1, downregulated the mRNA expressions of pro-inflammatory factors IL-1β, IL-6, and NLRP3, and upregulated the mRNA expressions of anti-inflammatory factors IL-4 and IL-10. Lp. plantarum FRT4 improved the structure and metabolic functions of gut microbiota, and regulated the relative abundances of dominant phyla (Bacteroidetes, Firmicute, and Proteobacteria) and genera (Prevotella and Alistipes). Additionally, it influenced key KEGG pathways, including tryptophan metabolism, amino sugar and nucleotide sugar metabolism, insulin signaling pathway, FoxO signaling pathway. Spearman analysis revealed that the abundance of microbiota at different taxonomic levels was closely related to antioxidant enzymes and inflammatory factors. Furthermore, Lp. plantarum FRT4 modulated the mRNA expressions of related factors in the FoxO/TLR-4/NF-κB signaling pathway by regulating gut microbiota. Moreover, the levels of E2, FSH, and VTG were significantly increased in the ovary after Lp. plantarum FRT4 intervention. CONCLUSIONS Lp. plantarum FRT4 effectively ameliorates FLHS in laying hens. This efficacy is attributed to its antioxidant and anti-inflammatory properties, which are mediated by modulating the structure and function of gut microbiota, and further intervening in the FoxO/TLR-4/NF-κB signaling pathway. These actions enhance hepatic and ovarian function and increase estrogen levels. Video Abstract.
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Affiliation(s)
- Daojie Li
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Kun Meng
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Guohua Liu
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Zhiguo Wen
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Yunsheng Han
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Weiwei Liu
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Xin Xu
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Liye Song
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Hongying Cai
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.
| | - Peilong Yang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.
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23
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Ma B, Barathan M, Ng MH, Law JX. Oxidative Stress, Gut Microbiota, and Extracellular Vesicles: Interconnected Pathways and Therapeutic Potentials. Int J Mol Sci 2025; 26:3148. [PMID: 40243936 PMCID: PMC11989138 DOI: 10.3390/ijms26073148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 03/26/2025] [Accepted: 03/27/2025] [Indexed: 04/18/2025] Open
Abstract
Oxidative stress (OS) and gut microbiota are crucial factors influencing human health, each playing a significant role in the development and progression of chronic diseases. This review provides a comprehensive analysis of the complex interplay between these two factors, focusing on how an imbalance between reactive oxygen species (ROS) and antioxidants leads to OS, disrupting cellular homeostasis and contributing to a range of conditions, including metabolic disorders, cardiovascular diseases, neurological diseases, and cancer. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, is essential for regulating immune responses, metabolic pathways, and overall health. Dysbiosis, an imbalance in the gut microbiota composition, is closely associated with chronic inflammation, metabolic dysfunction, and various diseases. This review highlights how the gut microbiota influences and is influenced by OS, complicating the pathophysiology of many conditions. Furthermore, emerging evidence has identified extracellular vesicles (EVs) as critical facilitators of cellular crosstalk between the OS and gut microbiota. EVs also play a crucial role in signaling between the gut microbiota and host tissues, modulating immune responses, inflammation, and metabolic processes. The signaling function of EVs holds promise for the development of targeted therapies aimed at restoring microbial balance and mitigating OS. Personalized therapeutic approaches, including probiotics, antioxidants, and fecal microbiota transplantation-based strategies, can be used to address OS-related diseases and improve health outcomes. Nonetheless, further research is needed to study the molecular mechanisms underlying these interactions and the potential of innovative interventions to offer novel strategies for managing OS-related diseases and enhancing overall human health.
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Affiliation(s)
| | | | | | - Jia Xian Law
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; (B.M.); (M.B.); (M.H.N.)
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24
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Onwusereaka CO, Jalaludin J, Oluchi SE, Poh Choo VC. New generation sequencing: molecular approaches for the detection and monitoring of bioaerosols in an indoor environment: a systematic review. REVIEWS ON ENVIRONMENTAL HEALTH 2025; 40:47-62. [PMID: 38214730 DOI: 10.1515/reveh-2023-0004] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 12/14/2023] [Indexed: 01/13/2024]
Abstract
INTRODUCTION The exposure of occupants to indoor air pollutants has increased in recent decades. The aim of this review is to discuss an overview of new approaches that are used to study fungal aerosols. Thus, this motivation was to compensate the gaps caused by the use of only traditional approaches in the study of fungal exposure. CONTENT The search involved various databases such as; Science Direct, PubMed, SAGE, Springer Link, EBCOHOST, MEDLINE, CINAHL, Cochrane library, Web of Science and Wiley Online Library. It was limited to full text research articles that reported the use of non-viable method in assessing bioaerosol, written in English Language, full text publications and published from year 2015-2022. SUMMARY AND OUTLOOK A total of 15 articles met the inclusion criteria and was included in this review. The use of next-generation sequencing, which is more commonly referred to as high-throughput sequencing (HTS) or molecular methods in microbial studies is based on the detection of genetic material of organisms present in a given sample. Applying these methods to different environments permitted the identification of the microorganisms present, and a better comprehension of the environmental impacts and ecological roles of microbial communities. Based on the reviewed articles, there is evidence that dust samples harbour a high diversity of human-associated bacteria and fungi. Molecular methods such as next generation sequencing are reliable tools for identifying and tracking the bacterial and fungal diversity in dust samples using 18S metagenomics approach.
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Affiliation(s)
- Cynthia Oluchi Onwusereaka
- Department of Environmental and Occupational Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Selangor, Malaysia
| | - Juliana Jalaludin
- Department of Environmental and Occupational Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Selangor, Malaysia
| | - Sampson Emilia Oluchi
- Department of Community Health, Faculty of Medicine and Health Science, Universiti Putra Malaysia Serdang, Selangor, Malaysia
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25
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Sasahira M, Matsumoto H, Go TT, Yo S, Monden S, Ninomiya T, Oosawa M, Handa O, Umegaki E, Inoue R, Shiotani A. The Relationship Between Bacterial Flora in Saliva and Esophageal Mucus and Endoscopic Severity in Patients with Eosinophilic Esophagitis. Int J Mol Sci 2025; 26:3026. [PMID: 40243638 PMCID: PMC11989152 DOI: 10.3390/ijms26073026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/15/2025] [Accepted: 03/22/2025] [Indexed: 04/18/2025] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by esophageal dysfunction and eosinophilic inflammation of the esophageal mucosa. In this study, we investigated the bacterial flora in saliva and esophageal mucus in patients with EoE and examined the relationship between EoE disease activity and mucosal cytokine expression, involving patients with active and inactive EoE (A-EoE and I-EoE, respectively). A-EoE was defined as a peak eosinophil count > 15/high-power field, according to the 2025 consensus guidelines. Saliva samples were collected from patients before the endoscopic examination. Brushing samples were collected from the distal esophagus of patients with EoE during endoscopic procedures. The degree of EoE inflammation was assessed using the EoE endoscopic reference score (EREFS). The samples were profiled using the Illumina MiSeq platform. The V3-V4 regions of the 16S rRNA gene (460 bp) were amplified using tailed PCR. Fifty-nine patients were enrolled, including eight with I-EoE, seventeen with A-EoE, and twenty-eight non-EoE controls. Major bacterial genera such as Streptococcus, Prevotella, Veillonella, and Haemophilus were detected in both the oral cavity and esophagus. Compared with the control group, the active EoE group had significantly more Prevotella spp. in the saliva and esophageal mucosa. Conversely, significantly fewer Neisseria spp. were found in the saliva and Streptococcus spp. in the esophageal mucosa of patients with active EoE. The EREFS of EoE and Streptococcus were inversely correlated. This study elucidated the characteristics of bacterial flora in the saliva and esophageal mucosa of patients with EoE.
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Affiliation(s)
- Momoyo Sasahira
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (S.M.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Hiroshi Matsumoto
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (S.M.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Tei Tei Go
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (S.M.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Shogen Yo
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (S.M.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Shuzo Monden
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (S.M.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Takahirao Ninomiya
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (S.M.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Motoyasu Oosawa
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (S.M.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Osamu Handa
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (S.M.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Eiji Umegaki
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (S.M.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Ryo Inoue
- Faculty of Agriculture, Setsunan University, Hirakata-City 573-0101, Japan;
| | - Akiko Shiotani
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (S.M.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
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26
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Chen G, Li Y, Wei S, Wang X, Kuang Z, Guo W, Qin J, Huang T, Li Y, Zhu C. Role of gut microbiota in thalassemia: a review of therapeutic prospects. Front Physiol 2025; 16:1523448. [PMID: 40177354 PMCID: PMC11962020 DOI: 10.3389/fphys.2025.1523448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 03/05/2025] [Indexed: 04/05/2025] Open
Abstract
In recent years, the study of gut microbiota has gradually become a research hotspot in the field of medicine, as gut microbiota dysbiosis is closely related to various diseases. Thalassemia, as a hereditary hemoglobinopathy, has a complex pathophysiological mechanism, and traditional treatment methods show limited efficacy. With a deeper understanding of the gut microbiome, researchers have begun to focus on its role in the pathogenesis of thalassemia and its therapeutic effects. This article aims to review the role of gut microbiota in thalassemia and its potential therapeutic prospects, analyze the latest research findings, and explore the impact and mechanisms of gut microbiota on patients with thalassemia, with the goal of providing new ideas and directions for future research and clinical treatment of thalassemia.
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Affiliation(s)
- Guanjun Chen
- Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China
| | - Yulan Li
- Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China
| | - Shirui Wei
- Shandong Second Medical University, Weifang, Shandong, China
| | - Xinyu Wang
- Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China
| | - Zheshu Kuang
- Chenzhou Third People’s Hospital (Group), Chenzhou, Hunan, China
| | - Weiming Guo
- Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China
| | - Jianbin Qin
- Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China
| | - Tianjun Huang
- Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China
| | - Youlin Li
- Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China
| | - Chunjiang Zhu
- Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China
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27
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Hu W, Zhou S, Ibrahim A, Li G, Awad S, Ramos-Vivas J, Kan J, Du M. Whole Genome Analysis of Pediococcus acidilactici XJ-24 and Its Role in Preventing Listeria monocytogenes ATCC ® 19115 TM Infection in C57BL/6 Mice. Antibiotics (Basel) 2025; 14:323. [PMID: 40149133 PMCID: PMC11939717 DOI: 10.3390/antibiotics14030323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 03/12/2025] [Accepted: 03/17/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives: As probiotics gain prominence in the prevention and treatment of intestinal diseases, their protective effects against pathogens and influence on host health have drawn significant attention. This study investigates the genomic characteristics and functional potential of Pediococcus acidilactici XJ-24 (XJ-24) in the prevention of Listeria monocytogenes (LM) infection in mice. Methods/Results: Whole-genome analysis confirmed the safety and probiotic properties of XJ-24, including acid and bile salt tolerance, antimicrobial activity, and safety. In vivo, C57BL/6 mice challenges indicated that XJ-24 significantly reduced LM colonization, suppressed pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-γ), alleviated colon and spleen tissue damage, and maintained intestinal barrier integrity by upregulating tight junction proteins (Occludin, Claudin-1, ZO-1). Moreover, XJ-24 modulated gut microbiota composition by increasing beneficial taxa while reducing harmful bacteria. Correlation analysis highlighted a positive association between Lachnospiraceae and tight junction proteins. Conclusions: These findings demonstrate the potential of XJ-24 as a functional probiotic for preventing LM infection and provide a basis for further clinical exploration.
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Affiliation(s)
- Weizhong Hu
- College of Food Science, Southwest University, Chongqing 400715, China; (W.H.); (S.Z.); (J.K.)
- Chinese-Hungarian Cooperative Research Center for Food Science, Southwest University, Chongqing 400715, China
- Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and Chongqing, Chongqing 400715, China
| | - Shuxin Zhou
- College of Food Science, Southwest University, Chongqing 400715, China; (W.H.); (S.Z.); (J.K.)
- Chinese-Hungarian Cooperative Research Center for Food Science, Southwest University, Chongqing 400715, China
- Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and Chongqing, Chongqing 400715, China
| | - Amel Ibrahim
- Faculty of Agriculture, Alexandria University, Alexandria 21500, Egypt; (A.I.); (S.A.)
| | - Guannan Li
- College of Sericulture, Textile and Biomass, Southwest University, Chongqing 400716, China;
| | - Sameh Awad
- Faculty of Agriculture, Alexandria University, Alexandria 21500, Egypt; (A.I.); (S.A.)
| | - José Ramos-Vivas
- Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, 39011 Santander, Spain;
| | - Jianquan Kan
- College of Food Science, Southwest University, Chongqing 400715, China; (W.H.); (S.Z.); (J.K.)
- Chinese-Hungarian Cooperative Research Center for Food Science, Southwest University, Chongqing 400715, China
- Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and Chongqing, Chongqing 400715, China
| | - Muying Du
- College of Food Science, Southwest University, Chongqing 400715, China; (W.H.); (S.Z.); (J.K.)
- Chinese-Hungarian Cooperative Research Center for Food Science, Southwest University, Chongqing 400715, China
- Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and Chongqing, Chongqing 400715, China
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Yang CC, Washio J, Lin YC, Hsu ML, Wang DH, Tsai FT, Lin YM, Tu HF, Chang HC, Takahashi N. Microbiome Signatures and Dysbiotic Patterns in Oral Cancer and Precancerous Lesions. Oral Dis 2025. [PMID: 40106821 DOI: 10.1111/odi.15317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 01/24/2025] [Accepted: 03/10/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND The oral microbiome has been shown to be associated with the development of oral squamous cell carcinoma (OSCC). Research has primarily focused on elucidating the oncogenic mechanisms of specific pathogens by comparing the microbiomes of OSCC and normal tissues. However, the characteristics of the microbiome in the precancerous state remain less understood, as does the influence of metabolic and environmental factors on OSCC-associated microbiomes. METHODS In this study, we analyzed mucosa-associated microbiomes in normal, precancerous, and OSCC lesions from a cohort of 51 patients using 16S rRNA amplicon sequencing. We investigated compositional changes in the microbiome, including the specific abundances and co-occurrences of OSCC-associated bacteria. RESULTS Our findings indicate that the microbiome associated with precancerous lesions is indistinguishable from that of the normal mucosa, whereas the OSCC microbiome significantly differs from both normal and precancerous conditions. Specifically, the OSCC microbiome harbors less Streptococcus, coupled with an increase in amino-acid-degrading anaerobes such as Fusobacterium and Prevotella. The metabolic properties of individual microbes reported suggest that the overrepresentation of OSCC-specific bacteria is a result of metabolic adaptation to tumor microenvironments, although this possibility needs to be experimentally confirmed. CONCLUSIONS Our results demonstrate oral microbiome patterns across OSCC progression, offering insights into microbial ecological perspectives.
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Affiliation(s)
- Cheng-Chieh Yang
- Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Stomatology, Oral & Maxillofacial Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jumpei Washio
- Division of Oral Ecology and Biochemistry, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Yu-Cheng Lin
- Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Oral Medicine Innovation Center (OMIC), National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ming-Lun Hsu
- Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ding-Han Wang
- Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Oral Medicine Innovation Center (OMIC), National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Fa-Tzu Tsai
- Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yu-Min Lin
- Institute of Oral Biology, School of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Hsi-Feng Tu
- Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Dentistry, National Yang Ming Chiao Tung University Hospital, Yilan County, Taiwan
| | - Hsiu-Chuan Chang
- Institute of Oral Biology, School of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Nobuhiro Takahashi
- Division of Oral Ecology and Biochemistry, Tohoku University Graduate School of Dentistry, Sendai, Japan
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Lim DM, Kim D, Ju HM, Jeong SH, Kim YH, Ok SM, Park HR. Distinct Immunological Features Compared to Lichen Planus and Oral Lichen Planus. J Inflamm Res 2025; 18:4037-4056. [PMID: 40125076 PMCID: PMC11929516 DOI: 10.2147/jir.s506313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 03/05/2025] [Indexed: 03/25/2025] Open
Abstract
Purpose Lichen planus (LP) and oral lichen planus (OLP) share clinical and histological similarities, yet their distinct immunopathological mechanisms make differentiation and management challenging. Clarifying these differences is essential for accurate diagnosis and treatment. This study aimed to investigate the systemic immune profile of OLP using single-cell transcriptomics, identifying distinct immune cell subsets and signaling pathways contributing to its chronic inflammatory state. Additionally, it sought to compare the inflammatory lesion microenvironments of OLP and LP by analyzing key immune pathways and cellular interactions. Methods Peripheral blood mononuclear cells (PBMCs) were obtained from 16 OLP patients and 5 healthy controls. Single-cell transcriptomic data from PBMCs and lesion tissues of OLP and LP were analyzed to profile immune and inflammatory signatures. Key molecular findings were validated using independent datasets and enzyme-linked immunosorbent assays (ELISA). Results Prostaglandin D2 synthase (PTGDS), a pivotal enzyme in prostaglandin metabolism, emerged as a diagnostic marker with elevated expression in NK cells from OLP patients. Additionally, a novel CXCR4 high-TSC22D3 high CD4 cytotoxic T cell subset with enhanced cytotoxicity was identified, potentially contributing to OLP pathogenesis. OLP blood samples also demonstrated significant upregulation of TNF and TLR signaling in NK cells, indicating a heightened chronic inflammatory state. Comparative tissue analysis revealed intensified TNF-driven inflammation and a disrupted HIF1A- vascular endothelial growth factor (VEGF) interactions in OLP, contrasting with LP's robust VEGF-mediated angiogenesis. Discussion These findings highlight distinct immunopathogenic mechanisms between OLP and LP. The upregulation of PTGDS in NK cells and CXCR4 high-TSC22D3 high CD4 cytotoxic T cells in PBMCs indicates systemic immune dysregulation in OLP, while tissue-level differences suggest impaired vascular remodeling and chronic inflammation. These insights underscore the need for targeted immunomodulatory therapies. Conclusion This study identifies distinct immune signatures that differentiate OLP from LP, highlighting potential therapeutic targets that require further validation for personalized treatment strategies.
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Affiliation(s)
- Dong Min Lim
- Interdisciplinary Program of Genomic Data Science, Pusan National University, Yangsan, 50612, Republic of Korea
| | - DoYeon Kim
- Department of Oral Pathology, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea
| | - Hye-Min Ju
- Department of Oral Medicine, Dental and Life Science Institute, Pusan National University School of Dentistry, Yangsan, 50612, Republic of Korea
- Department of Oral Medicine, Dental Research Institute, Pusan National University Dental Hospital, Yangsan, 50612, Republic of Korea
| | - Sung-Hee Jeong
- Department of Oral Medicine, Dental and Life Science Institute, Pusan National University School of Dentistry, Yangsan, 50612, Republic of Korea
- Department of Oral Medicine, Dental Research Institute, Pusan National University Dental Hospital, Yangsan, 50612, Republic of Korea
| | - Yun Hak Kim
- Periodontal Disease Signaling Network Research Center, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea
- Department of Anatomy, School of Medicine, Pusan National University, Yangsan, 50612, Republic of Korea
- Department of Biomedical Informatics, School of Medicine, Pusan National University, Yangsan, 50612, Republic of Korea
| | - Soo-Min Ok
- Department of Oral Medicine, Dental and Life Science Institute, Pusan National University School of Dentistry, Yangsan, 50612, Republic of Korea
- Department of Oral Medicine, Dental Research Institute, Pusan National University Dental Hospital, Yangsan, 50612, Republic of Korea
| | - Hae Ryoun Park
- Department of Oral Pathology, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea
- Periodontal Disease Signaling Network Research Center, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea
- Department of Periodontology and Dental Research Institute, Pusan National University Dental Hospital, Yangsan, 50612, Republic of Korea
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Monari B, Wilcox H, Haywood P, Gajer P, Rojas-Vargas J, Zuanazzi D, Rutt L, Shouldice A, Parmar R, Waetjen LE, Krakowsky Y, Potter E, Prodger JL, Ravel J. The vaginal microbiota, symptoms, and local immune correlates in transmasculine individuals using sustained testosterone therapy. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.03.14.643255. [PMID: 40161595 PMCID: PMC11952554 DOI: 10.1101/2025.03.14.643255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Transmasculine individuals (assigned female at birth, masculine gender identity, TM) may use gender-affirming testosterone therapy, and some TM report adverse genital symptoms during treatment. In cis women, the vaginal microbiota is a key determinant of reproductive and sexual health outcomes; Lactobacillus-dominant communities are considered optimal, while more even, diverse, Lactobacillus-depleted microbiota are considered non-optimal. Prior studies suggest Lactobacillus deficiency in TM vaginal microbiota, but associations with symptoms and immune markers remain unclear. We launched the TransBiota study to characterize the TM vaginal microbiota, soluble mediators of local inflammation (SMI), and self-reported symptoms over three weeks. Fewer than 10% of TM possessed Lactobacillus-dominant microbiota, and most exhibited more diverse, Lactobacillus-depleted microbiota. We identified 11 vaginal microbiota community state types (tmCSTs), with Lactobacillus-dominant tmCSTs unexpectedly linked to abnormal odor and elevated IL-1α. These findings indicate that Lactobacillus dominance may no longer be an optimal state for TM during gender-affirming testosterone therapy and change in clinical management is needed.
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Affiliation(s)
- Bern Monari
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Hannah Wilcox
- Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Priscilla Haywood
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Pawel Gajer
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Jorge Rojas-Vargas
- Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
- Department of Biology, Western University, London, ON, Canada
| | - David Zuanazzi
- Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Lindsay Rutt
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Ainslie Shouldice
- Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Reeya Parmar
- Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - L. Elaine Waetjen
- Department of Obstetrics and Gynecology, University of California Davis, Sacramento, CA, USA
| | - Yonah Krakowsky
- Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada
- Transition Related Surgery, Department of Surgery, Women’s College Hospital, University of Toronto, Toronto, ON, Canada
- Division of Urology, Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Emery Potter
- Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada
- Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada
| | - Jessica L. Prodger
- Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
- Department of Biology, Western University, London, ON, Canada
| | - Jacques Ravel
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA
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Fan K, Hua X, Wang S, Efferth T, Tan S, Wang Z. A promising fusion: Traditional Chinese medicine and probiotics in the quest to overcome osteoporosis. FASEB J 2025; 39:e70428. [PMID: 40047492 DOI: 10.1096/fj.202403209r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/23/2025] [Accepted: 02/19/2025] [Indexed: 05/13/2025]
Abstract
Botanical drugs and probiotic supplements present safer alternative options for the prevention and treatment of osteoporosis (OP). However, pathological disorders of the gut microbiota and the specific properties of probiotics and traditional Chinese medicine (TCM) significantly limit their therapeutic efficacy. Given the favorable synergistic and complementary effects between probiotics and herbal medicines, a creative combination of these approaches may address the issue of their current limited efficacy. A comprehensive analysis is necessary to provide a detailed review of their potential for combination, the mechanisms behind their synergy, scientific applications, and future developments. There exists a complex relationship between gut microbiota and OP, and the underlying regulatory mechanisms are multidimensional, involving the production of pro-inflammatory metabolites, immune system disruption, and the impairment of the intestinal mucosal barrier. Furthermore, we analyzed the complex mechanisms and potential connections between probiotics, TCM, and their combined applications. We highlighted the principle of complementary gain and the substantial therapeutic potential of their organic combination, which facilitates the release of active substances in TCM, increases the bioavailability of TCM, enhances probiotic delivery efficiency, and exerts synergistic effects. The combined use of probiotics and TCM offers a safe and effective strategy for managing OP and presents an innovative and promising direction for the future development of modern phytomedicine.
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Affiliation(s)
- Kangcheng Fan
- College of Exercise and Health, Shenyang Sport University, Shenyang, China
| | - Xin Hua
- Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, China
| | - Shuwan Wang
- College of Exercise and Health, Shenyang Sport University, Shenyang, China
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | - Shengnan Tan
- Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, China
| | - Zhuo Wang
- College of Exercise and Health, Shenyang Sport University, Shenyang, China
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Ravenda S, Mancabelli L, Gambetta S, Barbetti M, Turroni F, Carnevali L, Ventura M, Sgoifo A. Heart rate variability, daily cortisol indices and their association with psychometric characteristics and gut microbiota composition in an Italian community sample. Sci Rep 2025; 15:8584. [PMID: 40074815 PMCID: PMC11903775 DOI: 10.1038/s41598-025-93137-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 03/05/2025] [Indexed: 03/14/2025] Open
Abstract
The microbiota-gut-brain axis is a complex communication system that plays a crucial role in influencing various aspects of our physical and mental health. The goal of this study was to determine the extent to which individual differences in resting measures of vagally-mediated heart rate variability (HRV) and cortisol levels were associated with psychometric and specific gut microbiota characteristics in seventy-five (38 females) healthy individuals. Participants were assessed for vagally-mediated HRV, daily salivary cortisol levels, psychometric characteristics, and gut microbiota composition. Using a categorical approach based on the median split of HRV and cortisol values, we identified an association between low vagally-mediated HRV, greater depressive symptomatology, and altered gut microbiota (e.g., a higher abundance of Prevotella and a smaller abundance of Faecalibacterium, Alistipes, and Gemmiger). This suggests that vagally-mediated HRV may be a useful biomarker of microbiota-gut brain axis function, and that low vagally-mediated HRV may play an important role in the bidirectional link between gut dysbiosis and depression. On the other hand, daily cortisol parameters (e.g., cortisol awakening response, diurnal cortisol slope) were associated either with higher anxiety and perceived stress, or with a specific gut microbiota profile. Therefore, their utility as biomarkers of microbiota-gut-brain axis function needs further scrutiny.
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Affiliation(s)
- Sebastiano Ravenda
- Department of Chemistry, Life Sciences and Environmental Sustainability, Stress Physiology Lab, University of Parma, Parma, Italy
| | - Leonardo Mancabelli
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Microbiome Research Hub, University of Parma, Parma, Italy
| | - Sara Gambetta
- Department of Chemistry, Life Sciences and Environmental Sustainability, Stress Physiology Lab, University of Parma, Parma, Italy
| | - Margherita Barbetti
- Department of Chemistry, Life Sciences and Environmental Sustainability, Stress Physiology Lab, University of Parma, Parma, Italy
| | - Francesca Turroni
- Microbiome Research Hub, University of Parma, Parma, Italy
- Department of Chemistry, Life Sciences, and Environmental Sustainability, Laboratory of Probiogenomics, University of Parma, Parma, Italy
| | - Luca Carnevali
- Department of Chemistry, Life Sciences and Environmental Sustainability, Stress Physiology Lab, University of Parma, Parma, Italy.
- Microbiome Research Hub, University of Parma, Parma, Italy.
| | - Marco Ventura
- Microbiome Research Hub, University of Parma, Parma, Italy
- Department of Chemistry, Life Sciences, and Environmental Sustainability, Laboratory of Probiogenomics, University of Parma, Parma, Italy
| | - Andrea Sgoifo
- Department of Chemistry, Life Sciences and Environmental Sustainability, Stress Physiology Lab, University of Parma, Parma, Italy
- Microbiome Research Hub, University of Parma, Parma, Italy
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An J, Kim BS, Yoon HJ. Combination of gut microbiota, proinflammatory cytokine, and 18F-FDG PET as potential indicators for predicting breast cancer recurrence. Sci Rep 2025; 15:8313. [PMID: 40065046 PMCID: PMC11894217 DOI: 10.1038/s41598-025-92233-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 02/26/2025] [Indexed: 03/14/2025] Open
Abstract
Breast cancer occurs at a younger age compared to western countries in South Korea. Despite advancements in treatment methods such as targeted therapy and immunotherapy, the increasing number of patients underscores the importance of improving disease-free survival (DFS). In this study, we evaluated the associations between gut microbiota composition, inflammatory cytokine levels, and breast cancer recurrence in preoperative patients. Additionally, we developed a composite prognostic index by integrating these factors with PET/CT indices and clinical prognostic factors. This study showed that Prevotella abundance was significantly higher in the DFS group than in the recurrence group, and higher Prevotella abundance was associated with lower levels of the inflammatory cytokine IL-1β. Survival analysis revealed that patients with low Prevotella abundance and high IL-1β levels had a higher risk of breast cancer recurrence. PET markers, such as SUVtumor, SUVVAT, and SUVspleen, were also found to be significant prognostic indicators, with lower values associated with better survival outcomes. An integrated predictive model combining gut microbiota composition, cytokine levels, PET indices, and clinical factors demonstrated superior accuracy (AUC: 0.9025) in predicting breast cancer recurrence compared to individual components.
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Affiliation(s)
- Jeongshin An
- Institute of Convergence Medicine Research, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, 1071 Anyangcheon‑ro, Yangcheon‑gu, Seoul, 07985, Republic of Korea
- Department of Surgery, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, 1071 Anyangcheon‑ro, Yangcheon‑gu, Seoul, 07985, Republic of Korea
| | - Bom Sahn Kim
- Department of Nuclear Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, 260 Gonghang-daero, Gangseo-gu, Seoul, 07804, Republic of Korea.
| | - Hai-Jeon Yoon
- Department of Nuclear Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, 1071 Anyangcheon‑ro, Yangcheon‑gu, Seoul, 07985, Republic of Korea.
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Wang L, Hu R, Ma S, Yang X, Gong J, Xiang H, Shi M, Yuan X, Chen L, Zhang H, Tan B, He X, He J, Wu S. Dihydroquercetin attenuated Prevotella copri-caused intestinal injury by modulating gut microbiota and bile acids in weaned piglets. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2025; 20:303-310. [PMID: 39995524 PMCID: PMC11849659 DOI: 10.1016/j.aninu.2024.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 10/26/2024] [Accepted: 10/30/2024] [Indexed: 02/26/2025]
Abstract
Gut microbiota disruption during the weaning process is a significant factor of intestinal injury. Our previous studies have suggested that Prevotella may play a critical role in causing intestinal inflammation. This study aimed to clarify the impact of Prevotella copri on intestinal injury and the protecting effect by dihydroquercetin (DHQ) in weaned piglets. A total of 108 healthy Duroc × Landrace × Yorkshire weaned piglets, aged 21 d, were randomly allocated into 3 groups with 6 replicates and 6 piglets per replicate. The piglets were the following diets for 28 d: 1) a basal diet, 2) basal diet containing 1.0 × 108 CFU/kg P. copri, 3) basal diet supplemented with 1.0 × 108 CFU/kg P. copri and 100 mg/kg DHQ. Results showed that P. copri decreased significantly the average daily gain (ADG) (P < 0.001), which was recovered by supplementation of DHQ with decreased serum levels of malondialdehyde (MDA), interleukin (IL)-2 and IL-8 but increased total superoxide dismutase (T-SOD) activity and IL-10 in weaned piglets (P < 0.001). Moreover, DHQ increased the expression of tight junction proteins (claudin-2, occludin and tight junction protein zonula occludens protein-1 (ZO-1) and the mRNA expression of glutathione peroxidase 4 (GPX-4) in ileum (P < 0.001). Intestinal flora analysis showed that P. copri increased the relative abundance of Prevotella (P = 0.026) and Eubacterium coprostanoligenes group (P < 0.001), but decreased the relative abundance of Lachnospiraceae NK4A136 group (P < 0.001), while supplementation of DHQ reduced the relative abundance of Prevotella (P = 0.026). Metabolomics results indicated that P. copri enhanced the content of 12-OH bile acid, but decreased the contents of glycodeoxycholic acid (GDCA) and glycochenodeoxycholic acid (GCDCA) (P < 0.001), while DHQ reduced the 12-OH bile acid content (P < 0.001) and increased the GDCA content (P = 0.020). In summary, P. copri caused intestinal injury and reduced growth performance in weaned piglets, and DHQ showed a protective effect by modulating gut microbiota and bile acids metabolism.
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Affiliation(s)
- Long Wang
- Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Ruizhi Hu
- Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Siqi Ma
- Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Xizi Yang
- Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Jiatai Gong
- Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Hongkun Xiang
- Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Mingkun Shi
- Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Xupeng Yuan
- College of Animal Science and Technology, Hunan Biological and Electromechanical Polytechnic, Changsha 410127, China
| | - Liang Chen
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Hongfu Zhang
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Bie Tan
- Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Xi He
- Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Jianhua He
- Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Shusong Wu
- Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
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Sun J, Sun Y, Zou Y, Wang H, Rao B, Zhang X, Liu L, Zhang G, Cui G, Liu Q, Xing J, Xu N, Zheng C, Yu Z, Ren Z. Diagnostic Efficiency of Tongue-Coating Microbiome in Patients With SARS-CoV-2 Omicron Variant Infection and Recovery. INFECTIOUS MICROBES AND DISEASES 2025; 7:54-64. [DOI: 10.1097/im9.0000000000000175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/04/2025]
Abstract
Abstract
SARS-CoV-2 variants still pose threats to human public health. However, there has been little research regarding alterations in the tongue-coating microbiome in patients infected with the Omicron variant (PIOVs). Herein, we collected 963 tongue-coating samples prospectively, including 349 samples from PIOVs, 242 samples from recovered PIOVs, 300 samples from healthy controls (HCs) and 72 samples from patients infected with the original strain (PIOSs). We randomly selected tongue-coating samples from PIOVs and HCs as the discovery cohort and validation cohort. Tongue-coating microbiota was analyzed using Miseq sequencing. Our results showed that the tongue-coating microbial diversity of PIOVs was increased. We found that in PIOVs, the abundance was increased in 20 genera, including Prevonella and Atopobium, while the abundance was decreased in 23 genera, including Neisseria and Haemophilus. The classifier based on six optimal microbial markers had high diagnostic efficiency in the discovery cohort (area under the curve of 97.73%) and the validation cohort (area under the curve of 93.06%) between the PIOV and HC groups. Importantly, compared with PIOSs, PIOVs showed an increase in Fusobacterium. Recovery of patients was associated with the restoration of the tongue-coating microbiota. In conclusion, this study is the first to characterize the tongue-coating microbiota in PIOVs and to construct noninvasive diagnostic models, providing new strategies for the prevention and control of coronavirus variants.
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Affiliation(s)
- Junyi Sun
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ying Sun
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yawen Zou
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Haiyu Wang
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Benchen Rao
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xinyue Zhang
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Liwen Liu
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guizhen Zhang
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guangying Cui
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qi Liu
- Emergency Intensive Care Ward, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jiyuan Xing
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ning Xu
- Department of Stomatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chunfu Zheng
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zujiang Yu
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhigang Ren
- Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Du Z, Liu X, Xie Z, Wang Q, Lv Z, Li L, Wang H, Xue D, Zhang Y. The relationship between a high-fat diet, gut microbiome, and systemic chronic inflammation: insights from integrated multiomics analysis. Am J Clin Nutr 2025; 121:643-653. [PMID: 39746397 DOI: 10.1016/j.ajcnut.2024.12.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 10/29/2024] [Accepted: 12/26/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND The detrimental effects of a high-fat diet (HFD) extend beyond metabolic consequences and include systemic chronic inflammation (SCI), immune dysregulation, and gut health disruption. OBJECTIVES In this study, we used Mendelian randomization (MR) to investigate the relationship between HFD, gut microbiota, and SCI. METHODS Genetic variants associated with dietary fat were utilized to explore causal relationships. Genome-wide association study data for the analyses of the gut microbiota, inflammatory cytokines, immune cell characteristics, and serum metabolites were obtained from European individuals. Mediation analysis was used to reveal potential mediating factors. The GMrepo database was used to analyze the bacterial composition in different groups. Transcriptomic and single-cell sequencing analyses explored inflammation and barrier function in colonic tissue. RESULTS HFD consumption was linked to changes in the abundance of 3 bacterial families and 11 bacterial genera. Combined with the GMrepo database, the increased abundance of the genus Lachnospiraceae_FCS020group and the decreased abundance of genus Bacteroides and genus Barnesiella are consistent with the MR results. Transcriptomic and single-cell sequencing analyses revealed intestinal inflammation and mucosal barrier dysfunction in HFD-fed mice. MR revealed a link between HFD consumption and increased levels of interleukin (IL)-18 [odds ratio (OR): 3.64, 95%CI: 1.24, 10.69, P = 0.02], MIG (OR = 3.14, 95%CI: 1.17, 8.47, P = 0.02), IL-13 [OR = 3.21, 95% confidence interval (CI): 1.08, -9.52, P = 0.04], and IL-2RA (OR = 2.93, 95%CI: 1.01, 8.53, P = 0.049). Twenty-nine immune cell signatures, including altered monocyte and T-cell subsets, were affected by HFD consumption. Twenty-six serum metabolites that are linked to HFD consumption, particularly lipid and amino acid metabolites, were identified. The positive gut microbiota exhibit extensive associations with inflammatory cytokines. In particular, Lachnospiraceae_FCS020 group (OR: 1.93, 95% CI: 1.11, 3.37, P = 0.02) may play a mediating role in HFD-induced increases in IL-2RA concentrations. CONCLUSIONS Microbial dysbiosis appears to be an important mechanism for HFD-induced SCI. The Lachnospiraceae_FCS020 group may act as a key genus in HFD-mediated elevation of IL-2RA.
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Affiliation(s)
- Zhiwei Du
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xuxu Liu
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhihong Xie
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Qiang Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Shandong, China
| | - Zhenyi Lv
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lianghao Li
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Heming Wang
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dongbo Xue
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
| | - Yingmei Zhang
- Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
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Song X, Zhu X, Liu X, Wang Z, Kou Z, Liu W, Chen Y, Hu B, Ding X, Chen T, Yan T. Association of organophosphorus pesticides and glyphosate exposure with nasal flora and total IgE in solar greenhouse workers: A unique farmer group. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2025; 368:125698. [PMID: 39824336 DOI: 10.1016/j.envpol.2025.125698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 01/04/2025] [Accepted: 01/14/2025] [Indexed: 01/20/2025]
Abstract
Studies have shown that the presence of allergens, including insecticides, significantly increases the risk of occupational allergic diseases among solar greenhouse workers. However, no studies have investigated the relationship between organophosphorus pesticides (OPs) used by solar greenhouse workers and allergic diseases, and the role of nasal flora in this context remains unclear. Therefore, this study aimed to investigate the relationship between combined exposure to organophosphorus pesticides and glyphosate (GLY) with changes in total immunoglobulin E (IgE) levels, as well as to analyze the role of nasal flora in allergic status. We collected demographic data, urine, peripheral blood and nasal swab samples from 284 solar greenhouse workers. Six metabolites in urine were detected by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Total IgE concentration was determined by enzyme-linked immunosorbent assay (ELISA). Then, we evaluated the association between OPs and GLY with total IgE levels using logistic regression analysis. In addition, 66 participants received 16S rDNA sequencing of nasal flora, followed by community diversity and species difference analyses to identify distinct microbial communities between normal and elevated total IgE groups. A total of 284 participants were included in this study, of whom 132 (46.5%) and 152 (53.5%) were male and female, respectively. The median total IgE concentration in this population was 63.52 IU/mL, of which 89 (31.3%) belonged to the elevated total IgE group. Our results suggest that dimethylphosphorodithioate (DMDTP) was a risk factor for total IgE abnormality, and GLY was positively associated with total IgE abnormality. Additionally, 20 differential flora were identified between the elevated and normal IgE groups, of which at least seven were significantly associated with OPs, GLY and their metabolites. In conclusion, there was a positive correlation between exposure to OPs and GLY with total IgE abnormalities, as well as multiple nasal pathogenic flora.
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Affiliation(s)
- Xin Song
- Beijing Institute of Occupational Disease Prevention and Control, Beijing, 100093, China; Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, 100069, Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Xiaojun Zhu
- National Center for Occupational Safety and Health, National Health Commission of the People's Republic of China, Beijing, 102308, China.
| | - Xiaodong Liu
- Beijing Institute of Occupational Disease Prevention and Control, Beijing, 100093, China
| | - Zhihui Wang
- Beijing Institute of Occupational Disease Prevention and Control, Beijing, 100093, China
| | - Zhenxia Kou
- Gansu Provincial Center for Disease Control and Prevention, Lanzhou, 730000, China
| | - Wu Liu
- Jingyuan Country Center for Disease Control and Prevention, Baiyin, 730699, China
| | - Yonglan Chen
- Jingyuan Country Center for Disease Control and Prevention, Baiyin, 730699, China
| | - Binshuo Hu
- Beijing Institute of Occupational Disease Prevention and Control, Beijing, 100093, China
| | - Xiaowen Ding
- Beijing Institute of Occupational Disease Prevention and Control, Beijing, 100093, China
| | - Tian Chen
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, 100069, Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Tenglong Yan
- Beijing Institute of Occupational Disease Prevention and Control, Beijing, 100093, China.
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Chen J, Malhi KK, Li X, Xu X, Kang J, Zhao B, Xu Y, Li X, Li J. Metasilicate-based alkaline mineral water improves the growth performance of weaned piglets by maintaining gut-liver axis homeostasis through microbiota-mediated secondary bile acid pathway. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2025; 20:95-109. [PMID: 39949730 PMCID: PMC11821399 DOI: 10.1016/j.aninu.2024.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 08/31/2024] [Accepted: 09/19/2024] [Indexed: 02/16/2025]
Abstract
Weaning stress causes substantial economic loss in the swine industry. Moreover, weaning-induced intestinal barrier damage and dysfunction of the gut-liver axis are associated with reduced growth performance in piglets. Metasilicate-based alkaline mineral water (AMW) has shown potential therapeutic effects on gastrointestinal disorders; however, the mechanisms involved and their overall effects on the gut-liver axis have not been explored. Here, sodium metasilicate (SMS) was used to prepare metasilicate-based AMW (basal water + 500 mg/L SMS). A total of 240 newly weaned piglets were allocated to the Control and SMS groups (6 replicate pens per group and 20 piglets per pen) for a 15-day trial period. Histopathological evaluations were conducted using hematoxylin and eosin staining. To analyze the composition of the gut microbiota, 16S rRNA PacBio SMRT Gene Full-Length Sequencing was performed. Western blotting and immunofluorescence were employed to assess protein expression levels. Our results indicated that metasilicate-based AMW effectively alleviated weaning-induced colonic or liver morphological injury and inflammatory response, as well as liver cholesterol metabolism disorders. Further analysis showed that metasilicate-based AMW promoted deoxycholic acid (DCA) biosynthesis by increasing the abundance of Lactobacillus_delbrueckii in the colon (P < 0.001). This consequently improved weaning-induced colon and liver injury and dysfunction through the DCA-secondary bile acid (SBA) receptors (SBAR)-nuclear factor-kappaB (NF-κB)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) pathways. Growth performance parameters, including final body weight (P = 0.034) and average daily gain (P < 0.001), in the SMS group were significantly higher than those in the Control group. Therefore, metasilicate-based AMW maintains gut-liver axis homeostasis by regulating the microbiota-mediated SBA-SBAR pathway in piglets under weaning stress. Our research provides a new strategy for mitigating stress-induced gut-liver axis dysfunction in weaned piglets.
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Affiliation(s)
- Jian Chen
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 China
| | - Kanwar K. Malhi
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 China
| | - Xiaowei Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 China
| | - Xiangwen Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 China
| | - Jianxun Kang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 China
| | - Bichen Zhao
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 China
| | - Yaru Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 China
| | - Xuenan Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 China
- Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, China
| | - Jinlong Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 China
- Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, China
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Tangon N, Kumfu S, Chattipakorn N, Chattipakorn SC. Links between oropharyngeal microbiota and IgA nephropathy: A paradigm shift from isolated microbe to microbiome. Microbiol Res 2025; 292:128005. [PMID: 39675141 DOI: 10.1016/j.micres.2024.128005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/30/2024] [Accepted: 12/05/2024] [Indexed: 12/17/2024]
Abstract
Immunoglobulin A nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis globally, yet its pathogenesis remains incompletely understood. While much research has focused on the gut microbiome in the development of the disease, emerging evidence suggests that the oropharyngeal microbiota may also be a potential contributor. Studies have revealed significant alterations in oropharyngeal microbial diversity and specific bacterial taxa in IgAN patients, correlating with disease severity and progression. This review aims to comprehensively summarize and discuss the key findings from in vitro, in vivo, and clinical studies into the oropharyngeal bacteria and microbiome alterations in IgAN. Clinical studies have identified associations between certain oropharyngeal bacteria, particularly Cnm+Streptococcus mutans, Campylobacter rectus, and Porphyromonas gingivalis with IgAN patients and severe clinical outcomes with. In vitro and in vivo studies further establish a causal relationship between IgAN and oropharyngeal bacteria such as Streptococcus and Haemophilus. Microbiome analyses demonstrate dysbiotic patterns in IgAN patients and identify new potential bacterial genera that have yet to be explored experimentally but may potentially contribute to the disease's pathogenesis. Additionally, the use of these bacterial genera as diagnostic and prognostic biomarkers of IgAN has achieved promising performance. Overall, the evidence highlights the strong connection between oropharyngeal bacteria and IgAN through both causal and non-causal associations. Further investigation into these newly identified bacterial genera and integration of multi-omics data are necessary to uncover mechanisms, validate their role in IgAN, and potentially develop novel diagnostic and therapeutic approaches.
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Affiliation(s)
- Narongsak Tangon
- Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sirinart Kumfu
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nipon Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand; The Academy of Science, The Royal Society of Thailand, Bangkok, Thailand
| | - Siriporn C Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
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Wang X, Yue J, Guo S, Rahmatulla A, Li S, Liu Y, Chen Y. Dissolving microneedles: A transdermal drug delivery system for the treatment of rheumatoid arthritis. Int J Pharm 2025; 671:125206. [PMID: 39799999 DOI: 10.1016/j.ijpharm.2025.125206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 12/27/2024] [Accepted: 01/08/2025] [Indexed: 01/15/2025]
Abstract
Rheumatoid arthritis (RA) is an autoimmune disorder that impacts around 1% of the global population. Up to 20% of people become disabled within a year, which has a severely negative impact on their health and quality of life. RA has a complicated pathogenic mechanism, which initially affects small joints and progresses to larger ones over time. It can damage the skin, eyes, heart, kidney, and lung. Oral medications, intra-articular injections, and other treatments are being used; nevertheless, they have drawbacks, including low bioavailability, numerous adverse effects, and poor patient compliance. Dissolving microneedles (DMNs) are a safe and painless method for transdermal drug delivery, achieved through their ability to physically penetrate the epidermal barrier. They enable targeted drug delivery, significantly enhancing the bioavailability of medications and improving patient compliance. DMNs are particularly effective in delivering both lipophilic and high molecular weight biomolecules. The superior bioavailability of DMNs is demonstrated by the fact that low-dose DMN administration can achieve up to 25.8 times higher bioavailability compared to oral administration. This paper provides a comprehensive review of recent advancements in the use of DMNs for RA treatment, encompassing various materials (such as hyaluronic acid, chitosan, etc.), fabrication techniques (such as the two-step casting method, photopolymerization), and performance evaluations (including morphology, mechanical properties, skin penetration capability, solubility, and pharmacodynamics). Additionally, a thorough safety assessment has been conducted, revealing that DMNs cause minimal skin irritation and exhibit low cytotoxicity, ensuring their safety for clinical application. DMNs provide a highly effective and promising alternative to oral and injectable drug delivery systems, offering a novel therapeutic approach for RA patients that significantly improves treatment outcomes and enhances their quality of life.
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Affiliation(s)
- Xueni Wang
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine Tianjin China
| | - Jiang Yue
- Department of Endocrinology and Metabolism Renji Hospital School of Medicine Shanghai Jiaotong University Shanghai China
| | - Shijie Guo
- Shengzhou Silk Protein Biotechnology Application Research Institute Zhejiang China
| | - Aysha Rahmatulla
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine Tianjin China
| | - Shuangshuang Li
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine Tianjin China
| | - Yang Liu
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine Tianjin China.
| | - Yuzhou Chen
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine Tianjin China.
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Schwartz LT, Ladouceur JG, Russell MM, Xie SYL, Bu S, Kerver JM, Comstock SS. The Relationship Between Fiber Intake and Gut Bacterial Diversity and Composition During the Third Trimester of Pregnancy. Nutrients 2025; 17:773. [PMID: 40077643 PMCID: PMC11901921 DOI: 10.3390/nu17050773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 02/12/2025] [Accepted: 02/15/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND/OBJECTIVES High fiber (34-36 g/day) diets are recommended during pregnancy due to inverse associations with constipation and adverse pregnancy health outcomes, including pre-eclampsia and gestational diabetes. However, the mechanism for this protective effect is poorly defined. Fiber may be protective due to its impact on the composition and function of specific bacteria within the pregnancy gut microbiome. The purpose of this analysis was to investigate whether a sub-sample of cohort study participants in their third trimester met daily dietary fiber and vegetable intake recommendations and, in turn, how this impacted bacterial composition and butyrate-producing genes within the gut microbiome. METHODS Pregnant participants (n = 52) provided stool samples and survey data, which were used to calculate fiber and vegetable intake. Genomic DNA was extracted from the stool samples, followed by PCR to amplify the V4 region of the 16S rRNA gene. Amplicons were sequenced and mapped to the RDP reference. Quantitative real-time PCR was used to measure the abundance of bacterial genes for butyrate production. RESULTS Of the pregnant participants in this sample, 84.7% and 92.3% failed to meet recommendations in the Dietary Guidelines for Americans for dietary fiber and vegetable intake, respectively. All four participants who met the vegetable recommendation were a subset of those who met the fiber recommendation. The participants who met the pregnancy fiber recommendation had gut microbiotas with greater alpha diversity (Shannon and Inverse Simpson) than those who did not. However, there was no association between dietary fiber intake and the abundance of bacterial genes for butyrate production. CONCLUSIONS This research suggests that general fiber intake during pregnancy has a modest association with the gut bacterial community. These preliminary results demonstrate a need to improve fiber intake during pregnancy. Further, studies that measure the relationship between dietary intake of specific types of fiber and associations with specific gut bacterial community members and their functions are needed.
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Affiliation(s)
- Lindsay T. Schwartz
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA
| | - Jillian G. Ladouceur
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA
| | - Madeleine M. Russell
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA
| | - Shiyi Y. L. Xie
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA
| | - Sihan Bu
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA
| | - Jean M. Kerver
- Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48824, USA
| | - Sarah S. Comstock
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA
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Ferraioli M, Levani J, De Luca R, Matucci-Cerinic C, Gattorno M, Guiducci S, Bellando Randone S, Chimenti MS. What Is New and What Is Next for SAPHO Syndrome Management: A Narrative Review. J Clin Med 2025; 14:1366. [PMID: 40004896 PMCID: PMC11856149 DOI: 10.3390/jcm14041366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 02/11/2025] [Accepted: 02/14/2025] [Indexed: 02/27/2025] Open
Abstract
Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is a rare disease characterized by a sterile inflammatory osteitis and/or arthritis associated with a wide range of dermatological manifestations, such as acne, palmoplantar pustulosis, and psoriasis. This review, providing up-to-date knowledge on this disease, aims at informing researchers and clinicians to help them program future studies in order to improve patients' care. Due to the vast clinical heterogeneity that characterizes this disease, SAPHO syndrome has received various names; among these, chronic recurrent multifocal osteomyelitis represents the most used one. The various nomenclatures in use also reflect different approaches to its management. Indeed, considering the world-wide distribution and the vast onset age (from children to late adulthood), in addition to the multiform clinical presentation, its diagnosis and treatment are often challenging for clinicians. In this review, we provide valuable insights on SAPHO syndrome, delving into its many aspects: epidemiology, pathogenesis, clinical presentation, diagnosis, and classification. Most importantly, this paper addresses the continuously changing treatment panorama of this disease, from established drugs to newly introduced ones. Furthermore, a peculiar focus regards nonpharmacologic approaches, including traditional Chinese medicine, the apheresis technique, and surgery. Similarly, this review also discusses patients' lifestyle, including quality of life. To improve SAPHO syndrome's management, different knowledge gaps should be filled, such as its current epidemiology and pathogenesis. In turn, perfected knowledge in these fields could also advance research in therapy.
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Affiliation(s)
- Mario Ferraioli
- Rheumatology, Immunology and Clinical Allergology Unit, Department of Medicina dei Sistemi, University of Rome Tor Vergata, 00133 Rome, Italy;
| | - Juela Levani
- Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, AOU Careggi, 50121 Florence, Italy; (J.L.); (R.D.L.); (S.G.); (S.B.R.)
| | - Riccardo De Luca
- Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, AOU Careggi, 50121 Florence, Italy; (J.L.); (R.D.L.); (S.G.); (S.B.R.)
| | - Caterina Matucci-Cerinic
- Rheumatology and Autoinflammatory Diseases, IRCCS Istituto Giannina Gaslini; DINOGMI, University of Genoa, 16126 Genoa, Italy; (C.M.-C.); (M.G.)
| | - Marco Gattorno
- Rheumatology and Autoinflammatory Diseases, IRCCS Istituto Giannina Gaslini; DINOGMI, University of Genoa, 16126 Genoa, Italy; (C.M.-C.); (M.G.)
| | - Serena Guiducci
- Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, AOU Careggi, 50121 Florence, Italy; (J.L.); (R.D.L.); (S.G.); (S.B.R.)
| | - Silvia Bellando Randone
- Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, AOU Careggi, 50121 Florence, Italy; (J.L.); (R.D.L.); (S.G.); (S.B.R.)
| | - Maria Sole Chimenti
- Rheumatology, Immunology and Clinical Allergology Unit, Department of Medicina dei Sistemi, University of Rome Tor Vergata, 00133 Rome, Italy;
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Ali AY, Zahran SA, Eissa M, Kashef MT, Ali AE. Gut microbiota dysbiosis and associated immune response in systemic lupus erythematosus: impact of disease and treatment. Gut Pathog 2025; 17:10. [PMID: 39966979 PMCID: PMC11834511 DOI: 10.1186/s13099-025-00683-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 02/04/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND Gut microbial dysbiosis and leaky gut play a role in systemic lupus erythematosus (SLE). Geographical location and dietary habits affect the microbiome composition in diverse populations. This study explored the gut microbiome dysbiosis, leaky gut, and systemic immune response to gut bacterial consortium in patients with SLE exhibiting mild/moderate and severe disease activity. METHODS Fecal and blood samples were collected from patients with SLE and healthy volunteers. Genomic DNA was extracted from the stool samples and subjected to 16S rRNA amplicon sequencing and microbiome profiling. Additionally, enzyme-linked immunosorbent assays were employed to determine the serum lipopolysaccharide level, as an assessment of gut permeability, and the systemic immune response against gut bacteria. RESULTS Patients with SLE showed significantly lower gut bacterial richness and diversity, indicated by observed OTUs (56.6 vs. 74.44; p = 0.0289), Shannon (3.05 vs. 3.45; p = 0.017) and Simpson indices (0.91 vs. 0.94; p = 0.033). A lower Firmicutes-to-Bacteroidetes ratio (1.07 vs. 1.69; p = 0.01) was observed, with reduced genera such as Ruminococcus 2 (0.003 vs. 0.026; p = 0.0009) and Agathobacter (0.003 vs. 0.012; p < 0.0001) and elevated Escherichia-Shigella (0.04 vs. 0.006; p < 0.0001) and Bacteroides (0.206 vs. 0.094; p = 0.033). Disease severity was associated with a higher relative abundance of Prevotella (0.001 vs. 0.0001; p = 0.04). Medication effects included lower Romboutsia (0.0009 vs. 0.011; p = 0.005) with azathioprine and higher Prevotella (0.003 vs. 0.0002; p = 0.038) with cyclophosphamide. Furthermore, categorization by prednisolone dosage revealed significantly higher relative abundances of Slackia (0.0007 vs. 0.00002; p = 0.0088), Romboutsia (0.009 vs. 0.002; p = 0.0366), and Comamonas (0.002 vs. 0.00007; p = 0.0249) in patients receiving high-dose prednisolone (> 10 mg/day). No differences in serum lipopolysaccharide levels were found, but SLE patients exhibited elevated serum gut bacterial antibody levels, suggesting a systemic immune response. CONCLUSION This study confirms the gut microbiome dysbiosis in patients with SLE, influenced by disease severity and specific medication usage.
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Affiliation(s)
- Aya Y Ali
- Microbiology & Immunology Department, Faculty of Pharmacy, Future University in Egypt, Cairo, 12311, Egypt
| | - Sara A Zahran
- Microbiology & Immunology Department, Faculty of Pharmacy, Future University in Egypt, Cairo, 12311, Egypt.
| | - Mervat Eissa
- Rheumatology & Rehabilitation Department, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt
| | - Mona T Kashef
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
| | - Amal Emad Ali
- Microbiology & Immunology Department, Faculty of Pharmacy, Future University in Egypt, Cairo, 12311, Egypt
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Yang Y, Hu X, Yang L, Zhang H, Zheng H, Shen Z. Novel insights into seasonal airborne bacterial interactions and potential threats to human health in a northwest city, China. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2025; 367:125611. [PMID: 39756569 DOI: 10.1016/j.envpol.2024.125611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/24/2024] [Accepted: 12/29/2024] [Indexed: 01/07/2025]
Abstract
Bioaerosols significantly influence air quality and human health. This study investigated the diversity, structure, and interaction of bacterial communities in particulate matter (PM2.5) across four seasons in Xi'an. The results revealed that operational taxonomic units (OTUs) were the highest in autumn, reaching levels comparable to those in winter, but were 3.7 and 1.8 times higher than in summer and spring respectively. The Chao1 index was the highest in winter and the lowest in summer. Proteobacteria dominated in summer (38.8%) and spring (35.9%), while Actinobacteria was more abundant in autumn (43.1%) and winter (50.9%). Co-occurrence network analysis showed more complex microbial relationships in spring and summer, with increased bacterial competition observed in summer, evidenced by the highest negative edges ratio (8.7%). Potential pathogenic bacteria were most prevalent in winter (41.1%), compared to 12.1% in spring and 18.6% in summer. Notably, Rhodococcus and Gardnerella were significantly enriched in winter and autumn, while Acinetobacter and Bacteroides were more prevalent in spring and summer, as indicated by STAMP analysis. This study provides crucial insights into how seasonal changes affect bacterial interactions and the potential pathogenicity of airborne bacterial communities, highlighting their potential threats to human health.
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Affiliation(s)
- Yiming Yang
- Department of Environmental Science and Engineering, Xi'an Jiaotong University, Xi'an, 710049, China; Key Lab of Aerosol Chemistry & Physics, SKLLQG, Institute of Earth Environment, Chinese Academy of Sciences, Xi'an, 710049, China
| | - Xiaoyan Hu
- Department of Environmental Science and Engineering, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Liu Yang
- Department of Environmental Science and Engineering, Xi'an Jiaotong University, Xi'an, 710049, China; Key Lab of Aerosol Chemistry & Physics, SKLLQG, Institute of Earth Environment, Chinese Academy of Sciences, Xi'an, 710049, China.
| | - Hongai Zhang
- Department of Neonatology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 650 Xinsongjiang Rd, Songjiang District, Shanghai, 201620, China
| | - Honghao Zheng
- Key Lab of Aerosol Chemistry & Physics, SKLLQG, Institute of Earth Environment, Chinese Academy of Sciences, Xi'an, 710049, China
| | - Zhenxing Shen
- Department of Environmental Science and Engineering, Xi'an Jiaotong University, Xi'an, 710049, China.
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Liu K, Deng S, Zhou Y, Xu B, Zhang Y, Li W, Liu X, Yao X. Crosstalk Between the Skin Environment and Microbial Community in Immune-Related Skin Diseases. Clin Rev Allergy Immunol 2025; 68:16. [PMID: 39954089 DOI: 10.1007/s12016-025-09029-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/04/2025] [Indexed: 02/17/2025]
Abstract
The skin surface hosts diverse skin microbiota, including bacteria, fungi, and viruses. Intricate interactions between the skin microenvironment and microbial community are crucial for maintaining cutaneous homeostasis. This review explores the bidirectional relationship between the skin ecosystem and its microbiota. The skin microenvironment is shaped by a combination of intrinsic factors, dominated by sweat glands and pilosebaceous units, and external factors, such as UV radiation and personal care products, which create distinct niches that influence microbial colonization patterns across different skin regions. The skin microbiome, in turn, modulates the physical, chemical, immunological, and microbial barriers of the skin. We also discuss the alterations in this crosstalk in various immune-related skin conditions such as atopic dermatitis, psoriasis, rosacea, hidradenitis suppurativa, skin cancer, and aging. Understanding these interactions is vital for developing targeted microbiome-based therapies for various skin disorders. Further researches are needed to deepen insights into the microbial roles and their therapeutic potentials in skin health and disease.
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Affiliation(s)
- Kecheng Liu
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China
| | - Shuting Deng
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China
| | - Yuan Zhou
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China
| | - Beilei Xu
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China
| | - Yu Zhang
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China
| | - Wei Li
- Department of Dermatology, Institute of Dermatology, Huashan Hospital, Fudan University, Shanghai, Shanghai, 200040, China
| | - Xiaochun Liu
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China.
| | - Xu Yao
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China.
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Xing R, Du P, Wang Z, Fan Z, Wang L, Huang Y, Chen W, Si X. Porcine Bile Acids Improve Antioxidant Status and Immune Function by Increasing Hungatella Abundance with Different Protein Level Diets in Late-Laying Hens. Animals (Basel) 2025; 15:500. [PMID: 40002981 PMCID: PMC11851759 DOI: 10.3390/ani15040500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/08/2025] [Accepted: 01/13/2025] [Indexed: 02/27/2025] Open
Abstract
The modern livestock industry faces significant challenges due to the extension of production cycles and a growing shortage of feed resources. Low-protein (LP) diets offer potential environmental advantages whereas damage intestinal integrity and increase pro-inflammatory cytokines. Bile acids (BAs), metabolic products of cholesterol in the liver, possess strong antioxidative and immune properties. This study evaluated the effects of dietary porcine BA supplementation at different protein levels on the antioxidant status, immune function, and gut microbiota of late-laying hens. A 2 × 2 factorial design was employed with 198 Hy-Line Brown laying hens (62 weeks old), randomly divided into one of four treatment groups with 8 replicates for each treatment. Diets included normal (16.42%) or low-protein (15.35%) levels, with porcine BAs supplemented at 0 or 120 mg/kg (62-69 weeks) and 0 or 200 mg/kg (70-75 weeks) over 14 weeks. Dietary protein levels and bile acids had no effect on organ development in laying hens. Low-protein diets increased serum anti-inflammatory cytokines IL-4 and IL-10 but elevated pro-inflammatory cytokines IL-1β (p < 0.05), corroborated by higher IL-10 gene expression in the ileum mucosa (p < 0.05). The supplementation of bile acids improved immune function by increasing serum IL-4 and TGF-β while decreasing IL-6 levels (p < 0.05). Moreover, bile acids treatments upregulated IL-10, TGF-β and ZO-1 gene expression in the ileum mucosa (p < 0.05) and alleviated oxidative stress by enhancing serum GSH-Px activity (p < 0.05). Additionally, both low-protein diets and bile acids enriched beneficial cecal bacteria, including Hungatella and Blautia, primarily linked to immune function. These findings demonstrate that porcine bile acids administration improve antioxidant capacity, immune function and gut microbiota dysbiosis. These beneficial effects were associated with Hungatella and Blautia levels, which may be responsible for the porcine bile acids efficacy in poultry nutrition.
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Affiliation(s)
| | | | | | | | | | | | | | - Xuemeng Si
- Institute of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China; (R.X.); (P.D.); (Z.W.); (Z.F.); (L.W.); (Y.H.); (W.C.)
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Chiarenza A, Aluisio GV, Parrinello NL, Marino S, Corsale AM, Privitera GF, Azgomi M, La Spina E, Cambria D, Curtopelle A, Isola G, Botta C, Di Raimondo F, Romano A, Santagati M. BNT162b2 mRNA vaccination affects the gut microbiome composition of patients with follicular lymphoma and chronic lymphocytic leukemia. Biomark Res 2025; 13:25. [PMID: 39930533 PMCID: PMC11812150 DOI: 10.1186/s40364-025-00734-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 01/21/2025] [Indexed: 02/13/2025] Open
Abstract
BACKGROUND In both chronic lymphatic leukemia (CLL) and follicular lymphoma (FL) immunotherapy determines B-depletion that leads to temporary suppression of humoral immunity, which is clinically relevant especially during the COVID-19 pandemic, when most patients in the first wave received the BNT162b2 vaccine during anti-neoplastic treatment. METHODS To capture changes in the immunome and microbiome composition in CLL and FL patients upon mRNA-based vaccination, we designed a prospective, longitudinal study to profile both the humoral and the cellular response after exposure to the BNT162b2 COVID-19 vaccine. RESULTS In both CLL patients and FL patients, the second and third administrations of the BNT162b2 vaccine increased the titer of specific antibodies against SARS-CoV-2. In FL patients, vaccination induced expansion of central memory CD8 + CD57dim CD279 + T cells and reduction of the neutrophil subset myeloid 1 (CD14-CD15+CD16dimCD64+CD33-CD38+PDL1+HLA-DR-); in both cohorts, CD45RA + CD27 + CD279 + NK cells were expanded after a full cycle of vaccination. After vaccination, the genera Collinsella, Gemmiger, Lachnospiraceae, Blautia, Ruminococcus and Lactobacillus increased in both CLL patients and FL patients, whereas Faecalibacterium, Enterobacteriacae, and Enterococcus decreased. Multivariate analysis failed to identify factors associated with changes in microbiome communities among the CLL and FL cohorts, considering age, sex, exposure to anti-CD20 therapy and disease activity. Only in FL patients, alpha diversity was negatively correlated with neutrophil subsets myeloid 1 e 5 at baseline and positively correlated with neutrophil subset 6 after vaccination. PICRUSt2 analysis showed how microbiome can also affect the host health promoting chronic inflammation. The L-lysine biosynthesis pathway was more represented in CLL patients, whereas the L-valine degradation pathway and the anaerobic degradation of purine nucleobases were overrepresented in the FL cohort. CONCLUSIONS Taken together, our findings reveal the effect of the BNT162b2 vaccine in shaping the microbiome composition in CLL and FL patients, despite receiving treatment for their underlying active disease, and highlight the importance of a comprehensive analysis of the immunome and microbiome profiling to understand immune function in these cohorts of patients.
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Affiliation(s)
- Annalisa Chiarenza
- Divisione Di Ematologia, AOU Policlinico Rodolico San Marco, Catania, Italy
| | - Gaia Vertillo Aluisio
- Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section Microbiology University of Catania, Catania, Italy.
| | | | - Sara Marino
- Dipartimento Di Chirurgia E Specialità Medico Chirurgiche, Università Degli Studi Di Catania, Catania, Italy
| | - Anna Maria Corsale
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Grete Francesca Privitera
- Department of Clinical and Experimental Medicine, BioinformaticsUnit, University of Catania, Catania, Italy
| | - MojtabaShekarkar Azgomi
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Enrico La Spina
- Dipartimento Di Chirurgia E Specialità Medico Chirurgiche, Università Degli Studi Di Catania, Catania, Italy
| | - Daniela Cambria
- Dipartimento Di Chirurgia E Specialità Medico Chirurgiche, Università Degli Studi Di Catania, Catania, Italy
| | - Angelo Curtopelle
- Divisione Di Ematologia, AOU Policlinico Rodolico San Marco, Catania, Italy
| | - Gaetano Isola
- Dipartimento Di Chirurgia E Specialità Medico Chirurgiche, Università Degli Studi Di Catania, Catania, Italy
| | - Cirino Botta
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Francesco Di Raimondo
- Divisione Di Ematologia, AOU Policlinico Rodolico San Marco, Catania, Italy
- Dipartimento Di Chirurgia E Specialità Medico Chirurgiche, Università Degli Studi Di Catania, Catania, Italy
| | - Alessandra Romano
- Divisione Di Ematologia, AOU Policlinico Rodolico San Marco, Catania, Italy.
- Dipartimento Di Chirurgia E Specialità Medico Chirurgiche, Università Degli Studi Di Catania, Catania, Italy.
| | - Maria Santagati
- Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section Microbiology University of Catania, Catania, Italy.
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Cai X, Ren F, Yao Y. Gut microbiota and their metabolites in the immune response of rheumatoid arthritis: Therapeutic potential and future directions. Int Immunopharmacol 2025; 147:114034. [PMID: 39805176 DOI: 10.1016/j.intimp.2025.114034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 12/24/2024] [Accepted: 01/03/2025] [Indexed: 01/16/2025]
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation, damage, and loss of function. In recent years, the role of gut microbiota and its metabolites in immune regulation has attracted increasing attention. The gut microbiota influences the host immune system's homeostasis through various mechanisms, regulating the differentiation, function, and immune tolerance of immune cells. Dysbiosis of the gut microbiota in RA patients is closely associated with abnormal activation of immune cells and excessive secretion of inflammatory cytokines. Metabolites produced by the gut microbiota, such as short-chain fatty acids (SCFAs), tryptophan metabolites, bile acids, and amino acid metabolites, play a critical role in immune responses, regulating the functions of immune cells like T cells, B cells, and macrophages, and inhibiting the release of pro-inflammatory cytokines. Restoring the balance of the gut microbiota and optimizing the production of metabolic products may become a new strategy for RA treatment. This review discusses the role of gut microbiota and its metabolites in the immune response of RA, exploring how they influence the immunopathological process of RA through the regulation of immune cells and key immune factors. It also provides a theoretical basis for future therapeutic strategies based on gut microbiota modulation.
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Affiliation(s)
- Xiaoyu Cai
- Department of Pharmacy Hangzhou First People's Hospital Hangzhou China.
| | - Fujia Ren
- Department of Pharmacy Hangzhou Women's Hospital Hangzhou China
| | - Yao Yao
- Department of Pharmacy Women's Hospital School of Medicine Zhejiang University Hangzhou China
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Pinto S, Šajbenová D, Benincà E, Nooij S, Terveer EM, Keller JJ, van der Meulen–de Jong AE, Bogaards JA, Steyerberg EW. Dynamics of Gut Microbiota After Fecal Microbiota Transplantation in Ulcerative Colitis: Success Linked to Control of Prevotellaceae. J Crohns Colitis 2025; 19:jjae137. [PMID: 39225490 PMCID: PMC11836888 DOI: 10.1093/ecco-jcc/jjae137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 07/21/2024] [Accepted: 09/02/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is an experimental treatment for ulcerative colitis (UC). We aimed to study microbial families associated with FMT treatment success. METHODS We analyzed stools from 24 UC patients treated with 4 FMTs weekly after randomization for pretreatment during 3 weeks with budesonide (n = 12) or placebo (n = 12). Stool samples were collected 9 times pre-, during, and post-FMT. Clinical and endoscopic response was assessed 14 weeks after initiation of the study using the full Mayo score. Early withdrawal due to worsening of UC symptoms was classified as non-response. RESULTS Nine patients (38%) reached remission at week 14, and 15 patients had a partial response or non-response at or before week 14. With a Dirichlet multinomial mixture model, we identified 5 distinct clusters based on the microbiota composition of 180 longitudinally collected patient samples and 27 donor samples. A Prevotellaceae-dominant cluster was associated with poor response to FMT treatment. Conversely, the families Ruminococcaceae and Lachnospiraceae were associated with a successful clinical response. These associations were already visible at the start of the treatment for a subgroup of patients and were retained in repeated measures analyses of family-specific abundance over time. Responders were also characterized by a significantly lower Simpson dominance compared to non-responders. CONCLUSIONS The success of FMT treatment of UC patients appears to be associated with specific gut microbiota families, such as control of Prevotellaceae. Monitoring the dynamics of these microbial families could potentially be used to inform treatment success early during FMT. CLINICAL TRIAL REGISTRATION NUMBER The study was registered in the Netherlands Trial Register, with reference number NL9858.
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Affiliation(s)
- Susanne Pinto
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Dominika Šajbenová
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Elisa Benincà
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
| | - Sam Nooij
- Leiden University Center for Infectious Diseases (LUCID) Research, Leiden University Medical Center, Leiden, The Netherlands
| | - Elisabeth M Terveer
- Leiden University Center for Infectious Diseases (LUCID) Research, Leiden University Medical Center, Leiden, The Netherlands
- Netherlands Donor Feces Bank, LUCID Medical Microbiology & Infection Control, Leiden University Medical Center, Leiden, The Netherlands
| | - Josbert J Keller
- Netherlands Donor Feces Bank, LUCID Medical Microbiology & Infection Control, Leiden University Medical Center, Leiden, The Netherlands
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Gastroenterology, Haaglanden Medisch Centrum, The Hague, The Netherlands
| | | | - Johannes A Bogaards
- Department of Epidemiology and Data Science, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Amsterdam Institute for Infection and Immunity (AI&I), Amsterdam UMC, Amsterdam, The Netherlands
| | - Ewout W Steyerberg
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
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Ismail HM, Perera D, Mandal R, DiMeglio LA, Evans-Molina C, Hannon T, Petrosino J, Javornik Cregeen S, Schmidt NW. Gut Microbial Changes Associated With Obesity in Youth With Type 1 Diabetes. J Clin Endocrinol Metab 2025; 110:364-373. [PMID: 39078977 PMCID: PMC11747672 DOI: 10.1210/clinem/dgae529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 07/11/2024] [Accepted: 07/29/2024] [Indexed: 08/07/2024]
Abstract
CONTEXT Obesity is prevalent in type 1 diabetes (T1D) and is problematic with higher risk for diabetes complications. It is unknown to what extent gut microbiome changes are associated with obesity and T1D. OBJECTIVE This work aimed to describe the gut microbiome and microbial metabolite changes associated with obesity in T1D. We hypothesized statistically significant gut microbial and metabolite differences in lean T1D youth (body mass index [BMI]: 5%-<85%) vs those with obesity (BMI: ≥95%). METHODS We analyzed stool samples for gut microbial (using metagenomic shotgun sequencing) and short-chain fatty acid (SCFA) differences in lean (n = 27) and obese (n = 21) T1D youth in a pilot study. The mean ± SD age was 15.3 ± 2.2 years, glycated hemoglobin A1c 7.8 ± 1.3%, diabetes duration 5.1 ± 4.4 years, 42.0% female, and 94.0% were White. RESULTS Bacterial community composition showed between sample diversity differences (β-diversity) by BMI group (P = .013). There was a higher ratio of Prevotella to Bacteroides in the obese group (P = .0058). There was a differential distribution of significantly abundant taxa in either the lean or obese groups, including increased relative abundance of Prevotella copri, among other taxa in the obese group. Functional profiling showed an upregulation of branched-chain amino acid (BCAA) biosynthesis in the obese group and upregulation of BCAA degradation, tyrosine metabolism, and secondary bile acid biosynthesis in the lean group. Stool SCFAs were higher in the obese vs the lean group (P < .05 for all). CONCLUSION Our findings identify a gut microbiome and microbial metabolite signature associated with obesity in T1D. These findings could help identify gut microbiome-targeted therapies to manage obesity in T1D.
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Affiliation(s)
- Heba M Ismail
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Dimuthu Perera
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Rabindra Mandal
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Linda A DiMeglio
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Carmella Evans-Molina
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Tamara Hannon
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Joseph Petrosino
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Sara Javornik Cregeen
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Nathan W Schmidt
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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