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Xue J, Allaband C, Zuffa S, Poulsen O, Meadows J, Zhou D, Dorrestein PC, Knight R, Haddad GG. Gut microbiota and derived metabolites mediate obstructive sleep apnea induced atherosclerosis. Gut Microbes 2025; 17:2474142. [PMID: 40025767 PMCID: PMC11881840 DOI: 10.1080/19490976.2025.2474142] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 02/03/2025] [Accepted: 02/25/2025] [Indexed: 03/04/2025] Open
Abstract
Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia/hypercapnia (IHC), affects predominantly obese individuals, and increases atherosclerosis risk. Since we and others have implicated gut microbiota and metabolites in atherogenesis, we dissected their contributions to OSA-induced atherosclerosis. Atherosclerotic lesions were compared between conventionally-reared specific pathogen free (SPF) and germ-free (GF) Apoe-/- mice following a high fat high cholesterol diet (HFHC), with and without IHC conditions. The fecal microbiota and metabolome were profiled using 16S rRNA gene amplicon sequencing and untargeted tandem mass spectrometry (LC-MS/MS) respectively. Phenotypic data showed that HFHC significantly increased atherosclerosis as compared to regular chow (RC) in both aorta and pulmonary artery (PA) of SPF mice. IHC exacerbated lesions in addition to HFHC. Differential abundance analysis of gut microbiota identified an enrichment of Akkermansiaceae and a depletion of Muribaculaceae (formerly S24-7) family members in the HFHC-IHC group. LC-MS/MS showed a dysregulation of bile acid profiles with taurocholic acid, taurodeoxycholic acid, and 12-ketodeoxycholic acid enriched in the HFHC-IHC group, long-chain N-acyl amides, and phosphatidylcholines. Interestingly, GF Apoe-/- mice markedly reduced atherosclerotic formation relative to SPF Apoe-/- mice in the aorta under HFHC/IHC conditions. In contrast, microbial colonization did not show a significant impact on the atherosclerotic progression in PA. In summary, this research demonstrated that (1) IHC acts cooperatively with HFHC to induce atherosclerosis; (2) gut microbiota modulate atherogenesis, induced by HFHC/IHC, in the aorta not in PA; (3) different analytical methods suggest that a specific imbalance between Akkermansiaceae and Muribaculaceae bacterial families mediate OSA-induced atherosclerosis; and (4) derived bile acids, such as deoxycholic acid and lithocholic acid, regulate atherosclerosis in OSA. The knowledge obtained provides novel insights into the potential therapeutic approaches to prevent and treat OSA-induced atherosclerosis.
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MESH Headings
- Animals
- Gastrointestinal Microbiome/physiology
- Atherosclerosis/etiology
- Atherosclerosis/microbiology
- Atherosclerosis/metabolism
- Sleep Apnea, Obstructive/complications
- Sleep Apnea, Obstructive/microbiology
- Sleep Apnea, Obstructive/metabolism
- Mice
- Male
- Bacteria/classification
- Bacteria/genetics
- Bacteria/metabolism
- Bacteria/isolation & purification
- Diet, High-Fat/adverse effects
- Feces/microbiology
- Mice, Inbred C57BL
- RNA, Ribosomal, 16S/genetics
- Bile Acids and Salts/metabolism
- Metabolome
- Specific Pathogen-Free Organisms
- Disease Models, Animal
- Tandem Mass Spectrometry
- Mice, Knockout, ApoE
- Apolipoproteins E/genetics
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Affiliation(s)
- Jin Xue
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Celeste Allaband
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Simone Zuffa
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
- Collaborative Mass Spectrometry Innovation Center, University of California San Diego, San Diego, CA, USA
| | - Orit Poulsen
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Jason Meadows
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Dan Zhou
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Pieter C. Dorrestein
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
- Collaborative Mass Spectrometry Innovation Center, University of California San Diego, San Diego, CA, USA
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA
- Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA
| | - Gabriel G. Haddad
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Department of Neuroscience, University of California San Diego, La Jolla, CA, USA
- The Division of Respiratory Medicine, Rady Children’s Hospital, San Diego, CA, USA
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Castonguay-Paradis S, Demers-Potvin É, Rochefort G, Lacroix S, Perron J, Martin C, Flamand N, Raymond F, Di Marzo V, Veilleux A. Seasonal variations in circulating endocannabinoidome mediators and gut microbiota composition in humans. Gut Microbes 2025; 17:2476563. [PMID: 40111342 PMCID: PMC11926903 DOI: 10.1080/19490976.2025.2476563] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 01/20/2025] [Accepted: 03/03/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND The human gut microbiome-endocannabinoidome axis is crucial for several homeostatic processes, including inflammation and energy metabolism, and is influenced by many endogenous and exogenous factors, such as dietary habits. Changes in the gut microbiome in response to seasonal variations were previously reported and tentatively attributed to shifts in dietary patterns. However, there is a need for longitudinal studies in industrialized populations to comprehensively explore seasonal variations independently of lifestyle confounding factors. OBJECTIVE To investigate the longitudinal effects of seasonal variations on the composition of the gut microbiome and the circulating levels of endocannabinoidome mediators in humans, while elucidating the contributing factors underlying these changes. METHODS Plasma and fecal samples were collected at the end of both the winter and summer in a longitudinal cohort of 48 individuals living in Québec City (Canada). Dietary habits, medical history, fecal microbiota taxonomic composition and plasma levels of circulating N‑acyl‑ethanolamines (NAEs) and 2‑monoacyl-glycerols (2‑MAGs) were obtained at each time point. RESULTS Lower circulating levels of most NAEs were observed at the end of summer. These changes were accompanied by a reduction in the relative abundance of the Bifidobacteriaceae and Lachnospiraceae families, along with an increase in the abundance of the Bacteroidaceae and Ruminococcaceae families. These seasonal variations were not associated with concurrent changes in adiposity parameters, dietary intakes, physical activity habits, or vitamin D status. Importantly, the magnitude of the shift in gut microbiota composition from winter to summer was found to be associated with the seasonal variations in circulating endocannabinoidome (eCBome) mediators. CONCLUSION This study identified specific seasonal changes in gut microbiota composition and circulating levels of several NAEs, which were not associated with vitamin D status and lifestyle habits. It underscores the importance of the gut microbiota-endocannabinoidome axis in the pathophysiology of seasonal changes, and of considering seasons in clinical trials on these systems.
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Affiliation(s)
- Sophie Castonguay-Paradis
- Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Québec, QC, Canada
- École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation (FSAA), Université Laval, Québec, QC, Canada
- Canada Research Excellence Chair in the Microbiome-Endocannabinoidome mediators Axis in Metabolic Health (CERC-MEND), Université Laval ,Québec, Qc, Canada
| | - Élisabeth Demers-Potvin
- Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Québec, QC, Canada
- École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation (FSAA), Université Laval, Québec, QC, Canada
| | - Gabrielle Rochefort
- Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Québec, QC, Canada
- École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation (FSAA), Université Laval, Québec, QC, Canada
| | - Sébastien Lacroix
- Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Québec, QC, Canada
- Canada Research Excellence Chair in the Microbiome-Endocannabinoidome mediators Axis in Metabolic Health (CERC-MEND), Université Laval ,Québec, Qc, Canada
| | - Julie Perron
- Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Québec, QC, Canada
- École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation (FSAA), Université Laval, Québec, QC, Canada
| | - Cyril Martin
- Canada Research Excellence Chair in the Microbiome-Endocannabinoidome mediators Axis in Metabolic Health (CERC-MEND), Université Laval ,Québec, Qc, Canada
- Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ), Québec, QC, Canada
| | - Nicolas Flamand
- Canada Research Excellence Chair in the Microbiome-Endocannabinoidome mediators Axis in Metabolic Health (CERC-MEND), Université Laval ,Québec, Qc, Canada
- Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ), Québec, QC, Canada
- Département de médecine, Faculté de médecine, Université Laval, Québec, QC, Canada
| | - Frédéric Raymond
- Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Québec, QC, Canada
- École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation (FSAA), Université Laval, Québec, QC, Canada
- Canada Research Excellence Chair in the Microbiome-Endocannabinoidome mediators Axis in Metabolic Health (CERC-MEND), Université Laval ,Québec, Qc, Canada
| | - Vincenzo Di Marzo
- Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Québec, QC, Canada
- École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation (FSAA), Université Laval, Québec, QC, Canada
- Canada Research Excellence Chair in the Microbiome-Endocannabinoidome mediators Axis in Metabolic Health (CERC-MEND), Université Laval ,Québec, Qc, Canada
- Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ), Québec, QC, Canada
- Département de médecine, Faculté de médecine, Université Laval, Québec, QC, Canada
- Joint International Unit on Chemical and Biomolecular Research on the Microbiome and its Impact on Metabolic Health and Nutrition (UMI-MicroMeNu) between Université Laval and Consiglio Nazionale delle Ricerche, Institute of Biomolecular Chemistry, Italy
| | - Alain Veilleux
- Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Québec, QC, Canada
- École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation (FSAA), Université Laval, Québec, QC, Canada
- Canada Research Excellence Chair in the Microbiome-Endocannabinoidome mediators Axis in Metabolic Health (CERC-MEND), Université Laval ,Québec, Qc, Canada
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Deng S, Cao H, Li T, Wang X, Meng J, Zeng T, Zhang D, Zhang S, Wang G, Liu R, Zou T, Cai M, Lang R, Lu D, Gu J. Lachnospiraceae-bacterium alleviates ischemia-reperfusion injury in steatotic donor liver by inhibiting ferroptosis via the Foxo3-Alox15 signaling pathway. Gut Microbes 2025; 17:2460543. [PMID: 39882747 PMCID: PMC11784649 DOI: 10.1080/19490976.2025.2460543] [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: 11/13/2024] [Revised: 01/15/2025] [Accepted: 01/17/2025] [Indexed: 01/31/2025] Open
Abstract
Ischemia-reperfusion injury (IRI) is a major obstacle in liver transplantation, especially with steatotic donor livers. Dysbiosis of the gut microbiota has been implicated in modulating IRI, and Lachnospiraceae plays a pivotal role in regulating host inflammatory and immune responses, but its specific role in liver transplantation IRI remains unclear. This study explores whether Lachnospiraceae can mitigate IRI and its underlying mechanisms. We found Lachnospiraceae-bacterium (Lachn.) abundance was significantly reduced in rats with liver cirrhosis. Lachn.-treated rats exhibited improved intestinal permeability, reduced IRI severity in both normal and steatotic donor livers, and decreased levels of neutrophil and macrophage infiltration, and inflammatory cytokines. Multi-omics analysis revealed elevated pyruvate levels in transplanted livers after Lachn. treatment, alongside reduced Alox15 and Foxo3 expression. Mechanistically, Lachn.-derived pyruvate inhibited Alox15 expression and reduced ferroptosis in normal and steatotic donor livers. Furthermore, reduced nuclear translocation of Foxo3 further suppressed Alox15 expression, alleviating IRI, especially in steatotic donor livers. Clinical samples confirmed reduced donor livers IRI in cirrhotic recipients with high Lachn. abundance after liver transplantation. In conclusion, Lachn. alleviates IRI in steatotic donor liver transplantation by inhibiting ferroptosis via the Foxo3-Alox15 axis, providing a potential therapeutic strategy to modulate gut microbiota to alleviate IRI following liver transplantation.
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Affiliation(s)
- Shenghe Deng
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Huan Cao
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Tongxi Li
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xueling Wang
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Junpeng Meng
- Department of General Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Teng Zeng
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Di Zhang
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Shuhua Zhang
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Guoliang Wang
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ran Liu
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Tianhao Zou
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Mao Cai
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ren Lang
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China
| | - Di Lu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Jinyang Gu
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation
- Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei, China
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Steinert RE, Rehman A, Sadabad MS, Milanese A, Wittwer-Schegg J, Burton JP, Spooren A. Microbial micronutrient sharing, gut redox balance and keystone taxa as a basis for a new perspective to solutions targeting health from the gut. Gut Microbes 2025; 17:2477816. [PMID: 40090884 PMCID: PMC11913388 DOI: 10.1080/19490976.2025.2477816] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 02/05/2025] [Accepted: 03/05/2025] [Indexed: 03/18/2025] Open
Abstract
In health, the gut microbiome functions as a stable ecosystem maintaining overall balance and ensuring its own survival against environmental stressors through complex microbial interaction. This balance and protection from stressors is maintained through interactions both within the bacterial ecosystem as well as with its host. As a consequence, the gut microbiome plays a critical role in various physiological processes including maintaining the structure and function of the gut barrier, educating the gut immune system, and modulating the gut motor, digestive/absorptive, as well as neuroendocrine system all of which are crucial for human health and disease pathogenesis. Pre- and probiotics, widely available and clinically established, offer various health benefits primarily by beneficially modulating the gut microbiome. However, their clinical outcomes can vary significantly due to differences in host physiology, diets, individual microbiome compositions, and other environmental factors. This perspective paper highlights emerging scientific insights into the importance of microbial micronutrient sharing, gut redox balance, keystone species, and the gut barrier in maintaining a diverse and functional microbial ecosystem, and their relevance to human health. We propose a novel approach that targets microbial ecosystems and keystone taxa performance by supplying microbial micronutrients in the form of colon-delivered vitamins, and precision prebiotics [e.g. human milk oligosaccharides (HMOs) or synthetic glycans] as components of precisely tailored ingredient combinations to optimize human health. Such a strategy may effectively support and stabilize microbial ecosystems, providing a more robust and consistent approach across various individuals and environmental conditions, thus, overcoming the limitations of current single biotic solutions.
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Affiliation(s)
- Robert E. Steinert
- Health, Nutrition & Care (HNC), Dsm-Firmenich, Kaiseraugst, Switzerland
- Department of Surgery and Transplantation, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland
| | - Ateequr Rehman
- Health, Nutrition & Care (HNC), Dsm-Firmenich, Kaiseraugst, Switzerland
| | | | - Alessio Milanese
- Data Science, Science & Research, Dsm-Firmenich, Delft, Netherlands
| | | | - Jeremy P. Burton
- Department of Microbiology and Immunology, The University of Western Ontario, London, Canada
| | - Anneleen Spooren
- Health, Nutrition & Care (HNC), Dsm-Firmenich, Kaiseraugst, Switzerland
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Dai ZM, Xu ML, Zhang QQ, Zhu B, Wu JZ, Liu Q, Li Y, Li HB. Alterations of the gut commensal Akkermansia muciniphila in patients with COVID-19. Virulence 2025; 16:2505999. [PMID: 40360188 PMCID: PMC12091934 DOI: 10.1080/21505594.2025.2505999] [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: 02/22/2024] [Revised: 08/12/2024] [Accepted: 04/02/2025] [Indexed: 05/15/2025] Open
Abstract
Dysbiosis of gut microbiota is well established in coronavirus disease 2019 (COVID-19). While studies have attempted to establish a link between the gut commensal Akkermansia muciniphila (A. muciniphila) and COVID-19, the findings have been inconsistent and sometimes controversial. The intestinal microbial abundance information of COVID-19 patients was acquired and analysed from GMrepo database. Subsequently, A. muciniphila's metabolites, target-genes, and metabolite-target relationships was extracted from GutMGene database. Lastly, coronascape module in Metascape database is used for gene annotation and enrichment analysis in various host cells and tissues after SARS-CoV-2 infection. The results indicated that, in comparison to healthy people, A. muciniphila was significantly elevated in COVID-19 patients. This bacterium was found to be associated with heightened expression of IL-10, TLR2, TLR4, CLGN, CLDN4, TJP2, and TJP3, while concurrently experiencing a reduction in the expression of IL-12A and IL-12B in humans. The regulatory genes of A. muciniphila primarily enhance responses to viruses and cytokines, positively regulate cell migration, and control epithelial cell proliferation. Our study revealed a significant increase in the gut commensal A. muciniphila in COVID-19 patients. This bacterium can modulate host immune responses and may also serve as a probiotic with antiviral properties.
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Affiliation(s)
- Zhi-Ming Dai
- Department of Anesthesiology, The First People’s Hospital of Xianyang, Xianyang, China
| | - Meng-Lu Xu
- Department of Nephrology, The First Affiliated Hospital of Xi’an Medical University, Xi’an, China
| | - Qing-Qing Zhang
- Department of Anesthesiology, Ganzhou Hospital of Guangdong Provincial People’s Hospital, Ganzhou Municipal Hospital, Ganzhou, China
| | - Bo Zhu
- Department of Anesthesiology, The First People’s Hospital of Xianyang, Xianyang, China
| | - Jun-Zhe Wu
- Department of Physiology and Pathophysiology, Xi’an Jiaotong University School of Basic Medical Sciences, Xi’an, China
| | - Qi Liu
- Department of Physiology and Pathophysiology, Xi’an Jiaotong University School of Basic Medical Sciences, Xi’an, China
| | - Ying Li
- Department of Physiology and Pathophysiology, Xi’an Jiaotong University School of Basic Medical Sciences, Xi’an, China
| | - Hong-Bao Li
- Department of Physiology and Pathophysiology, Xi’an Jiaotong University School of Basic Medical Sciences, Xi’an, China
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Ding X, Chen Y, Du L, Li J, Meng X, Lv H, Tong B, Niu G, Jian T, Chen J. Benefits of inulin and fructo-oligosaccharides on high fat diet-induced type 2 diabetes mellitus by regulating the gut microbiota in mice. J Nutr Biochem 2025; 141:109908. [PMID: 40122150 DOI: 10.1016/j.jnutbio.2025.109908] [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: 08/08/2024] [Revised: 02/28/2025] [Accepted: 03/18/2025] [Indexed: 03/25/2025]
Abstract
Type 2 diabetes mellitus (T2DM) is pathologically associated with gut microbiota imbalance, which is implicated in disease progression through metabolic and inflammatory pathways. The therapeutic potential of inulin, a well-characterized prebiotic, has been explored to mitigate T2DM via microbiota modulation. However, the efficacy of this intervention, with its performance dependent on the degree of polymerization (DP), requires further investigation. This study assessed the therapeutic roles of inulin (DP3-60) and fructo-oligosaccharides (FOS, DP3-10) in T2DM management. Dietary administration of these prebiotic compounds demonstrated a significant capacity to alleviate multiple metabolic pathologies, including obesity, insulin resistance, systemic inflammation, oxidative stress, dyslipidemia and hepatic steatosis in high-fat diet (HFD)-fed induced T2DM mice. Significant superior efficacy was observed in FOS for ameliorating glucose metabolic dysregulation, adipocyte hypertrophy, liver weight, and histopathological alterations in colonic tissue, while inulin exhibited greater potency in alleviating oxidative stress. Both inulin and FOS enhanced gut microbiota diversity and richness in T2DM mice, accompanied by a significant reduction in Firmicutes/Bacteroidetes ratio. Notably, the S24-7 family emerged as a crucial microbial taxon modulated by both inulin and FOS. Furthermore, FOS demonstrated superior capacity to restore HFD-induced gut microbiota. Taxonomically significant amplicon sequence variants (ASVs), which were altered by HFD and modulated by inulin and FOS, exhibited distinct taxonomic profiles between the two compounds. This study provides preliminary evidence that the biological effects and beneficial properties of inulin-type fructans exhibit DP-dependent variations, which may enhance their efficient utilization in metabolic disorders.
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Affiliation(s)
- Xiaoqin Ding
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Yan Chen
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Lanlan Du
- Department of Food Science and Technology, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing 210037, China
| | - Jing Li
- Department of Food Science and Technology, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing 210037, China
| | - Xiuhua Meng
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Han Lv
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Bei Tong
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Guanting Niu
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Tunyu Jian
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
| | - Jian Chen
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China; Department of Food Science and Technology, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing 210037, China.
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7
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Silva EN, Dos Santos TCF, Teixeira VC, Belo TCA, Augusto LV, de Almeida LA, Corsetti PP. Amoxicillin-induced bacterial gut dysbiosis: A critical influence on mice reproduction and their offspring development. Microb Pathog 2025; 204:107594. [PMID: 40246155 DOI: 10.1016/j.micpath.2025.107594] [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: 01/07/2025] [Revised: 04/08/2025] [Accepted: 04/14/2025] [Indexed: 04/19/2025]
Abstract
The use of antibiotics such as amoxicillin can induce intestinal dysbiosis leading to rupture the essential microbiota role in regulating immune, metabolic, and reproductive functions. This study assessed the effects of amoxicillin-induced intestinal dysbiosis on the female mice reproductive function and its repercussions on their offspring. Female mice were treated with amoxicillin for 15 days (AMOX) showed an increase in Proteobacteria and a decrease in Firmicutes and Bacteroidetes in feces and estrous cycle changes, with a predominance of the metestrus and diestrus phases in the treated mice. During gestation the AMOX group presented reduced number of implantations and decreased embryonic viability, resulting in a higher rate of resorption. Differential gene expression of reproductive hormones in AMOX-treated female mice suggested that intestinal dysbiosis interferes with hormonal regulation during pregnancy. The survival, body development, and intestinal microbiota composition of offspring showed significantly altered patterns in the AMOX mice. These findings indicate that amoxicillin-induced intestinal dysbiosis affects not only the estrous cycle and reproductive hormones but also has lasting impacts on offspring development. The study highlights the need for caution in the use of antibiotics during pregnancy to avoid potential harm to maternal and offspring health.
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Affiliation(s)
- Evandro Neves Silva
- Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas (UNIFAL), Alfenas, 37130-001, Minas Gerais, Brazil; Professor Edson Antônio Velano University (UNIFENAS), Alfenas, 37132-440, Minas Gerais, Brazil
| | - Thaís Cristina Ferreira Dos Santos
- Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas (UNIFAL), Alfenas, 37130-001, Minas Gerais, Brazil; Professor Edson Antônio Velano University (UNIFENAS), Alfenas, 37132-440, Minas Gerais, Brazil; Laboratory National Biosciences, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, 13083-100, São Paulo, Brazil
| | - Vanessa Coelho Teixeira
- Professor Edson Antônio Velano University (UNIFENAS), Alfenas, 37132-440, Minas Gerais, Brazil
| | - Thiago Caetano Andrade Belo
- Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas (UNIFAL), Alfenas, 37130-001, Minas Gerais, Brazil
| | - Lara Vilela Augusto
- Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas (UNIFAL), Alfenas, 37130-001, Minas Gerais, Brazil
| | - Leonardo Augusto de Almeida
- Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas (UNIFAL), Alfenas, 37130-001, Minas Gerais, Brazil.
| | - Patrícia Paiva Corsetti
- Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas (UNIFAL), Alfenas, 37130-001, Minas Gerais, Brazil.
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8
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Bangolo A, Amoozgar B, Habibi M, Simms E, Nagesh VK, Wadhwani S, Wadhwani N, Auda A, Elias D, Mansour C, Abbott R, Jebara N, Zhang L, Gill S, Ahmed K, Ip A, Goy A, Cho C. Exploring the gut microbiome’s influence on cancer-associated anemia: Mechanisms, clinical challenges, and innovative therapies. World J Gastrointest Pharmacol Ther 2025; 16:105375. [DOI: 10.4292/wjgpt.v16.i2.105375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 03/19/2025] [Accepted: 03/20/2025] [Indexed: 06/03/2025] Open
Abstract
BACKGROUND Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies, which stems from the direct effects of malignancy, treatment-induced toxicities, and systemic inflammation. It affects patients’ survival, functional status, and quality of life profoundly. Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia. The gut microbiota, through its intricate interplay with iron metabolism, inflammatory pathways, and immune modulation, may either exacerbate or ameliorate anemia depending on its composition, and functional integrity. Dysbiosis, characterized by disruption in the gut microbial ecosystem, is very common in cancer patients. This microbial imbalance is implicated in anemia causation through diminished iron absorption, persistent low-grade inflammation, and suppression of erythropoiesis.
AIM To consolidate current evidence regarding the interplay between gut microbiome and anemia in the setting of malignancies. It aims to provide a detailed exploration of the mechanistic links between dysbiosis and anemia, identifies unique challenges associated with various cancer types, and evaluates the efficacy of microbiome-focused therapies. Through this integrative approach, the review seeks to establish a foundation for innovative clinical strategies aimed at mitigating anemia and improving patient outcomes in oncology.
METHODS A literature search was performed using multiple databases, including Google Scholar, PubMed, Scopus, and Web of Science, using a combination of keywords and Boolean operators to refine results. Keywords included “cancer-associated anemia”, “gut microbiome”, “intestinal microbiota”, “iron metabolism”, “gut dysbiosis”, “short-chain fatty acids”, “hematopoiesis”, “probiotics”, “prebiotics”, and “fecal microbiota transplantation”. Articles published in English between 2000 and December 2024 were included, with a focus on contemporary and relevant findings.
RESULTS Therapeutic strategies aimed at restoration of gut microbial homeostasis, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), can inhibit anemia-causing pathways by enhancing microbial diversity, suppressing detrimental flora, reducing systemic inflammation and optimizing nutrient absorption.
CONCLUSION Gut dysbiosis causes anemia and impairs response to chemotherapy in cancer patients. Microbiome-centered interventions, such as probiotics, prebiotics, dietary modifications, and FMT, have shown efficacy in restoring microbial balance, reducing inflammation, and enhancing nutrient bioavailability. Emerging approaches, including engineered probiotics and bacteriophage therapies, are promising precision-based, customizable solutions for various microbiome compositions and imbalances. Future research should focus on integrating microbiome-targeted strategies with established anemia therapies.
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Affiliation(s)
- Ayrton Bangolo
- Department of Hematology and Oncology, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Behzad Amoozgar
- Department of Hematology and Oncology, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Maryam Habibi
- Department of Research, Tulane National Primate Research Center, Covington, LA 70433, United States
| | - Elizabeth Simms
- Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States
| | - Vignesh K Nagesh
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Shruti Wadhwani
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Nikita Wadhwani
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Auda Auda
- Department of Family Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Daniel Elias
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Charlene Mansour
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Robert Abbott
- Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nisrene Jebara
- Columbia University School of Nursing, New York, NY 10032, United States
| | - Lili Zhang
- Department of Hematology and Oncology, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Sarvarinder Gill
- Department of Hematology and Oncology, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Kareem Ahmed
- Department of Medicine, University of Washington, Seattle, WA 98195, United States
| | - Andrew Ip
- Division of Lymphoma, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Andre Goy
- Division of Lymphoma, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Christina Cho
- Division of Stem Cell Transplant and Cellular Therapy, John Theurer Cancer Center, Hackensack, NJ 07601, United States
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9
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Yu RL, Weber HC. Irritable bowel syndrome, the gut microbiome, and diet. Curr Opin Endocrinol Diabetes Obes 2025; 32:102-107. [PMID: 39968682 DOI: 10.1097/med.0000000000000905] [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] [Indexed: 02/20/2025]
Abstract
PURPOSE OF REVIEW To provide an update of recent studies exploring the role of the gut microbiota and diet in the pathogenesis and treatment of irritable bowel syndrome (IBS). RECENT FINDINGS The human gut microbiome has been recognized as an important, active source of signaling molecules that explain in part the disorder of the gut brain interaction (DGBI) in IBS. Subsequent changes in the metabolome such as the production of short-chain fatty acids (SCFA) and serotonin are associated with IBS symptoms. Dietary components are recognized as important triggers of IBS symptoms and a diet low in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) has been shown effective and safe, even when used long-term. Fecal microbiota transplantation (FMT) in IBS has not shown sustained and effective IBS symptom reduction in controlled clinical trials. SUMMARY This update elucidates recent developments in IBS as it relates to clinical trial results targeting dietary and gut microbiota interventions. The gut microbiome is metabolically active and affects the bi-directional signaling of the gut-brain axis.
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Affiliation(s)
- Rosa Lu Yu
- Boston University Chobanian & Avedisian School of Medicine
| | - H Christian Weber
- Boston University Chobanian & Avedisian School of Medicine
- VA Boston Healthcare System, Section of Gastroenterology and Hepatology, Boston, Massachusetts, USA
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10
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Okunlola FO, Okunlola AR, Adetuyi BO, Soliman MES, Alexiou A, Papadakis M, Fawzy MN, El-Saber Batiha G. Beyond the gut: Unraveling the multifaceted influence of microbiome on cardiovascular health. Clin Nutr ESPEN 2025; 67:71-89. [PMID: 40064239 DOI: 10.1016/j.clnesp.2025.03.002] [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: 10/09/2024] [Revised: 03/02/2025] [Accepted: 03/04/2025] [Indexed: 03/15/2025]
Abstract
Cardiovascular disease is one of the leading causes of death worldwide. Even while receiving adequate pharmacological treatment for their hypertension, people are nonetheless at greater risk for cardiovascular disease. There is growing evidence that the gut microbiota may have major positive and negative effects on blood pressure and illnesses related with it as more study into this topic is conducted. Trimethylamine n-oxide (TMAO) and short-chain fatty acids (SCFA) are two major by-products of the gut microbiota. TMAO is involved in the formation of other coronary artery diseases, including atherosclerosis and hypertension, while SCFAs play an important role in controlling blood pressure. Numerous investigations have confirmed the established link between dietary salt intake and hypertension. Reducing sodium in the diet is linked to lower rates of cardiovascular disease morbidity and mortality as well as lower rates of blood pressure and hypertension. In both human and animal research, high salt diets increase local and systemic tissue inflammation and compromise gut architecture. Given that the gut microbiota constantly interacts with the immune system and is required for the correct maturation of immune cells, it is scientifically conceivable that it mediates the inflammatory response. This review highlights the therapeutic possibilities for focusing on intestinal microbiomes as well as the potential functions of the gut microbiota and its metabolites in the development of hypertension.
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Affiliation(s)
- Felix Oladele Okunlola
- Department of Natural Sciences (Biochemistry Option), Faculty of Pure and Applied Sciences, Precious Cornerstone University, Ibadan, Nigeria.
| | - Abimbola Rafiat Okunlola
- Department of Natural Sciences (Biochemistry Option), Faculty of Pure and Applied Sciences, Precious Cornerstone University, Ibadan, Nigeria.
| | - Babatunde Oluwafemi Adetuyi
- Department of Natural Sciences (Biochemistry Option), Faculty of Pure and Applied Sciences, Precious Cornerstone University, Ibadan, Nigeria.
| | - Mahmoud E S Soliman
- Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa.
| | - Athanasios Alexiou
- University Centre for Research & Development, Chandigarh University, Chandigarh-Ludhiana Highway, Mohali, Punjab, India; Department of Research & Development, Funogen, Athens, 11741, Greece.
| | - Marios Papadakis
- University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283, Wuppertal, Germany.
| | - Mohamed N Fawzy
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University- Arish Branch, Arish, 45511, Egypt.
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, AlBeheira, 22511, Egypt.
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11
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Zhang L, Tuoliken H, Li J, Gao H. Diet, gut microbiota, and health: a review. Food Sci Biotechnol 2025; 34:2087-2099. [PMID: 40351733 PMCID: PMC12064509 DOI: 10.1007/s10068-024-01759-x] [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: 09/13/2024] [Revised: 10/19/2024] [Accepted: 11/13/2024] [Indexed: 05/14/2025] Open
Abstract
The relationship between diet and human physical and mental health is highly interconnected and has been significantly correlated with the occurrence of various diseases, including neurological disorders, cancer, and chronic inflammatory diseases. Moreover, diet has been demonstrated to play a pivotal role in governing gut microbiota composition, making it one of the most influential factors. The diet is crucial in connecting humans and their gut microorganisms. The nutrients ingested supply energy to the body and serve as substrates for the metabolic processes of the gut microorganisms. Consequently, the gut flora and their metabolites reciprocally impact the host's metabolism, thereby influencing the physiological state of the human body. Extensive investigations on human and mouse models have revealed that diet potentially underlies various effects on human health and disease. Graphical abstract
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Affiliation(s)
- Longxiang Zhang
- The Second Department of Gastroenterology, the First Affiliated Hospital of Xinjiang, Medical University, Urumqi, 830000 Xinjiang China
| | - Haishaer Tuoliken
- The Second Department of Gastroenterology, the First Affiliated Hospital of Xinjiang, Medical University, Urumqi, 830000 Xinjiang China
| | - Jian Li
- The Second Department of Gastroenterology, the First Affiliated Hospital of Xinjiang, Medical University, Urumqi, 830000 Xinjiang China
| | - Hongliang Gao
- The Second Department of Gastroenterology, the First Affiliated Hospital of Xinjiang, Medical University, Urumqi, 830000 Xinjiang China
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12
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Chen Y, Wu N, Yan X, Kang L, Ou G, Zhou Z, Xu C, Feng J, Shi T. Impact of gut microbiota on colorectal anastomotic healing (Review). Mol Clin Oncol 2025; 22:52. [PMID: 40297498 PMCID: PMC12035527 DOI: 10.3892/mco.2025.2847] [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: 12/20/2024] [Accepted: 03/27/2025] [Indexed: 04/30/2025] Open
Abstract
Intestinal anastomosis is a critical procedure in both emergency and elective surgeries to maintain intestinal continuity. However, the incidence of anastomotic leakage (AL) has recently increased, reaching up to 20%, imposing major clinical and economic burdens. Substantial perioperative alterations in the intestinal microbiota composition may contribute to AL, particularly due to disruptions in key microbial populations essential for intestinal health and healing. The intricate interplay between the intestinal microbiota and the host immune system, along with microbial changes before and during surgery, significantly influences anastomotic integrity. Notably, specific pathogens such as Enterococcus and Pseudomonas aeruginosa have been implicated in AL pathogenesis. Preventive strategies including dietary regulation, personalized intestinal preparation, microbiota restoration and enhanced recovery after surgery protocols, may mitigate AL risks. Future research should focus on elucidating the precise mechanisms linking intestinal microbiota alterations to anastomotic healing and developing targeted interventions to improve surgical outcomes.
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Affiliation(s)
- Yangyang Chen
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Nian Wu
- Clinical Medical College, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
| | - Xin Yan
- Anesthesia Operating Room, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Liping Kang
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Guoyong Ou
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Zhenlin Zhou
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Changbo Xu
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Jiayi Feng
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Tou Shi
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
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13
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He Q, Feng Y, Zhang Y, Lin M. Association between the dietary index for gut microbiota and female infertility: The mediation effects of lymphocyte count and red blood cell folate. J Reprod Immunol 2025; 169:104528. [PMID: 40203596 DOI: 10.1016/j.jri.2025.104528] [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: 02/13/2025] [Revised: 03/22/2025] [Accepted: 03/31/2025] [Indexed: 04/11/2025]
Abstract
Previous studies have revealed a the relationship between changes in the gut microbiota composition and female infertility. While the association between the dietary index for gut microbiota (DI-GM) and female infertility remains unstudied. The correlation was investigated with NHANES data from 2013 to 2018, with dietary recall data being used to calculate the DI-GM. Mediation analysis was performed to explore the role of lymphocyte count (LC) and red blood cell (RBC) folate in the DI-GM-induced risk of female infertility risk. Among the 1555 individuals included in our study, 311 were diagnosed with female infertility. According to the weighted binary logistic regression analyses, when all the covariates were adjusted, a negative association was observed between the DI-GM score and the risk of female infertility (OR: 0.80, 95 %CI: 0.74-0.88). After grouping participants by DI-GM score, compared with scores in the lowest quartile (Q1), the scores in Q3 and Q4 of DI-GM score were negatively associated with female infertility in crude and adjusted models, with ORs (95 %CI; P for trend) of 0.44 (0.27-0.70; <0.001); 0.43 (0.28-0.64; <0.001) and 0.43(0.26-0.71; <0.001); 0.41(0.27-0.60; <0.001). Additionally, restricted cubic splines logistic analysis uncovered a nonlinear association between the DI-GM score and the prevalence of female infertility. Mediation analysis indicated that LC and RBC folate mediated 4.64 % and 7.08 %, respectively of the association of the DI-GM scores with risk of female infertility. The nomogram exhibited good performance in this study (AUC 0.70, 95 % CI = 0.67-0.73). Our research revealed that the DI-GM score was negatively related to risk of female infertility. Mediation analyses demonstrated that LC and RBC folate levels significantly mediate the association between the DI-GM and the prevalence of female infertility.
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Affiliation(s)
- Qingwen He
- Department of Public Health, Affiliated Women's Hospital of Jiangnan University, Wuxi, Jiangsu 214002, China
| | - Yangkun Feng
- Center of Reproductive Medicine, Affiliated Women's Hospital of Jiangnan University, Wuxi, Jiangsu 214002, China
| | - Yun Zhang
- Center of Reproductive Medicine, Affiliated Women's Hospital of Jiangnan University, Wuxi, Jiangsu 214002, China
| | - Mengyuan Lin
- Center of Reproductive Medicine, Affiliated Women's Hospital of Jiangnan University, Wuxi, Jiangsu 214002, China.
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14
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te Velde AA. Incorporating Real-World Variability in Clinical IBD Research. J Eval Clin Pract 2025; 31:e70117. [PMID: 40329440 PMCID: PMC12056217 DOI: 10.1111/jep.70117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Accepted: 04/09/2025] [Indexed: 05/08/2025]
Affiliation(s)
- Anje A. te Velde
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC location AMCAmsterdam Gastroenterology Endocrinology Metabolism (AGEM)University of AmsterdamAmsterdamThe Netherlands
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15
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Gal-Mandelbaum N, Carasso S, Kedem A, Ziv T, Keshet-David R, Abboud R, Zaatry R, Gefen T, Geva-Zatorsky N. Dietary carbohydrates alter immune-modulatory functionalities and DNA inversions in Bacteroides thetaiotaomicron. Nat Commun 2025; 16:4938. [PMID: 40436824 PMCID: PMC12120099 DOI: 10.1038/s41467-025-60202-9] [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: 08/15/2024] [Accepted: 05/15/2025] [Indexed: 06/01/2025] Open
Abstract
The gut bacteria environment is highly dynamic. Environmental conditions were shown to affect microbial composition. Yet, their influences on bacterial functionality (e.g., immune-modulation activity) are mostly overlooked. Distinct strains of the same species, and even the same bacterial strain, may have different effects on the immune system depending on their growth environment. Therefore, studying the functionality of strains under different conditions is crucial. We analyzed functional alterations in the gut symbiont Bacteroides thetaiotaomicron (B. theta) under different dietary components consumption in humans, upon white sugar consumption in mice, and in response to 190 different carbon sources in vitro. Dietary alterations affected the orientation of phase variable regions in B. theta in humans, in vivo, and in vitro, and altered B. theta's proteome and immune-modulatory functionality. Studying the effects of dietary components on the immune-modulatory functionalities of key members of the gut microbiota will allow for personalized dietary recommendations.
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Grants
- The Technion Institute of Technology, “Keren haNasi,” Cathedra, the Rappaport Technion Integrated Cancer Center, the Alon Fellowship for Outstanding Young Researchers, the Israeli Science Foundation (3165/20), the D. Dan and Betty Kahn Foundation’s gift to the University of Michigan, the Weizmann Institute, the Technion–Israel Institute of Technology Collaboration for Research, the Seerave Foundation, CIFAR (grant FL-000969/FL-001245/FL-001381), and the European Union (ERC, ExtractABact, 101078712).
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Affiliation(s)
- Noa Gal-Mandelbaum
- Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine and Research Institute, Rappaport Technion Integrated Cancer Center (RTICC), Technion-Israel Institute of Technology, Haifa, Israel
| | - Shaqed Carasso
- Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine and Research Institute, Rappaport Technion Integrated Cancer Center (RTICC), Technion-Israel Institute of Technology, Haifa, Israel
| | - Alon Kedem
- Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine and Research Institute, Rappaport Technion Integrated Cancer Center (RTICC), Technion-Israel Institute of Technology, Haifa, Israel
| | - Tamar Ziv
- Smoler Proteomics Center, Lokey Interdisciplinary Center for Life Sciences & Engineering, Technion-Israel Institute of Technology, Haifa, Israel
| | - Roni Keshet-David
- Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine and Research Institute, Rappaport Technion Integrated Cancer Center (RTICC), Technion-Israel Institute of Technology, Haifa, Israel
| | - Roberto Abboud
- Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine and Research Institute, Rappaport Technion Integrated Cancer Center (RTICC), Technion-Israel Institute of Technology, Haifa, Israel
| | - Rawan Zaatry
- Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine and Research Institute, Rappaport Technion Integrated Cancer Center (RTICC), Technion-Israel Institute of Technology, Haifa, Israel
| | - Tal Gefen
- Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine and Research Institute, Rappaport Technion Integrated Cancer Center (RTICC), Technion-Israel Institute of Technology, Haifa, Israel
| | - Naama Geva-Zatorsky
- Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine and Research Institute, Rappaport Technion Integrated Cancer Center (RTICC), Technion-Israel Institute of Technology, Haifa, Israel.
- CIFAR Humans & the Microbiome program, CIFAR, Toronto, Canada.
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16
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Chen W, Li ML, Zeng G, Xu XY, Yin SH, Xu C, Li L, Wen K, Yu XH, Wang G. Gut microbiota-derived metabolite phenylacetylglutamine in cardiovascular and metabolic disease. Pharmacol Res 2025:107794. [PMID: 40409519 DOI: 10.1016/j.phrs.2025.107794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Revised: 05/18/2025] [Accepted: 05/20/2025] [Indexed: 05/25/2025]
Abstract
The aging of population coupled with unhealthy dietary habits among residents has led to a rise in the incidence of cardiovascular and metabolic diseases (CVMDs). Extensive research has highlighted the role of gut microbiota-derived metabolites in CVMDs. Among these metabolites, phenylacetylglutamine (PAGln), a meta-organismal prothrombotic metabolite, has been proved to promote the progression of CVMDs. This bacterial derived metabolite is a byproduct of amino acid comes from phenylalanine (Phe) in the diet. There are increasing evidence showing that the level of PAGln is associated with the risk of developing CVMDs. To provide a comprehensive understanding of the role of PAGln in CVMDs, this review delves into the production and metabolic pathways of PAGln and discusses the links of PAGln and the pathogenesis of CVMDs.
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Affiliation(s)
- Wan Chen
- The First Affiliated Hospital, Department of Cardiology, Hengyang Medical school, University of South China, Hengyang, Hunan 421001, China; Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China
| | - Mei-Ling Li
- The First Affiliated Hospital, Department of Cardiology, Hengyang Medical school, University of South China, Hengyang, Hunan 421001, China
| | - Guang Zeng
- The First Affiliated Hospital, Department of Cardiology, Hengyang Medical school, University of South China, Hengyang, Hunan 421001, China
| | - Xiang-Yu Xu
- The First Affiliated Hospital, Department of Cardiology, Hengyang Medical school, University of South China, Hengyang, Hunan 421001, China
| | - Shan-Hui Yin
- The First Affiliated Hospital, Department of Cardiology, Hengyang Medical school, University of South China, Hengyang, Hunan 421001, China
| | - Can Xu
- The First Affiliated Hospital, Department of Cardiology, Hengyang Medical school, University of South China, Hengyang, Hunan 421001, China
| | - Linlin Li
- Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China
| | - Kaikai Wen
- Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China.
| | - Xiao-Hua Yu
- Institute of Clinical Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570100, China.
| | - Gang Wang
- The First Affiliated Hospital, Department of Cardiology, Hengyang Medical school, University of South China, Hengyang, Hunan 421001, China.
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17
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Oliver PJ, Civitelli L, Hu MT. The gut-brain axis in early Parkinson's disease: from prodrome to prevention. J Neurol 2025; 272:413. [PMID: 40394204 DOI: 10.1007/s00415-025-13138-5] [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: 03/07/2025] [Revised: 04/28/2025] [Accepted: 04/30/2025] [Indexed: 05/22/2025]
Abstract
Parkinson's disease is the second most common neurodegenerative disorder and fastest growing neurological condition worldwide, yet its etiology and progression remain poorly understood. This disorder is characterized pathologically by the prion-like spread of misfolded neuronal alpha-synuclein proteins in specific brain regions leading to Lewy body formation, neurodegeneration, and progressive neurological impairment. It is unclear what triggers Parkinson's and where α-synuclein protein aggregation begins, although proposed induction sites include the olfactory bulb and dorsal motor nucleus of the vagus nerve. Within the last 20 years, there has been increasing evidence that Parkinson's could be triggered by early microbiome changes and α-synuclein accumulation in the gastrointestinal system. Gut microbiota dysbiosis that alters gastrointestinal motility, permeability, and inflammation could enable prion-like spread of α-synuclein from the gut-to-brain via the enteric nervous system. Individuals with isolated rapid eye movement sleep behavior disorder have a high likelihood of developing Parkinson's and might represent a prodromal 'gut-first' subtype of the condition. The gut-first model of Parkinson's offers novel gut-based therapeutic avenues, such as anti-, pre-, and pro-biotic preparations and fecal microbiota transplants. Crucially, gut-based interventions offer an avenue to treat Parkinson's at early prodromal stages with the aim of mitigating evolution to clinically recognizable Parkinson's disease characterized by motor impairment.
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Affiliation(s)
- Patrick James Oliver
- Clinical Medical School, University of Oxford, Oxford, UK
- Green Templeton College, University of Oxford, Oxford, UK
| | - Livia Civitelli
- Nuffield Department of Clinical Neurosciences, Oxford Parkinsons' Disease Center, University of Oxford, Oxford, UK
| | - Michele T Hu
- Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK.
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
- Department of Neurology, West Wing, Level 3, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.
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18
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Gao X, Yang C, Feng Z, Liu P, Liu Z. The signature of the small intestinal epithelial and immune cells in health and diseases. Chin Med J (Engl) 2025:00029330-990000000-01558. [PMID: 40394804 DOI: 10.1097/cm9.0000000000003615] [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: 12/05/2024] [Indexed: 05/22/2025] Open
Abstract
ABSTRACT The small intestine is essential for digestion, nutrient absorption, immune regulation, and microbial balance. Its epithelial lining, containing specialized cells like Paneth and tuft cells, is crucial for maintaining intestinal homeostasis. Paneth cells produce antimicrobial peptides and growth factors that support microbial regulation and intestinal stem cells, while tuft cells act as chemosensors, detecting environmental changes and modulating immune responses. Along with immune cells such as intraepithelial lymphocytes, innate lymphoid cells, T cells, and macrophages, they form a strong defense system that protects the epithelial barrier. Disruptions in this balance contribute to chronic inflammation, microbial dysbiosis, and compromised barrier function-key features of inflammatory bowel disease, celiac disease, and metabolic syndromes. Furthermore, dysfunctions in the small intestine and immune cells are linked to systemic diseases like obesity, diabetes, and autoimmune disorders. Recent research highlights promising therapeutic strategies, including modulation of epithelial and immune cell functions, probiotics, and gene editing to restore gut health and address systemic effects. This review emphasizes the pivotal roles of small intestinal epithelia and immune cells in maintaining intestinal homeostasis, their involvement in disease development, and emerging treatments for intestinal and systemic disorders.
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Affiliation(s)
- Xiang Gao
- Center for Inflammatory Bowel Disease Research, Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Cuiping Yang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
| | - Zhongsheng Feng
- Center for Inflammatory Bowel Disease Research, Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Ping Liu
- Department of Gastroenterology, Wuhu First People's Hospital, Wuhu, Anhui 241000, China
| | - Zhanju Liu
- Center for Inflammatory Bowel Disease Research, Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
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Ullah H. Gut-vitamin D interplay: key to mitigating immunosenescence and promoting healthy ageing. Immun Ageing 2025; 22:20. [PMID: 40390005 PMCID: PMC12087203 DOI: 10.1186/s12979-025-00514-y] [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: 12/29/2024] [Accepted: 04/26/2025] [Indexed: 05/21/2025]
Abstract
BACKGROUND Immunosenescence is the loss and change of immunological organs, as well as innate and adaptive immune dysfunction with ageing, which can lead to increased sensitivity to infections, age-related diseases, and cancer. Emerging evidence highlights the role of gut-vitamin D axis in the regulation of immune ageing, influencing chronic inflammation and systemic health. This review aims to explore the interplay between the gut microbiota and vitamin D in mitigating immunosenescence and preventing against chronic inflammation and age-related diseases. MAIN TEXT Gut microbiota dysbiosis and vitamin D insufficiency accelerate immunosenescence and risk of chronic diseases. Literature data reveal that vitamin D modulates gut microbiota diversity and composition, enhances immune resilience, and reduce systemic inflammation. Conversely, gut microbiota influences vitamin D metabolism to promote the synthesis of active vitamin D metabolites with implications for immune health. CONCLUSIONS These findings underscore the potential of targeting gut-vitamin D axis to modulate immune responses, delay the immune ageing, and mitigate age-related diseases. Further research is needed to integrate vitamin D supplementation and microbiome modulation into strategies aimed at promoting healthy ageing.
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Affiliation(s)
- Hammad Ullah
- School of Pharmacy, University of Management and Technology, Lahore, 54000, Pakistan.
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20
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Han J, Meng X, Kong H, Li X, Chen P, Zhang XA. Links between short-chain fatty acids and osteoarthritis from pathology to clinic via gut-joint axis. Stem Cell Res Ther 2025; 16:251. [PMID: 40390010 PMCID: PMC12090658 DOI: 10.1186/s13287-025-04386-3] [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: 02/17/2025] [Accepted: 05/09/2025] [Indexed: 05/21/2025] Open
Abstract
Short-chain fatty acids (SCFAs), the primary metabolites produced by the microbial fermentation of dietary fibers in the gut, have a key role in protecting gut health. Increasing evidence indicates SCFAs can exert effects on distant tissues and organs beyond the gut via blood circulation. Osteoarthritis (OA) is a chronic inflammatory joint disease that severely diminishes the physical function and quality of life. However, effective clinical treatments for OA remain elusive. Recent studies have shown that SCFAs can exert beneficial effects on damaged joints in OA. SCFAs can mitigate OA progression by preserving intestinal barrier function and maintaining the integrity of cartilage and subchondral bone, suggesting that they have substantial potential to be the adjunctive treatment strategy for OA. This review described the SCFAs in the human body and their cellular signaling mechanism, and summarized the multiple effects of SCFAs (especially butyrate, propionate, and acetate) on the prevention and treatment of OA by regulating the gut-joint axis, providing novel insights into their promising clinical applications.
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Affiliation(s)
- Juanjuan Han
- College of Exercise and Health, Shenyang Sport University, Shenyang, 110100, China
| | - Xin Meng
- College of Exercise and Health, Shenyang Sport University, Shenyang, 110100, China
| | - Hui Kong
- College of Exercise and Health, Shenyang Sport University, Shenyang, 110100, China
| | - Xinran Li
- College of Exercise and Health, Shenyang Sport University, Shenyang, 110100, China
| | - Peijie Chen
- School of Exercise and Health, Shanghai University of Sport, Shanghai, 200438, China
| | - Xin-An Zhang
- College of Exercise and Health, Shenyang Sport University, Shenyang, 110100, China.
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21
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Wang X, Hu X, Chen F. Effect of high hydrostatic pressure treatment on antioxidant bioaccessibility from tomato juice and its modulation of gut microbiota. Food Chem 2025; 488:144839. [PMID: 40413953 DOI: 10.1016/j.foodchem.2025.144839] [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: 01/13/2025] [Revised: 05/18/2025] [Accepted: 05/18/2025] [Indexed: 05/27/2025]
Abstract
High hydrostatic pressure (HHP) processing can positively impact food safety and quality. However, limited information is available regarding the effect of HHP treatment on the bioaccessibility of individual carotenoids and polyphenols from tomato juice in the small intestine and colon. HHP treatment (550 MPa, 10 min) significantly increased the cis-lycopene proportion in both the small intestine and colon and increased the bioaccessibility of total phenols in the colon. After 24 h of fermentation, the microbial community structure of the HHP-treated tomato juice was closer to that of fresh tomato juice. Additionally, the relative abundance of Enterobacterales, Enterobacteriaceae, and Escherichia_Shigella was lower in the HHP-treated tomato juice in the fermentation system than in the thermally-treated (110 °C, 8.6 s) juice. Based on a healthy gut micro-ecology, the findings of this study provides a rationale for the processing of nutritionally healthy HHP-processed juice.
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Affiliation(s)
- Xuehua Wang
- National R&D Center for Se-rich Agricultural Products Processing, Hubei Engineering Research Center for Deep Processing of Green Se-rich Agricultural Products, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, PR China; College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, China Agricultural University, Beijing 100083, China.
| | - Xiaosong Hu
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, China Agricultural University, Beijing 100083, China.
| | - Fang Chen
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, China Agricultural University, Beijing 100083, China.
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22
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Zou S, Yang X, Zhou L. Gut microbiota in epilepsy: How antibiotics induce dysbiosis and influence seizure susceptibility. Microbiol Res 2025; 298:128225. [PMID: 40398011 DOI: 10.1016/j.micres.2025.128225] [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: 01/03/2025] [Revised: 04/27/2025] [Accepted: 05/16/2025] [Indexed: 05/23/2025]
Abstract
Epilepsy, a widespread chronic neurological disorder, has recently come under scrutiny for its potential association with the intricate dynamics of gut microbiota. Numerous investigations into the microbiota-gut-brain axis have revealed a close relationship between gut microbiota and epilepsy, suggesting gut microbiota as a potential treatment strategy. In clinical practice, a longstanding correlation has been observed between some kinds of antibiotics and the potential to induce seizures. Consequently, we have conceived a hypothesis that antibiotics might impact seizure activity by modulating the gut microbiota and influencing the physiological processes within the microbiota-gut-brain axis. In this review, our primary objective is to present the existing evidence and theoretical foundations supporting the hypothesis that dysbiosis within the gut microbiota may play a significant role in the pathophysiology of epilepsy. Furthermore, we aim to summarize the possible mechanisms between microbiota-gut-brain axis and epilepsy, offering insights into the selection of appropriate antibiotics for long-term epilepsy management and enhancing therapeutic efficacy through modulation of the gut microbiota. Further research is necessary to fully elucidate the intricate relationship between gut microbiota ecosystem and epilepsy. Exploring these connections holds promise for advancing our understanding of epilepsy pathogenesis and improving patient treatment and care.
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Affiliation(s)
- Shangnan Zou
- Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Clinical Neuroscience Center, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
| | - Xiaofeng Yang
- Guangzhou Medical University, Guangzhou, Guangdong, China; Department of Basic Medicine, Guangzhou National Laboratory, Guangzhou, Guangdong, China.
| | - Liemin Zhou
- Clinical Neuroscience Center, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China; Department of Neurology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
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23
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Hua Z, Lv Y, Zhang H, Mao T, Xv R, Pan M, Hu Y, Liu S, Fang Y. Effect of Raspberry ( Rubus indeaus L.) Juice Fermented by Limosilactobacillus fermentum FUA033 on the Human Gut Microbiota Cultured In Vitro: A Multi-Omics Approach. Foods 2025; 14:1796. [PMID: 40428575 PMCID: PMC12111400 DOI: 10.3390/foods14101796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2025] [Revised: 05/09/2025] [Accepted: 05/15/2025] [Indexed: 05/29/2025] Open
Abstract
The gut microbiota plays important functions in human health and influences immune responses, metabolic processes, and several physiological activities. The modulation of the gut microbiota through dietary interventions has emerged as a promising approach, leading to significant interest in the development of functional foods that provide health benefits. In this context, our study investigated the effects of raspberry juice fermented by Limosilactobacillus fermentum FUA033 on the structure and metabolism of the gut microbiota. We performed 16S rRNA gene sequencing and nontargeted metabolomics analyses to evaluate changes in the microbial composition and metabolite profiles resulting from fermentation. Our findings revealed that fermented raspberry juice considerably increased the gut microbial diversity and promoted the abundance of beneficial genera. Fermentation substantially increased the production of short-chain fatty acids, such as acetate and butyrate, which increased from 30.09 ± 5.23 mmol/L to 43.07 ± 3.31 mmol/L, and from 7.72 ± 1.72 mmol/L to 15.01 ± 1.26 mmol/L, respectively. Metabolomic analyses also showed significant enhancements in amino acid metabolism pathways, particularly those involving tyrosine, arginine, and proline. These results highlight the potential of fermented raspberry juice as a functional food to improve gut health and metabolic functions.
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Affiliation(s)
- Ziyan Hua
- Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Ocean University, Lianyungang 222005, China; (Z.H.); (H.Z.); (T.M.)
- Jiangsu Key Laboratory of Marine Bioresources and Environment, School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang 222005, China;
- Jiangsu Key Laboratory of Marine Biotechnology, School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang 222005, China
| | - Yunfan Lv
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 210029, China;
| | - Han Zhang
- Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Ocean University, Lianyungang 222005, China; (Z.H.); (H.Z.); (T.M.)
| | - Tianyi Mao
- Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Ocean University, Lianyungang 222005, China; (Z.H.); (H.Z.); (T.M.)
| | - Ruyu Xv
- Jiangsu Key Laboratory of Marine Bioresources and Environment, School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang 222005, China;
- Jiangsu Key Laboratory of Marine Biotechnology, School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang 222005, China
| | - Mingxuan Pan
- Jiangsu Innovation Center of Marine Bioresources, Jiangsu Coast Development Investment Co., Ltd., Nanjing 210019, China; (M.P.); (Y.H.)
| | - Yadong Hu
- Jiangsu Innovation Center of Marine Bioresources, Jiangsu Coast Development Investment Co., Ltd., Nanjing 210019, China; (M.P.); (Y.H.)
| | - Shu Liu
- Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Ocean University, Lianyungang 222005, China; (Z.H.); (H.Z.); (T.M.)
- Jiangsu Key Laboratory of Marine Bioresources and Environment, School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang 222005, China;
- Jiangsu Key Laboratory of Marine Biotechnology, School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang 222005, China
| | - Yaowei Fang
- Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Ocean University, Lianyungang 222005, China; (Z.H.); (H.Z.); (T.M.)
- Jiangsu Key Laboratory of Marine Bioresources and Environment, School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang 222005, China;
- Jiangsu Key Laboratory of Marine Biotechnology, School of Food Science and Engineering, Jiangsu Ocean University, Lianyungang 222005, China
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Li K, Lyu H, Zhang L, Ma S, Wang K, Fu Y, Zhang Y, Zhang X, Liu Z. Association between dietary patterns and suicide ideation among depressed adults: Insights from NHANES 2007-2020. J Affect Disord 2025; 377:235-244. [PMID: 39988135 DOI: 10.1016/j.jad.2025.02.073] [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: 01/04/2025] [Revised: 02/17/2025] [Accepted: 02/19/2025] [Indexed: 02/25/2025]
Abstract
BACKGROUND Dietary patterns are strongly linked to the risk of major depressive disorder (MDD). However, research on the relationship between dietary patterns and MDD with suicidal ideation (MDD + SI) are limited. The Healthy Eating Index (HEI)-2015, Dietary Inflammatory Index (DII), Comprehensive Dietary Antioxidant Index (CDAI), Oxidative Balance Score (OBS), and Dietary Index for Gut Microbiota (DI-GM) are five validated tools for assessing dietary patterns based on inflammation, antioxidant capacity, and gut microbiota diversity. This study aims to investigate the association between these dietary indices and MDD + SI. METHODS A total of 23,621 participants from the 2007-2020 National Health and Nutrition Examination Survey were included in this study. MDD and SI were assessed using the PHQ-9. Weighted multivariable logistic regression, subgroup analyses, and restricted cubic spline (RCS) models were applied to analyze the relationships between five dietary indices and the risks of MDD and MDD + SI. RESULTS All five dietary indices showed associations with MDD to varying degrees; however, only DI-GM exhibited a significant negative association with MDD + SI after adjustment for confounding factors. Subgroup and stratified linear trend analyses revealed that this association was stronger among former smokers, obese individuals and those with hypertension or diabetes. RCS analysis showed a significant non-linear relationship between DI-GM and MDD, while a significant linear dose-response relationship was observed for DI-GM and MDD + SI. LIMITATIONS Cross-sectional study designs cannot establish causality. CONCLUSION The findings of this study revealed a significant association between DI-GM and MDD + SI. Dietary interventions that promote gut microbiota diversity may help reduce the risk of MDD + SI.
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Affiliation(s)
- Kun Li
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Clinical Laboratory, Affiliated Hospital of West Anhui Health Vocational College, Lu'an, Anhui, China
| | - Honggang Lyu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Lihong Zhang
- Clinical Laboratory, Affiliated Hospital of West Anhui Health Vocational College, Lu'an, Anhui, China
| | - Simeng Ma
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Kun Wang
- Department of Psychiatry, Affiliated Hospital of West Anhui Health Vocational College, Lu'an, Anhui, China
| | - Ying Fu
- Department of Psychiatry, Affiliated Hospital of West Anhui Health Vocational College, Lu'an, Anhui, China
| | - Yalan Zhang
- Department of Psychiatry, Affiliated Hospital of West Anhui Health Vocational College, Lu'an, Anhui, China
| | - Xun Zhang
- Department of Psychiatry, Affiliated Hospital of West Anhui Health Vocational College, Lu'an, Anhui, China
| | - Zhongchun Liu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
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25
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Guo H, Bi Y, Zhang G, Luo S, Jia X, Yang R, Peng Y, Zhang L. Alcohol-induced bone loss driven by dysregulated spatial distribution of gut microbiota and PGD2-IL17 pathway-mediated osteoclast activation. Front Microbiol 2025; 16:1551028. [PMID: 40443995 PMCID: PMC12121995 DOI: 10.3389/fmicb.2025.1551028] [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: 01/03/2025] [Accepted: 03/25/2025] [Indexed: 06/02/2025] Open
Abstract
Introduction Alcohol-induced damage to bone microstructure leads to alcoholic osteoporosis (AOP). While prior studies have demonstrated alcohol's negative impact on bone density, the mechanisms by which alcohol induces osteoporosis through immune pathways, gut microbiota dysbiosis, and metabolic alterations remain insufficiently characterized. Given that alcohol is primarily absorbed in the upper gastrointestinal tract, in this research, we aimed to elucidate the role of spatial distribution disorders in gut microbiota and metabolites in the pathogenesis of alcohol-induced osteoporosis. We further sought to evaluate the potential of microbiota supplementation and targeted immunosuppressants as therapeutic strategies for related bone diseases. Methods An osteoporosis model using mice was established using alcohol drinking bottles, and bone loss was validated using micro-computed tomography. Segmented intestinal samples and fecal samples were analyzed using 16S rRNA sequencing and metabolomics. Mechanistic studies were conducted by supplementing R. intestinalis, prostaglandin D2 (PGD2), and its specific immune inhibitor, ramatroban. Analytical methods included tartrate-resistant acid phosphatase staining, flow cytometry, and enzyme-linked immunosorbent assay. Results Alcohol disrupted the spatial complexity of intestinal segments and fecal microbiota in mice, causing metabolic dysregulation and ultimately leading to elevated PGD2 levels. This, in turn, triggered Th17/Treg immune imbalance and osteoclast activation, resulting in bone loss. Supplementation with the probiotic R. intestinalis or inhibition of PGD2 significantly improved bone density and alleviate inflammation. Conclusion This study demonstrates that alcohol-induced elevation of PGD2 is a key pathogenic factor in AOP. PGD2 accelerates bone loss by promoting osteoclast formation through the activation of Th17 cells. Furthermore, this study highlights the importance of investigating the spatial distribution of gut microbiota and metabolites, providing potential targets and novel strategies for the precise treatment of AOP and other diseases associated with external stimuli.
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Affiliation(s)
- Haoyu Guo
- School of Medicine, Nankai University, Tianjin, China
- Department of Orthopedics, Chinese PLA General Hospital, Beijing, China
| | - Yujing Bi
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China
| | - Gongzi Zhang
- Department of Rehabilitation, Chinese PLA General Hospital, Beijing, China
| | - Shicheng Luo
- Department of Orthopedics, Chinese PLA General Hospital, Beijing, China
| | - Xiaopeng Jia
- Department of Orthopedics, Chinese PLA General Hospital, Beijing, China
- School of Medicine, Jinzhou Medical University, Jinzhou, China
| | - Ruifu Yang
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China
| | - Ye Peng
- Department of Orthopedics, Chinese PLA General Hospital, Beijing, China
| | - Lihai Zhang
- Department of Orthopedics, Chinese PLA General Hospital, Beijing, China
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Liu M, Han M, Fu Y, Zhang DD, Zhao YL, Li QY, Hu H, Guo HH, Huang LY, Tan CC, Xu W, Tan L. Associations between dietary index for gut microbiota and stroke, and the mediating role of inflammation: a prospective cohort study. Food Funct 2025. [PMID: 40357750 DOI: 10.1039/d5fo01041a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
Background: There has been a growing focus on the link between diet, gut microbiota, and stroke. The dietary index for gut microbiota (DI-GM), a novel indicator reflecting the effect of diet on gut microbiota diversity, has not been extensively studied in relation to stroke. This study aimed to examine the association between DI-GM and stroke, and to explore the potential mediating role of inflammatory biomarkers. Methods: We included 124 943 participants from the UK Biobank without stroke at baseline. The DI-GM was calculated using 24-hour dietary assessments. Cox proportional hazard models were employed to analyze the longitudinal associations of DI-GM with stroke and its subtypes. Restricted cubic spline (RCS) and subgroup analyses were also performed. Additionally, mediation analyses were conducted to explore the potential mediating role of inflammatory biomarkers between DI-GM and stroke risk. Results: During a median follow-up of 11.08 years, 3741 participants experienced a stroke, including 1626 ischemic strokes and 536 hemorrhagic strokes. After adjusting for covariates in the main model, higher DI-GM was significantly associated with reduced risks of stroke (HR = 0.97, 95% CI, 0.95-0.99, P < 0.001) and ischemic stroke (HR = 0.96, 95% CI, 0.94-0.99, P = 0.008), but not hemorrhagic stroke. No significant non-linear association was observed in the RCS analysis. Mediation analyses indicated that inflammatory biomarkers, including C-reactive protein, neutrophils, monocytes, leukocytes, neutrophil-to-lymphocyte ratio, and INFLA-score, partially mediated the association, accounting for 2.82% to 10.40% of the total effect. Conclusions: Higher DI-GM was associated with a reduced risk of stroke, particularly ischemic stroke. This protective association may be partially mediated by reductions in serum inflammatory biomarkers.
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Affiliation(s)
- Min Liu
- Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, China
| | - Meng Han
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
| | - Yan Fu
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
| | - Dan-Dan Zhang
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
| | - Yong-Li Zhao
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
| | - Qiong-Yao Li
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
| | - Hao Hu
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
| | - Hai-Hua Guo
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
| | - Liang-Yu Huang
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
| | - Chen-Chen Tan
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
| | - Wei Xu
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
| | - Lan Tan
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
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Pedersen LL, Sørum ME, Nissen A, Gerbek T, Kok K, Sørensen K, Fridh MK, Mølgaard C, Müller KG. Dietary Micronutrient Intake in Long-Term Survivors of Pediatric Hematopoietic Stem Cell Transplantation. Nutrients 2025; 17:1663. [PMID: 40431403 PMCID: PMC12113892 DOI: 10.3390/nu17101663] [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: 04/16/2025] [Revised: 05/06/2025] [Accepted: 05/07/2025] [Indexed: 05/29/2025] Open
Abstract
BACKGROUND Survivors of hematopoietic stem cell transplantation (HSCT) during childhood face significant late effects. This study aimed to map the dietary micronutrient intake of long-term survivors of pediatric HSCT and explore its associations with transplant outcomes, body composition, and physical capacity. METHODS We included 85 long-term survivors of HSCT (median age 30 years) The median time since HSCT was 19.9 years, reflecting a long-term survivor population. Dietary intake was assessed using a 3-day food record. Body composition was measured by DXA, and physical capacity was evaluated through cardiorespiratory fitness and physical performance tests. RESULTS We observed an inadequate intake of several vitamins and minerals including vitamins A, C, D, E, selenium, and potassium, with a median intake below recommendations. While dietary intake of vitamin D was reduced in patients with chronic graft versus host disease (cGvHD), the occurrence of cGvHD was not associated with overall micronutrient intake. Twelve percent of the participants had reduced skeletal muscle mass and 16% displayed a low bone mass density during DXA scans. These conditions were not related to the micronutrient intake. Likewise, reduced cardiorespiratory fitness and physical performance were unrelated to micronutrient intake. Total energy intake was found to significantly influence micronutrient intake (p = 0.001), explaining 66% of the variation. CONCLUSIONS Long-term survivors of pediatric HSCT demonstrated inadequate intake of multiple micronutrients. These findings suggest that inclusion of comprehensive micronutrient assessment and nutritional guidance should be considered for inclusion in follow-up care protocols.
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Affiliation(s)
- Louise Lindkvist Pedersen
- Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (L.L.P.); (M.E.S.); (K.K.); (K.S.); (M.K.F.)
- Pediatric Nutrition Unit, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark;
| | - Maria Ebbesen Sørum
- Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (L.L.P.); (M.E.S.); (K.K.); (K.S.); (M.K.F.)
| | - Anne Nissen
- Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (L.L.P.); (M.E.S.); (K.K.); (K.S.); (M.K.F.)
| | - Tina Gerbek
- Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (L.L.P.); (M.E.S.); (K.K.); (K.S.); (M.K.F.)
| | - Karin Kok
- Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (L.L.P.); (M.E.S.); (K.K.); (K.S.); (M.K.F.)
- Centre for Cancer and Organ Diseases, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
| | - Kaspar Sørensen
- Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (L.L.P.); (M.E.S.); (K.K.); (K.S.); (M.K.F.)
| | - Martin Kaj Fridh
- Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (L.L.P.); (M.E.S.); (K.K.); (K.S.); (M.K.F.)
| | - Christian Mølgaard
- Pediatric Nutrition Unit, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark;
- Department of Nutrition, Exercise and Sports, University of Copenhagen, 1172 Copenhagen, Denmark
| | - Klaus Gottlob Müller
- Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark; (L.L.P.); (M.E.S.); (K.K.); (K.S.); (M.K.F.)
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
- Institute for Inflammation Research, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
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Wang X. Unveiling the Gut Microbiota: How Dietary Habits Shape Health Through Microbiome Modulation. Nutrients 2025; 17:1650. [PMID: 40431390 PMCID: PMC12113806 DOI: 10.3390/nu17101650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2025] [Accepted: 04/30/2025] [Indexed: 05/29/2025] Open
Abstract
This Editorial provides an overview of the Special Issue "Dietary Habit, Gut Microbiome, and Human Health" which was recently published in Nutrients [...].
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Affiliation(s)
- Xi Wang
- Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
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Jiang L, Lau HCH, Zeng R, Yu J. Diet, Gastric Microbiota, and Metabolites in Gastric Tumorigenesis. RESEARCH (WASHINGTON, D.C.) 2025; 8:0693. [PMID: 40357361 PMCID: PMC12067930 DOI: 10.34133/research.0693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Revised: 04/09/2025] [Accepted: 04/15/2025] [Indexed: 05/15/2025]
Abstract
Gastric cancer (GC) is one of the most common cancers worldwide particularly in Asian populations, and certain diets have been associated with increased risk of GC. Recent advances in microbial profiling technology have facilitated investigations on microbes residing on the gastric mucosa and increasing evidence has revealed the critical roles of non-Helicobacter pylori gastric microbes in gastric tumorigenesis. On the other hand, diets can affect microbial communities, causing compositional and functional shift of the microbiota. In this review, we summarize the influence of various diets including processed meat, salt-preserved food, high-fat diet, and alcohol on the development and progression of GC. We also explore microbial metabolites and host-microbe interactions in gastric tumorigenesis, alongside dietary interventions targeting the microbiota for the prevention and management against GC.
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Affiliation(s)
- Lanping Jiang
- Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Harry Cheuk-Hay Lau
- Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Ruijie Zeng
- Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jun Yu
- Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
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Kang H, Huang D, Zhang W, Wang J, Liu Z, Wang Z, Jiang G, Gao A. Propionic acid/FBP1 is involved in polystyrene nanoplastic-induced cardiac injury via the gut-heart axis. Part Fibre Toxicol 2025; 22:10. [PMID: 40346689 PMCID: PMC12063461 DOI: 10.1186/s12989-025-00626-9] [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: 12/23/2024] [Accepted: 04/21/2025] [Indexed: 05/11/2025] Open
Abstract
BACKGROUND Micro-/nanoplastics (MNPLs) are widely found in the environment and have toxic effects on various organs and systems. However, the role of the gut-cardiac axis in cardiotoxicity induced by MNPLs has not yet been elucidated through research. RESULTS In this study, we examined the effects of 80 nm polystyrene nanoplastics (PS-NPs) on the heart and human cardiomyocytes (AC16) cells. Histopathological examination showed that NPs caused impaired cardiac function and increased myocardial collagen deposition. In view of the potential influence of gut microbiota and its metabolites on cardiac function, we conduct this study to investigate the specific effects they have on cardiac function. Analysis of cecal contents by 16 s ribosomal RNA (rRNA) and short chain fatty acids (SCFAs) revealed that colonic tissue damage, intestinal flora disorder, and reduction of propionic acid induced by PS-MPs were closely related to cardiac function. Further transcriptomic analysis of heart and colon tissues indicated that propionic acid may reduce cardiac function by reducing the expression of fructose-1, 6-biphosphatase 1 (FBP1). The hypothesis was further verified by in vitro intervention experiments with sodium propionate and FBP1 activator (BML-275). CONCLUSIONS In summary, our study systematically demonstrated the role of gut-heart axis in NPs-induced cardiac injury, and the specific process was that NPs exposure reduced propionate level, which in turn inhibited FBP1 expression to impair cardiac function. These findings provide new insights into NPs-induced cardiotoxicity and identifie potential therapeutic targets, providing clues for the prevention and treatment of NPs-induced cardiac injury in the future.
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Affiliation(s)
- Huiwen Kang
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, 10 Xitoutiao, You An Men, Beijing, 100069, China
| | - Danyang Huang
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, 10 Xitoutiao, You An Men, Beijing, 100069, China
| | - Wei Zhang
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, 10 Xitoutiao, You An Men, Beijing, 100069, China
| | - JingYu Wang
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, 10 Xitoutiao, You An Men, Beijing, 100069, China
| | - Ziyan Liu
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, 10 Xitoutiao, You An Men, Beijing, 100069, China
| | - Ziyan Wang
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, 10 Xitoutiao, You An Men, Beijing, 100069, China
| | - Guangyu Jiang
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, 10 Xitoutiao, You An Men, Beijing, 100069, China
| | - Ai Gao
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, 10 Xitoutiao, You An Men, Beijing, 100069, China.
- Beijing Key Laboratory of Environment and Aging, Capital Medical University, Beijing, 100069, China.
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Fang L, Peng H, Tan Z, Deng N, Peng X. The Role of Gut Microbiota on Intestinal Fibrosis in Inflammatory Bowel Disease and Traditional Chinese Medicine Intervention. J Inflamm Res 2025; 18:5951-5967. [PMID: 40357383 PMCID: PMC12067688 DOI: 10.2147/jir.s504827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 04/10/2025] [Indexed: 05/15/2025] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the intestine, frequently complicated by intestinal fibrosis. As fibrosis progresses, it can result in luminal stricture and compromised intestinal function, significantly diminishing patients' quality of life. Emerging evidence suggests that gut microbiota and their metabolites contribute to the pathogenesis of IBD-associated intestinal fibrosis by influencing inflammation and modulating immune responses. This review systematically explores the mechanistic link between gut microbiota and intestinal fibrosis in IBD and evaluates the therapeutic potential of traditional Chinese medicine (TCM) interventions. Relevant studies were retrieved from PubMed, Web of Science, Embase, Scopus, CNKI, Wanfang, and VIP databases. Findings indicate that TCM, including Chinese herbal prescriptions and bioactive constituents, can modulate gut microbiota composition and microbial metabolites, ultimately alleviating intestinal fibrosis through anti-inflammatory, immunemodulatory, and anti-fibrotic mechanisms. These insights highlight the potential of TCM as a promising strategy for targeting gut microbiota in the management of IBD-associated fibrosis.
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Affiliation(s)
- Leyao Fang
- The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China
- The Domestic First-Class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine, Changsha, People’s Republic of China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China
| | - Huiyi Peng
- The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China
- The Domestic First-Class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine, Changsha, People’s Republic of China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China
| | - Zhoujin Tan
- The Domestic First-Class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine, Changsha, People’s Republic of China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China
| | - Na Deng
- The Domestic First-Class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine, Changsha, People’s Republic of China
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China
| | - Xinxin Peng
- The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China
- The Domestic First-Class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine, Changsha, People’s Republic of China
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Zaiou M, Joubert O. Racial and Ethnic Disparities in NAFLD: Harnessing Epigenetic and Gut Microbiota Pathways for Targeted Therapeutic Approaches. Biomolecules 2025; 15:669. [PMID: 40427561 PMCID: PMC12109303 DOI: 10.3390/biom15050669] [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: 03/31/2025] [Revised: 04/28/2025] [Accepted: 04/29/2025] [Indexed: 05/29/2025] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern, impacting approximately 32.4% of the worldwide population. As a disease linked to metabolic dysfunction, NAFLD continues to rise alongside global increases in obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. There is considerable evidence indicating that NAFLD disproportionately affects racial, ethnic, and minority groups, although the exact reasons for these disparities remain elusive. Contributing factors to this disease may include socioeconomic status, cultural influences, stress, genetic factors, and lifestyle choices. Emerging evidence suggests that these causal factors could influence epigenetic mechanisms, particularly DNA methylation and histone modifications, as well as the composition and diversity of gut microbiota. Nevertheless, there is a scarcity of research that comprehensively examines the interplay between epigenetic changes and gut microbiome variations in relation to NAFLD disparities across different racial and ethnic populations globally. This paper intends to (i) explore the connections between NAFLD, ethnic disparities, gut microbiota composition, and epigenetic alterations, while reviewing pertinent studies that illustrate how these factors contribute to health inequities among various ethnic groups impacted by this disease; (ii) explore potential therapeutic targets and biomarkers to advance the management of NAFLD; and (iii) provide insights to enhance our understanding of the mechanisms associated with this disease, thereby promoting further research in this field. Advancements in this area are anticipated to enhance our understanding of disease susceptibilities in at-risk groups and to provide new therapeutic options for NAFLD and its associated complications.
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Affiliation(s)
- Mohamed Zaiou
- Université de Lorraine, CNRS, IJL, F-54000 Nancy, France;
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D’Urso F, Paladini F, Miraglia A, D’Amuri A, Chieppa M, Pollini M, Broccolo F. Translating Patent Innovation into Clinical Practice: Two Decades of Therapeutic Advancements in Dysbiosis Management. Microorganisms 2025; 13:1064. [PMID: 40431238 PMCID: PMC12114573 DOI: 10.3390/microorganisms13051064] [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: 02/10/2025] [Revised: 04/26/2025] [Accepted: 04/30/2025] [Indexed: 05/29/2025] Open
Abstract
Dysbiosis, characterized by a microbial imbalance, particularly within the gut microbiota, has emerged as a significant health concern linked to various diseases. This study analyzed 8097 patent documents from The Lens database (2005-2024) to examine global innovation trends in dysbiosis management. The patent filings showed exponential growth, peaking at 1222 documents in 2022, with the United States leading in publications (4361 documents). The analysis revealed three primary innovation clusters: bacterial-based therapeutics (44.8% of patents), specific therapeutic applications (27.6%), and diagnostic methods (15.9%). The disease associations predominantly included inflammatory conditions, infections, and cancer. The patent classifications highlighted a significant focus on probiotic development and microbiota modulation. The surge in patent activity since 2014 correlates with advances in DNA sequencing technology and the growing recognition of dysbiosis's role in human health. This analysis provides valuable insights into the evolving landscape of microbiome therapeutics and future directions for dysbiosis management.
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Affiliation(s)
- Fabiana D’Urso
- Department of Experimental Medicine (DiMeS), University of Salento, 73100 Lecce, Italy; (F.P.); (A.M.); (A.D.); (M.C.); (M.P.)
| | | | | | | | | | | | - Francesco Broccolo
- Department of Experimental Medicine (DiMeS), University of Salento, 73100 Lecce, Italy; (F.P.); (A.M.); (A.D.); (M.C.); (M.P.)
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Mei S, Chen Y, Long Y, Cen X, Zhao X, Zhang X, Ye J, Gao X, Zhu C. Association of gut microbiota with overweight/obesity combined with gestational diabetes mellitus. J Med Microbiol 2025; 74. [PMID: 40366751 DOI: 10.1099/jmm.0.002010] [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] [Indexed: 05/15/2025] Open
Abstract
Introduction. Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and negatively affects the health of mothers and infants. The aim of this study was to explore the associations between gut microbiota and the risk of GDM amongst overweight/obese women, and the interaction between gut microbiota dysbiosis and overweight/obesity in pregnant women with GDM.Hypothesis/Gap statement. Previous studies revealed that there may be a link between gut microbiota and GDM and obesity, but these studies have not reported the associations between gut microbiota and the risk of GDM amongst overweight/obese women, whilst the interaction between gut microbiota dysbiosis and overweight/obesity in pregnant women with GDM remains unknown.Aim. Based on a prospective cohort study, we explored the composition of gut microbiota in overweight/obese pregnant women and its association with GDM.Methodology.Participants (n=1820) were enrolled from the Pregnancy Metabolic Disease and Adverse Pregnancy Outcome cohort in Guangzhou, China, between 2019 and 2021. The participants' information and faecal samples were collected, and the relative abundance of faecal microbiota was profiled using 16S rRNA V4 region sequencing. Pregnant women were divided into four groups: non- overweight (NOW)/obese without GDM (OB- NGDM), overweight (OW)/OB- NGDM, NOW/obese with GDM (OB- GDM) and OW/OB- GDM. Linear discriminant analysis effect size (LEfSe) analysis, Spearman's correlation analysis and t- test were performed to estimate the association amongst microbiota, pre- pregnancy BMI and oral glucose tolerance test (OGTT) glucose levels.Results. Blautia, Anaerostipes, Synergistes (P<0.001) and Christensenellaceae_R_7_group (P=0.007) were significantly different between NOW/OB-GDM and OW/OB-GDM groups after adjusting for age. Odoribacter, Anaerostipes, Monoglobus, Romboutsia, Oscillospiraceae__UCG-003, Blautia and Dialisterwere significantly correlated with both OGTT 1 h (P<0.001) and 2 h (P<0.05) blood glucose levels, whilst Lactobacillus(P<0.001) were significantly correlated with OGTT 2 h blood glucose levels. Synergistes(P<0.001) were significantly correlated with OGTT fasting glucose levels, and Megasphaera and Odoribacter(P<0.05) were significantly correlated with pre-pregnancy BMI.Conclusions. GDM and OB/OW women was experiencing microbiota dysbiosis, especially the microbial communities related to glucose metabolism.
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Affiliation(s)
- Shanshan Mei
- Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, PR China
| | - Yisheng Chen
- Department of Epidemiology and Health Statistics, School of Public Health, Guangzhou Medical University, Guangzhou, 511436, PR China
| | - Yan Long
- Department of Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, PR China
| | - Xueqing Cen
- Department of Epidemiology and Health Statistics, School of Public Health, Guangzhou Medical University, Guangzhou, 511436, PR China
| | - Xueqin Zhao
- Department of Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, PR China
| | - Xiaoyan Zhang
- Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, PR China
| | - Jingyi Ye
- Department of Epidemiology and Health Statistics, School of Public Health, Guangzhou Medical University, Guangzhou, 511436, PR China
| | - Xiaoli Gao
- Faculty of Dentistry, National University of Singapore, Singapore, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | - Chunyan Zhu
- Department of Epidemiology and Health Statistics, School of Public Health, Guangzhou Medical University, Guangzhou, 511436, PR China
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Kocyigit E, Özturan Şirin A, Ozkan N. Associations Between Microbiota Awareness, Healthy Eating Attitude, and Sociodemographic Factors in University Students. Food Sci Nutr 2025; 13:e70280. [PMID: 40365038 PMCID: PMC12070035 DOI: 10.1002/fsn3.70280] [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: 02/25/2025] [Revised: 04/03/2025] [Accepted: 05/06/2025] [Indexed: 05/15/2025] Open
Abstract
The global epidemic of diet-related chronic diseases emphasizes the significance of the human gut microbiota in dietary physiological effects and the etiology of chronic diseases. This research aimed to assess the relationship between microbiota awareness, healthy eating attitudes, and sociodemographic factors in university students. Two hundred forty-two university students participated in this descriptive and analytical study in Aydın and Ordu, Türkiye. University students completed a general information form, anthropometric measures, the Attitude Scale for Healthy Nutrition, the Microbiota Awareness Scale, and a probiotic and prebiotic food frequency questionnaire. In total, 48 (19.8%) male and 194 (80.2%) female students participated in the study. Nutrition and dietetics students had higher total scores and sub-factor scores in ASHN and microbiota awareness and lower body mass index compared to other departments (p < 0.05). A positive and significant correlation was found between the Attitude Scale for Healthy Nutrition and Microbiota Awareness Scale total scores. Conversely, a negative statistically significant correlation was observed between body mass index and the total score of the Microbiota Awareness Scale (p < 0.05). The frequency of probiotic and prebiotic food consumption was higher in nutrition and dietetics students compared to other departments. A higher Attitude Scale for Healthy Nutrition, studying in the nutrition and dietetic department, knowing the term microbiota, and self-assessment on microbiota knowledge as good were associated with increased awareness of microbiota (p < 0.05). Given this positive association, integrating healthy nutrition, microbiota, probiotics, and prebiotics into the educational curricula for all university departments, scientific conferences, and academic research may enhance microbiota awareness among university students.
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Affiliation(s)
- Emine Kocyigit
- Department of Nutrition and DieteticsFaculty of Health Sciences, Ordu UniversityOrduTürkiye
| | - Ayçıl Özturan Şirin
- Department of Nutrition and DieteticsFaculty of Health Sciences, Aydın Menderes UniversityAydınTürkiye
| | - Nilüfer Ozkan
- Department of Nutrition and DieteticsFaculty of Health Sciences, Ordu UniversityOrduTürkiye
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Gu JM, Zhao M, Zhu J, Tao HW, Shao XP, Qin LQ, Ge YY, Chen GC. Dietary inflammatory potential, genetic predisposition, and incidence of Crohn's disease and ulcerative colitis. Nutr Metab (Lond) 2025; 22:35. [PMID: 40312362 PMCID: PMC12044715 DOI: 10.1186/s12986-025-00934-z] [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: 12/09/2024] [Accepted: 04/23/2025] [Indexed: 05/03/2025] Open
Abstract
BACKGROUND Evidence for a potential link between dietary inflammatory potential and inflammatory bowel disease is limited, and the moderating role of genetic susceptibility remains to be assessed. OBJECTIVE To evaluate energy-adjusted dietary inflammatory index (E-DII) for the associations with incident Crohn's disease (CD) and ulcerative colitis (UC) and the role of genetic susceptibility. METHODS A total of 205,706 UK Biobank participants who were aged 39-72 years and had no known CD or UC at baseline (2006-2010) were included. The E-DII score was calculated based on energy-adjusted average intakes of 33 food or nutrient items derived from up to five 24-hour dietary recalls. Multivariable Cox regression models were used estimate hazard ratios (HRs) with 95% confidence interval (CI) for incident CD and UC. RESULTS During a median 12.3 years of follow-up, 382 incident CD and 798 incident UC cases were ascertained. A higher E-DII score was not associated with risk of CD (HR Q4 VS. Q1 = 1.28, 95% CI: 0.94-1.74; P-trend = 0.09) or UC (HR Q4 VS. Q1 = 1.10, 95% CI: 0.90-1.36; P-trend = 0.17). There was an interaction between the E-DII and the polygenic risk score (PRS) for CD on incident CD (P-interaction = 0.023), with an association only among participants with a high PRS (HR Q4 VS. Q1 = 1.64, 95% CI: 1.03-2.61) (P-interaction = 0.023). As compared with the participants with a low PRS for CD and a low E-DII score, participants with high levels of both scores had a particularly higher risk of CD (HR = 3.12; 95% CI: 1.74-5.60). CONCLUSIONS The association of dietary inflammatory potential with incident CD appears to be amplified by high genetic susceptibility to CD.
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Affiliation(s)
- Ji-Mei Gu
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China
| | - Miao Zhao
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China
| | - Jie Zhu
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China
| | - Hao-Wei Tao
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China
| | - Xiao-Ping Shao
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China
| | - Li-Qiang Qin
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China
| | - Yang-Yang Ge
- Department of Radiation Oncology, The Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, 30 Tongyang North Road, Nantong, 226361, China.
| | - Guo-Chong Chen
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China.
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Zhang R, Zhang X, Lau HCH, Yu J. Gut microbiota in cancer initiation, development and therapy. SCIENCE CHINA. LIFE SCIENCES 2025; 68:1283-1308. [PMID: 39821827 DOI: 10.1007/s11427-024-2831-x] [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: 12/03/2024] [Accepted: 12/12/2024] [Indexed: 01/19/2025]
Abstract
Cancer has long been associated with genetic and environmental factors, but recent studies reveal the important role of gut microbiota in its initiation and progression. Around 13% of cancers are linked to infectious agents, highlighting the need to identify the specific microorganisms involved. Gut microbiota can either promote or inhibit cancer growth by influencing oncogenic signaling pathways and altering immune responses. Dysbiosis can lead to cancer, while certain probiotics and their metabolites may help reestablish micro-ecological balance and improve anti-tumor immune responses. Research into targeted approaches that enhance therapy with probiotics is promising. However, the effects of probiotics in humans are complex and not yet fully understood. Additionally, methods to counteract harmful bacteria are still in development. Early clinical trials also indicate that modifying gut microbiota may help manage side effects of cancer treatments. Ongoing research is crucial to understand better how gut microbiota can be used to improve cancer prevention and treatment outcomes.
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Affiliation(s)
- Ruyi Zhang
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Xiang Zhang
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Harry Cheuk Hay Lau
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Jun Yu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
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Gill T. Exploring the Mucosal Immune Response in Axial Spondyloarthritis Through Immunoglobulin A-Coated Microbiota. Rheum Dis Clin North Am 2025; 51:283-293. [PMID: 40246441 DOI: 10.1016/j.rdc.2025.01.006] [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] [Indexed: 04/19/2025]
Abstract
In this review, we focus on the mucosal immune response through Immunoglobulin A (IgA)-coated microbes and their role in gut dysbiosis in axial spondyloarthritis (axSpA) and associated inflammatory bowel disease. IgA-coated microbes contribute significantly to the microbial dysbiosis observed in axSpA, potentially driving gut inflammation and translocating outside of the gut and initiating systemic immune activation, thus contributing to disease pathogenesis. These insights will provide new avenues for understanding and treating axSpA and other immune-mediated inflammatory disorders by targeting specific host immune-microbe interactions.
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Affiliation(s)
- Tejpal Gill
- Division of Arthritis and Rheumatic Diseases, Casey Eye Insitute, Oregon Science & Health University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97229, USA.
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Huang S, Xiao H, Xiao H, Liu L, Cai S. Higher dietary live microbe intake is linked to reduced risk of metabolic syndrome and mortality: a cross-sectional and longitudinal study. Front Nutr 2025; 12:1592969. [PMID: 40365238 PMCID: PMC12069296 DOI: 10.3389/fnut.2025.1592969] [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: 03/13/2025] [Accepted: 04/15/2025] [Indexed: 05/15/2025] Open
Abstract
Background The association between dietary live microbe intake and metabolic syndrome (MetS) prevalence, as well as its impact on all-cause and cardiovascular disease (CVD) mortality in MetS patients, remains underexplored. Methods A total of 38,462 individuals from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were analyzed. Based on the live microbial level of the consumed foods, participants were divided into three dietary live microbe intake groups: low, medium, and high. Foods with medium and high live microbe content were aggregated into a medium-high consumption category. MetS was defined based on NCEP-ATP III criteria. Survey-weighted logistic regression assessed the cross-sectional association with MetS prevalence, while Cox proportional hazards models evaluated mortality risks in 12,432 individuals with MetS, among whom 2,641 all-cause and 901 CVD deaths occurred. Results Higher dietary live microbe intake was significantly associated with lower odds of MetS. Compared to the low intake group, participants in the high intake group had a 12% lower risk of MetS in the fully adjusted model (OR: 0.88; 95% CI: 0.80-0.97; p = 0.01). Among MetS components, significant inverse associations were observed for low HDL-C, elevated TG, and elevated BP. Participants with high dietary live microbe intake demonstrated a significantly lower risk of all-cause mortality (HR: 0.85; 95% CI: 0.77-0.94; p = 0.002) and CVD-specific mortality (HR: 0.71; 95% CI: 0.55-0.92; p = 0.001) compared to the low intake group. Kaplan-Meier survival curves revealed better survival probabilities in individuals with medium and high intake levels, with significant differences across groups (log-rank p < 0.005). Quantitatively, each 100g increase in MedHi foods was associated with 6% lower all-cause mortality (HR: 0.94; 95% CI: 0.90-0.99; p = 0.01) and 8% lower CVD mortality (HR: 0.92; 95% CI: 0.84-1.00; p = 0.05). Conclusion Dietary live microbe intake is inversely associated with the prevalence of MetS and its key components, particularly low HDL-C, elevated TG, and elevated BP. In individuals with MetS, higher live microbe intake is associated with reduced all-cause and CVD-specific mortality. These findings suggest that dietary live microbes are a promising modifiable factor for MetS prevention and management, as well as for improving long-term survival outcomes.
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Affiliation(s)
- Shan Huang
- Department of MICU, Guangdong Women and Children Hospital, Guangzhou, China
| | - Haixia Xiao
- Department of Obstetrics, Guangdong Women and Children Hospital, Guangzhou, China
| | - Huanshun Xiao
- Department of MICU, Guangdong Women and Children Hospital, Guangzhou, China
| | - Lu Liu
- Department of Internal Medicine, Guangdong Women and Children Hospital, Guangzhou, China
| | - Shuangming Cai
- Department of MICU, Guangdong Women and Children Hospital, Guangzhou, China
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40
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Wu X, Mei J, Qiao S, Long W, Feng Z, Feng G. Causal relationships between gut microbiota and male reproductive inflammation and infertility: Insights from Mendelian randomization. Medicine (Baltimore) 2025; 104:e42323. [PMID: 40295237 PMCID: PMC12039986 DOI: 10.1097/md.0000000000042323] [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: 06/28/2024] [Revised: 09/08/2024] [Accepted: 10/30/2024] [Indexed: 04/30/2025] Open
Abstract
The study observed interactions between gut microbiota and male reproductive health, noting that the causal relationships were previously unclear. It aimed to explore the potential cause-and-effect relationship between gut bacteria and male reproductive problems such as inflammation, infertility, and sperm functionality, using a two-sample Mendelian randomization method to examine these connections. The analysis found that certain bacterial genera, such as Erysipelatoclostridium (0.71 [0.55-0.92]), Parasutterella (0.74 [0.57-0.96]), Ruminococcaceae UCG-009 (0.77 [0.60-0.98]), and Slackia (0.69 [0.49-0.96]), showed protective effects against prostatitis. In contrast, other genera like Faecalibacterium (1.59 [1.08-2.34]), Lachnospiraceae UCG004 (1.64 [1.15-2.34]), Odoribacter (1.68 [1.01-2.81]), Paraprevotella (1.28 [1.03-1.60]), and Sutterella (1.58 [1.13-2.19]) were detrimental. Additionally, causal relationships were identified between 2 genera and orchitis and epididymitis, 3 genera and male infertility, and 5 genera and abnormal spermatozoa. Further analysis of sperm-related proteins revealed causal associations between specific bacterial genera and proteins such as SPACA3, SPACA7, SPAG11A, SPAG11B, SPATA9, SPATA20, and ZPBP4. The results remained robust after sensitivity analysis and reverse Mendelian randomization analysis. The study concluded that specific bacterial genera have causal roles in reproductive inflammation, infertility, and sperm-associated proteins. This provides a novel strategy for the early diagnosis and identification of therapeutic targets in reproductive inflammation and infertility.
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Affiliation(s)
- Xiaohong Wu
- Department of Neonatology, Guangzhou Key Laboratory of Neonatal Intestinal Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
- Department of Pediatric, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Jingwen Mei
- Department of Neonatology, Guangzhou Key Laboratory of Neonatal Intestinal Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
- Department of Pediatric, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Shicun Qiao
- Department of Neonatology, Guangzhou Key Laboratory of Neonatal Intestinal Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
- Department of Pediatric, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Wen Long
- Department of Radiology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Zhoushan Feng
- Department of Neonatology, Guangzhou Key Laboratory of Neonatal Intestinal Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
- Department of Pediatric, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Guo Feng
- Department of Neonatology, Guangzhou Key Laboratory of Neonatal Intestinal Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
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Wang H, Ali M, Zhu Y, Chen X, Lu D, Liu Y, Li K, Zhang C. Comparative analysis of gut microbiota in free range and house fed yaks from Linzhou County. Sci Rep 2025; 15:14317. [PMID: 40274860 PMCID: PMC12022119 DOI: 10.1038/s41598-025-95357-4] [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: 01/01/2025] [Accepted: 03/20/2025] [Indexed: 04/26/2025] Open
Abstract
Gut microbiota variations in response to environmental and nutritional factors are of great significance as gut microbiota plays an integral role in nutrient metabolism, immunity, health, and disease conditions. In this context, limited studies investigated variations of gut microbiota in response to different feeding systems and environmental conditions. The current study obtained fresh fecal samples from house-fed (LS) and grazing yaks (LF) from Linzhou County. 16 S rRNA amplicon sequencing of the V3-V4 and internal transcribed spacer 2 (ITS2) domains generated 16,332 bacterial and 2345 fungus amplicon sequence variants (ASVs). Alpha and beta diversity indices revealed significant variations (p > 0.05) in gut microflora between the two groups. At the phylum level, Firmicutes, Actinobacteriota, Bacteroidota, and Patescibacteria regarding bacteria, and Ascomycota and Basidiomycota regarding fungi dominated. At the genus level, UCG-005, Rikenellaceae_RC9_gut_group, Clostridium_sensu_stricto_1, g__Muribaculaceae, UCG-010, [Eubacterium]_coprostanoligenes_group, Turicibacter, Alistipes, Prevotellaceae_UCG-003, UCG-009, Blautia, dgA-11_gut_group, Candidatus_Saccharimonas dominated in LS, while Anthrobacter and Terrisporobacter dominated in the LF group. Fungal genera like Myrothecium and Plectosphaerella dominated the LS group, while Neoascochyta, Paraphaeosphaeria, and Hypocreales dominated the LF group. Also, significant variations (p > 0.05) in gene expressions were found between the two groups. These findings provide insights into yak gut microbiota adaptations and metabolic changes in response to varied environmental conditions and can provide valuable information, optimizing feeding strategies after identifying specific differences between grazing and house-fed yaks, reducing environmental impacts, and improving yaks' health and productivity in specific geographical settings.
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Affiliation(s)
- Hongzhuang Wang
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, 850009, China
| | - Munwar Ali
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China
| | - Yong Zhu
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, 850009, China
| | - Xiaoying Chen
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, 850009, China
| | - Dongyang Lu
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, 850009, China
| | - Yang Liu
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, 850009, China
| | - Kun Li
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China
| | - Chengfu Zhang
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, 850009, China.
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Zhong W, Wang K, Zarrinpar A. Mind over microbiota: neurons call the shots in the gut. Nat Metab 2025:10.1038/s42255-025-01282-1. [PMID: 40263604 DOI: 10.1038/s42255-025-01282-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/24/2025]
Affiliation(s)
- Wuling Zhong
- Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
| | - Karen Wang
- Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
| | - Amir Zarrinpar
- Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
- Division of Gastroenterology, Jennifer Moreno Department of Veterans Affairs Medical Center, La Jolla, CA, USA.
- Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
- Synthetic Biology Institute, University of California San Diego, La Jolla, CA, USA.
- Institute of Diabetes and Metabolic Health, University of California San Diego, La Jolla, CA, USA.
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Han R, Li Y, Guo Y, Ren M, Shan M, Mao T, Qi X, Li Y, Tian Z, Fu T. Alginate ameliorates hyperuricemia in mice by restoring hyperuricemia-induced renal and intestinal dysfunctions. Int J Biol Macromol 2025; 310:143422. [PMID: 40268003 DOI: 10.1016/j.ijbiomac.2025.143422] [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: 01/17/2025] [Revised: 04/16/2025] [Accepted: 04/21/2025] [Indexed: 04/25/2025]
Abstract
Alginate, a bioactive polysaccharide fermentable by gut microbiota, has been shown to effectively reduce serum uric acid levels. However, its mechanisms and the role of gut microbiota remain unclear. In this study, we explored the effects of alginate with two different molecular weights on hyperuricemia mice. Both alginates exhibited potent hypouricemic effects through ABCG2 transporter upregulation, effectively ameliorating hyperuricemia-induced renal and intestinal dysfunctions, with the low-molecular-weight alginate demonstrating enhanced bioavailability through microbial biodegradation and superior therapeutic efficacy in hyperuricemia management. Additionally, we found that alginate alleviates gut microbiota dysbiosis induced by hyperuricemia by enriching potentially beneficial bacteria. These include Limosilactobacillus and Lactobacillus, which show a significant negative correlation with serum uric acid levels. These bacteria might regulate uric acid precursors during purine metabolism, thereby reducing uric acid accumulation. In summary, this study reveals the protective effects of alginate on renal and intestinal damage in hyperuricemia mice and highlights the crucial role of gut microbiota. It provides valuable insights into the mechanisms by which gut microbiota mediate the effects of alginate.
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Affiliation(s)
- Rongshuang Han
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266001, PR China
| | - Yukun Li
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266001, PR China
| | - Yingjie Guo
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266001, PR China
| | - Minghan Ren
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266001, PR China
| | - Mengchen Shan
- Department of Gastroenterology, Qingdao Cardiovascular Hospital, Qingdao 266000, PR China
| | - Tao Mao
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266001, PR China
| | - Xingsi Qi
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266001, PR China
| | - Yupeng Li
- College of Marine Life Science, Ocean University of China, Qingdao 266003, PR China
| | - Zibin Tian
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266001, PR China.
| | - Tianyu Fu
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266001, PR China.
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Fang Z, Chang S, Niu P, Wang C, Zhang J. Multidimensional-based exploration of gut microbial and metabolite differences in patients with recurrent stroke. Neuroscience 2025; 572:35-48. [PMID: 39914520 DOI: 10.1016/j.neuroscience.2025.02.004] [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: 07/11/2024] [Revised: 01/17/2025] [Accepted: 02/02/2025] [Indexed: 03/11/2025]
Abstract
This study aims to explore the differences in gut microbes and their metabolites between patients with original and recurrent stroke, providing insights and justification for the diagnosis and prevention of ischemic stroke progression from the perspective of the gut microbiota-metabolite-brain axis. In this study, fecal samples were collected from patients with Original stroke (Os) and patients with Recurrent stroke (Rs) to assess differences in gut microbiota and to screen for different metabolites that reveal the physiological changes related to the recurrent of ischemic stroke. The results found that there was no significant change in Alpha diversity between the two groups. Beta diversity analysis revealed slight changes in community composition between two groups (Bray-Curtis), although their overall microbial abundance may not have changed (UniFrac). Compared with Os patients, Prevotella, Lachnospiraceae_UCG-010, Holdemanella, and Coprococcus were significantly depleted in the Rs group. Correlation analysis showed that the risk of stroke recurrence was negatively correlated with Lachnospiraceae_UCG-010. In Rs group, metabolites such as carbohydrates and terpene lactones were up-regulated, while those of sesquiterpenoids, triterpenoids, and fatty acids and their couplings were down-regulated. These metabolites are significantly enriched in the pathways of arachidonic acid metabolism, betaine biosynthesis, and linoleic acid metabolism. Compared with the Os, Rs was mainly characterized by minor destruction of anaerobic bacteria and significant depletion of SCFAs-producing bacteria. In addition, the related compounds involved in arachidonic acid metabolism and linoleic acid metabolism pathway may be associated with the progression of ischemic stroke.
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Affiliation(s)
- Zongwei Fang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Sijie Chang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Peiguang Niu
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Chunhua Wang
- Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jinhua Zhang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
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45
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Tang LF, Tang FL, Zhou H, Li ZK, Pi CQ, He Y, Li M. Bacillus Coagulans BC99 Protects Ionizing Radiation-Induced Intestinal Injury and Modulates Gut Microbiota and Metabolites in Mice. Mol Nutr Food Res 2025:e70057. [PMID: 40243794 DOI: 10.1002/mnfr.70057] [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: 12/12/2024] [Revised: 03/11/2025] [Accepted: 03/18/2025] [Indexed: 04/18/2025]
Abstract
The gastrointestinal tract is highly sensitive to ionizing radiation (IR), which causes radiation-induced intestinal injury (RIII). There are no effective drugs available for RIII in routine clinical treatment, which is a major limiting factor during the process of radiotherapy for pelvic abdominal malignancies. In this study, we aimed to elucidate the potential of probiotic Bacillus coagulans BC99 (B.coagulans BC99) in preventing RIII. C57BL/6J mice were gavage-administered with B.coagulans BC99 for 30 days and then exposed to a single dose of 12 Gy x-ray whole abdominal irradiation (WAI). B.coagulans BC99 treatment could mitigate RIII by preventing weight loss, maintaining the integrity of intestinal structure and barrier, improving inflammatory symptoms, modulating oxidative stress, and regulating the composition of gut microbiota, thereby reestablishing intestinal homeostasis. In addition, the potential radioprotective mechanism of B.coagulans BC99 was closely related to the gut microbiota-derived metabolites. This study offers a novel perspective for advancing probiotic-based treatments for RIII and enhancing strategies for the prevention of RIII.
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Affiliation(s)
- Lin-Feng Tang
- State Key Laboratory of Radiation Medicine and Protection, Key Laboratory of Radiation Damage and Treatment of Jiangsu Provincial Universities and Colleges, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, School of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, China
- Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Feng-Ling Tang
- Department of Oncology and Hematology, The Zhongxian People's Hospital, Chongqing, China
| | - Hao Zhou
- State Key Laboratory of Radiation Medicine and Protection, Key Laboratory of Radiation Damage and Treatment of Jiangsu Provincial Universities and Colleges, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, School of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, China
| | - Ze-Kun Li
- State Key Laboratory of Radiation Medicine and Protection, Key Laboratory of Radiation Damage and Treatment of Jiangsu Provincial Universities and Colleges, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, School of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, China
| | - Chao-Qun Pi
- MOE Engineering Center of Hematological Disease, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China
- Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
| | - Yang He
- MOE Engineering Center of Hematological Disease, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China
- Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
| | - Ming Li
- State Key Laboratory of Radiation Medicine and Protection, Key Laboratory of Radiation Damage and Treatment of Jiangsu Provincial Universities and Colleges, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, School of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, China
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Flores C, Millard S, Seekatz AM. Bridging Ecology and Microbiomes: Applying Ecological Theories in Host-associated Microbial Ecosystems. CURRENT CLINICAL MICROBIOLOGY REPORTS 2025; 12:9. [PMID: 40248762 PMCID: PMC12000275 DOI: 10.1007/s40588-025-00246-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2025] [Indexed: 04/19/2025]
Abstract
Purpose of Review This review explores the application of classical ecological theory to host-associated microbiomes during initial colonization, maintenance, and recovery. We discuss unique challenges of applying these theories to host-associated microbiomes and host factors to consider going forward. Recent Findings Recent studies applying community ecology principles to host microbiomes continue to demonstrate a role for both selective and stochastic processes in shaping host-associated microbiomes. However, ecological frameworks developed to describe dynamics during homeostasis do not necessarily apply during diseased or highly perturbed states, where large variations can potentially lead to alternate stable states. Summary Despite providing valuable insights, the application of ecological theories to host-associated microbiomes has some unique challenges. The integration of host-specific factors, such as genotype or immune dynamics in ecological models or frameworks is crucial for understanding host microbiome assembly and stability, which could improve our ability to predict microbiome outcomes and improve host health.
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Affiliation(s)
- Clara Flores
- Department of Biological Sciences, Clemson University, Life Sciences Building 157 A, 190 Collings St, Clemson, SC 29634 USA
| | - Sophie Millard
- Department of Biological Sciences, Clemson University, Life Sciences Building 157 A, 190 Collings St, Clemson, SC 29634 USA
| | - Anna M. Seekatz
- Department of Biological Sciences, Clemson University, Life Sciences Building 157 A, 190 Collings St, Clemson, SC 29634 USA
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Li S, Zhou L, Ren J, Liu J, Zhang Q, Xiao X. The role of cecal metabolites and DNA methylation in deciphering the effects of maternal genistein intake on white fat browning in adult female offspring. Food Funct 2025; 16:3090-3100. [PMID: 40146209 DOI: 10.1039/d4fo04761c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/28/2025]
Abstract
Maternal diets during pregnancy and lactation are critical determinants that regulate the metabolic homeostasis in offspring. Our previous research demonstrated that maternal genistein (GEN) intervention ameliorated the dysregulation of glucolipid metabolism induced by intrauterine overnutrition in adult offspring, accompanied by changes in the composition of gut microbiota; however, the underlying mechanisms remain unclear. Here, we used a maternal overnutrition model induced by excess energy intake before and throughout pregnancy and lactation, with maternal GEN administered during the same period. The female offspring were raised on a standard chow diet until sacrificed at 24 weeks. The mRNA levels of browning markers were quantified in inguinal subcutaneous adipose tissues, followed by methylation analysis via the MassArray method. Cecal contents were collected for untargeted metabolomic analysis and a target quantitative analysis of methionine cycle metabolites. Spearman correlation analyses were used to assess whether cecal metabolites are involved in the methylation of browning-related genes and influence their expression. The results showed that maternal GEN supplementation reversed the downregulation of browning markers caused by perinatal high-fat diets in adult female offspring, consistent with a reduction in their methylation levels. Subsequently, we also found that maternal GEN consumption altered cecal metabolite profiles in offspring, promoting the production of bile acids, potent regulators of glucolipid metabolism, and reducing metabolites involved in the methionine cycle, key methyl donors for the methylation process. Furthermore, the abundances of these metabolites were significantly correlated with the methylation and expression levels of browning markers. Overall, this discovery suggested that maternal GEN intake decreased the methylation level of browning markers and induced browning in white adipose tissue of offspring, which correlated with alterations in cecal metabolites. We provide a novel theoretical basis for GEN as a promising nutritional supplement to break the vicious cycle of maternal metabolic disturbances being transmitted to offspring.
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Affiliation(s)
- Shunhua Li
- Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Liyuan Zhou
- Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China
| | - Jing Ren
- Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Jieying Liu
- Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China.
- Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Qian Zhang
- Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Xinhua Xiao
- Key Laboratory of Endocrinology of National Health Commission, Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China.
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Abdeen SK, Mastandrea I, Stinchcombe N, Puschhof J, Elinav E. Diet-microbiome interactions in cancer. Cancer Cell 2025; 43:680-707. [PMID: 40185096 DOI: 10.1016/j.ccell.2025.03.013] [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: 01/07/2025] [Revised: 02/26/2025] [Accepted: 03/11/2025] [Indexed: 04/07/2025]
Abstract
Diet impacts cancer in diverse manners. Multiple nutritional effects on tumors are mediated by dietary modulation of commensals, residing in mucosal surfaces and possibly also within the tumor microenvironment. Mechanistically understanding such diet-microbiome-host interactions may enable to develop precision nutritional interventions impacting cancer development, dissemination, and treatment responses. However, data-driven nutritional strategies integrating diet-microbiome interactions are infrequently incorporated into cancer prevention and treatment schemes. Herein, we discuss how dietary composition affects cancer-related processes through alterations exerted by specific nutrients and complex foods on the microbiome. We highlight how dietary timing, including time-restricted feeding, impacts microbial function in modulating cancer and its therapy. We review existing and experimental nutritional approaches aimed at enhancing microbiome-mediated cancer treatment responsiveness while minimizing adverse effects, and address challenges and prospects in integrating diet-microbiome interactions into precision oncology. Collectively, mechanistically understanding diet-microbiome-host interactomes may enable to achieve a personalized and microbiome-informed optimization of nutritional cancer interventions.
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Affiliation(s)
- Suhaib K Abdeen
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel
| | | | - Nina Stinchcombe
- Division of Microbiome & Cancer, DKFZ, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany; Junior Research Group Epithelium Microbiome Interactions, DKFZ, Heidelberg, Germany
| | - Jens Puschhof
- Division of Microbiome & Cancer, DKFZ, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany; Junior Research Group Epithelium Microbiome Interactions, DKFZ, Heidelberg, Germany.
| | - Eran Elinav
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel; Division of Microbiome & Cancer, DKFZ, Heidelberg, Germany.
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Martino C, Kellman BP, Sandoval DR, Clausen TM, Cooper R, Benjdia A, Soualmia F, Clark AE, Garretson AF, Marotz CA, Song SJ, Wandro S, Zaramela LS, Salido RA, Zhu Q, Armingol E, Vázquez-Baeza Y, McDonald D, Sorrentino JT, Taylor B, Belda-Ferre P, Das P, Ali F, Liang C, Zhang Y, Schifanella L, Covizzi A, Lai A, Riva A, Basting C, Broedlow CA, Havulinna AS, Jousilahti P, Estaki M, Kosciolek T, Kuplicki R, Victor TA, Paulus MP, Savage KE, Benbow JL, Spielfogel ES, Anderson CAM, Martinez ME, Lacey JV, Huang S, Haiminen N, Parida L, Kim HC, Gilbert JA, Sweeney DA, Allard SM, Swafford AD, Cheng S, Inouye M, Niiranen T, Jain M, Salomaa V, Zengler K, Klatt NR, Hasty J, Berteau O, Carlin AF, Esko JD, Lewis NE, Knight R. SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx. mBio 2025; 16:e0401524. [PMID: 39998226 PMCID: PMC11980591 DOI: 10.1128/mbio.04015-24] [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: 12/23/2024] [Accepted: 01/30/2025] [Indexed: 02/26/2025] Open
Abstract
The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa are known to modify. To explore human gut HS-modifying bacterial abundances and how their presence may impact SARS-CoV-2 infection, we developed a task-based analysis of proteoglycan degradation on large-scale shotgun metagenomic data. We observed that gut bacteria with high predicted catabolic capacity for HS differ by age and sex, factors associated with coronavirus disease 2019 (COVID-19) severity, and directly by disease severity during/after infection, but do not vary between subjects with COVID-19 comorbidities or by diet. Gut commensal bacterial HS-modifying enzymes reduce spike protein binding and infection of authentic SARS-CoV-2, suggesting that bacterial grooming of the GI mucosa may impact viral susceptibility.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019, can infect the gastrointestinal (GI) tract, and individuals who exhibit GI symptoms often have more severe disease. The GI tract's glycocalyx, a component of the mucosa covering the large intestine, plays a key role in viral entry by binding SARS-CoV-2's spike protein via heparan sulfate (HS). Here, using metabolic task analysis of multiple large microbiome sequencing data sets of the human gut microbiome, we identify a key commensal human intestinal bacteria capable of grooming glycocalyx HS and modulating SARS-CoV-2 infectivity in vitro. Moreover, we engineered the common probiotic Escherichia coli Nissle 1917 (EcN) to effectively block SARS-CoV-2 binding and infection of human cell cultures. Understanding these microbial interactions could lead to better risk assessments and novel therapies targeting viral entry mechanisms.
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Affiliation(s)
- Cameron Martino
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
| | - Benjamin P. Kellman
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, California, USA
| | - Daniel R. Sandoval
- Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California, USA
| | - Thomas Mandel Clausen
- Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California, USA
- Copenhagen Center for Glycomics, Department of Molecular and Cellular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Robert Cooper
- Department of Bioengineering, University of California San Diego, La Jolla, California, USA
| | - Alhosna Benjdia
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, 78350, Jouy-en-Josas, France
| | - Feryel Soualmia
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, 78350, Jouy-en-Josas, France
- Sorbonne Université, Faculty of Sciences and Engineering, IBPS, UMR 8263 CNRS-SU, ERL INSERM U1345, Development, Adaptation and Ageing, F-75252 Paris, France
| | - Alex E. Clark
- Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Aaron F. Garretson
- Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Clarisse A. Marotz
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
| | - Se Jin Song
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
| | - Stephen Wandro
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
| | - Livia S. Zaramela
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Department of Biochemistry, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Rodolfo A. Salido
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
- Department of Bioengineering, University of California San Diego, La Jolla, California, USA
| | - Qiyun Zhu
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- School of Life Sciences, Arizona State University, Tempe, Arizona, USA
| | - Erick Armingol
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, California, USA
| | - Yoshiki Vázquez-Baeza
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
- Jacobs School of Engineering, University of California San Diego, La Jolla, California, USA
| | - Daniel McDonald
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
| | - James T. Sorrentino
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, California, USA
| | - Bryn Taylor
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA
| | - Pedro Belda-Ferre
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
| | - Promi Das
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, USA
| | - Farhana Ali
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
| | - Chenguang Liang
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Department of Bioengineering, University of California San Diego, La Jolla, California, USA
- Merck & Co., Inc., Rahway, NJ, 07065, USA
| | - Yujie Zhang
- Department of Bioengineering, University of California San Diego, La Jolla, California, USA
- Department of Biological & Medical Informatics, University of California San Francisco, School of Pharmacy, San Francisco, California, USA
| | - Luca Schifanella
- Department of Surgery, Division of Surgical Outcomes and Precision Medicine Research, Medical School, University of Minnesota, Minneapolis, Minnesota, USA
- National Institutes of Health, National Cancer Institute, Center for Cancer Research, Animal Models and Retroviral Vaccine Section, Bethesda, Maryland, USA
| | - Alice Covizzi
- Department of Infectious diseases, Luigi Sacco Hospital, Milan and Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Milan, Italy
| | - Alessia Lai
- Department of Infectious diseases, Luigi Sacco Hospital, Milan and Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Milan, Italy
| | - Agostino Riva
- Department of Infectious diseases, Luigi Sacco Hospital, Milan and Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Milan, Italy
| | - Christopher Basting
- Department of Surgery, Division of Surgical Outcomes and Precision Medicine Research, Medical School, University of Minnesota, Minneapolis, Minnesota, USA
| | - Courtney Ann Broedlow
- Department of Surgery, Division of Surgical Outcomes and Precision Medicine Research, Medical School, University of Minnesota, Minneapolis, Minnesota, USA
| | - Aki S. Havulinna
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki and Turku, Finland
- Institute for Molecular Medicine Finland, FIMM - HiLIFE, Helsinki, Finland
| | - Pekka Jousilahti
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki and Turku, Finland
| | - Mehrbod Estaki
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
| | - Tomasz Kosciolek
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Sano Centre for Computational Medicine, Krakow, Poland
| | - Rayus Kuplicki
- Laureate Institute for Brain Research, Tulsa, Oklahoma, USA
| | | | | | - Kristen E. Savage
- Division of Health Analytics, Department of Computational and Quantitative Medicine, City of Hope, Duarte, California, USA
| | - Jennifer L. Benbow
- Division of Health Analytics, Department of Computational and Quantitative Medicine, City of Hope, Duarte, California, USA
- UC Health Data Warehouse, University of California Irvine, Irvine, California, USA
| | - Emma S. Spielfogel
- Division of Health Analytics, Department of Computational and Quantitative Medicine, City of Hope, Duarte, California, USA
| | - Cheryl A. M. Anderson
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California, USA
| | - Maria Elena Martinez
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California, USA
| | - James V. Lacey
- Division of Health Analytics, Department of Computational and Quantitative Medicine, City of Hope, Duarte, California, USA
| | - Shi Huang
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
- Faculty of Dentistry, The University of Hong Kong, Hong Kong, China
| | - Niina Haiminen
- IBM T. J. Watson Research Center, Yorktown Heights, New York, USA
| | - Laxmi Parida
- IBM T. J. Watson Research Center, Yorktown Heights, New York, USA
| | - Ho-Cheol Kim
- AI and Cognitive Software, IBM Research-Almaden, San Jose, California, USA
| | - Jack A. Gilbert
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
- Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, USA
| | - Daniel A. Sweeney
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Sarah M. Allard
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, USA
| | - Austin D. Swafford
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
- International Biomedical Research Alliance, Bethesda, Maryland, USA
| | - Susan Cheng
- Division of Cardiology, Brigham and Women’s Hospital, Boston, Massachusetts, USA
- Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Michael Inouye
- Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, United Kingdom
- Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Australia
- Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Teemu Niiranen
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki and Turku, Finland
- Division of Medicine, Turku University Hospital and University of Turku, Turku, Finland
| | - Mohit Jain
- Department of Pharmacology, University of California, San Diego, La Jolla, California, USA
| | - Veikko Salomaa
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki and Turku, Finland
| | - Karsten Zengler
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
- Department of Bioengineering, University of California San Diego, La Jolla, California, USA
| | - Nichole R. Klatt
- Department of Surgery, Division of Surgical Outcomes and Precision Medicine Research, Medical School, University of Minnesota, Minneapolis, Minnesota, USA
| | - Jeff Hasty
- Department of Bioengineering, University of California San Diego, La Jolla, California, USA
- Molecular Biology Section, Division of Biological Science, University of California San Diego, La Jolla, California, USA
| | - Olivier Berteau
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, 78350, Jouy-en-Josas, France
| | - Aaron F. Carlin
- Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Jeffrey D. Esko
- Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California, USA
- Glycobiology Research and Training Center, University of California San Diego, La Jolla, California, USA
| | - Nathan E. Lewis
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
- Department of Bioengineering, University of California San Diego, La Jolla, California, USA
- Jacobs School of Engineering, University of California San Diego, La Jolla, California, USA
- Center for Molecular Medicine, Complex Carbohydrate Research Center, and Dept of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, USA
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark
| | - Rob Knight
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
- Department of Bioengineering, University of California San Diego, La Jolla, California, USA
- Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, USA
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Zheng S, Lou Y, Zhang J, Wang Y, Lv L. Association of dietary live microbe intake with all-cause and cardiovascular mortality in an older population: Evidence from NHANES 2003-2018. Arch Gerontol Geriatr 2025; 131:105741. [PMID: 39756187 DOI: 10.1016/j.archger.2024.105741] [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: 10/20/2024] [Revised: 12/12/2024] [Accepted: 12/30/2024] [Indexed: 01/07/2025]
Abstract
BACKGROUND The relationship between dietary live microbe intake, non-dietary prebiotics/probiotics, and mortality in older adults remains unclear. METHODS Participants from the National Health and Nutrition Examination Survey 2003-2018 were included. Participants were categorized into three groups based on estimated live microbe intake: low, medium, and high. Additionally, they were divided by their consumption of foods with medium or high microbial content. Text mining was employed to identify the use of non-dietary prebiotics and probiotics by analyzing the names and ingredients of dietary supplements and drugs. Associations between live microbe intake, non-dietary prebiotics/probiotics, and all-cause or cardiovascular mortality were assessed using Kaplan-Meier survival curves and Cox regression models. Inverse Probability of Treatment Weighting was used for sensitivity analysis RESULT: A total of 7882 participants were included in the study. During a mean follow-up of 8.08 years, all-cause mortality was 18 % lower in older adults with high dietary live microbe intake in fully adjusted models (HR, 0.82; 95 %CI 0.70-0.96), and cardiovascular mortality was reduced by 23 % (HR, 0.77; 95 %CI 0.61-0.98). The risk of all-cause mortality was reduced by 21 % in the G3 group compared with the G1 group (HR, 0.79; 95 % CI 0.69-0.89) and a 29 % reduction in the risk of cardiovascular disease-specific death (HR, 0.71;95 %CI 0.59-0.86). In addition, we also observed that nondietary prebiotic and probiotic supplement intake was also associated with a reduced risk of mortality in an older US population. CONCLUSION In older U.S. adults, higher dietary live microorganisms and non-dietary probiotics/prebiotics intake was associated with a reduced risk of all-cause and cardiovascular mortality.
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Affiliation(s)
- Shuang Zheng
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China; Department of Pathology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Yanqing Lou
- Department of Pathology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, Zhejiang Province, China; Department of Pathology, The Second People's Hospital of Fuyang, Hangzhou, Zhejiang Province, China
| | - Jiali Zhang
- Department of Pathology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Yu Wang
- Department of Pathology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, Zhejiang Province, China; Department of Pathology, Maternal and child health hospital of Changxing County, Huzhou, Zhejiang Province, China
| | - Lugang Lv
- Department of Laboratory Medicine, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, Zhejiang Province, China.
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