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Wang L, Chen X, Pollock NR, Villafuerte Gálvez JA, Alonso CD, Wang D, Daugherty K, Xu H, Yao J, Chen Y, Kelly CP, Cao Y. Metagenomic analysis reveals distinct patterns of gut microbiota features with diversified functions in C. difficile infection (CDI), asymptomatic carriage and non-CDI diarrhea. Gut Microbes 2025; 17:2505269. [PMID: 40366862 PMCID: PMC12080279 DOI: 10.1080/19490976.2025.2505269] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 03/12/2025] [Accepted: 05/07/2025] [Indexed: 05/16/2025] Open
Abstract
Clostridioides difficile infection (CDI) has been recognized as a leading cause of healthcare-associated infections and a considerable threat to public health globally. Increasing evidence suggests that the gut microbiota plays a key role in the pathogenesis of CDI. The taxonomic composition and functional capacity of the gut microbiota associated with CDI have not been studied systematically. Here, we performed a comprehensive shotgun metagenomic sequencing in a well-characterized human cohort to reveal distinct patterns of gut microbiota and potential functional features associated with CDI. Fecal samples were collected from 104 inpatients, including : (1) patients with clinically significant diarrhea and positive nucleic acid amplification testing (NAAT) and received CDI treatment (CDI, n = 47); (2) patients with positive stool NAAT but without diarrhea (Carrier, n = 17); (3) patients with negative stool NAAT but with diarrhea (Diarrhea, n = 14); and (4) patients with negative stool NAAT and without diarrhea (Control, n = 26). Downstream statistical analyses (including alpha and beta diversity analysis, differential abundance analysis, correlation network analysis, and potential functional analysis) were then performed. The gut microbiota in the Control group showed higher Chao1 index (p < 0.05), while Shannon index at KEGG module level was higher in CDI than in Carrier and Control (p < 0.05). Beta diversity for species composition differed significantly between CDI vs Carrier/Control cohorts (p < 0.05). Microbial Linear discriminant analysis Effect Size and ANCOM analysis both identified 8 species (unclassified_f_Enterobacteriaceae, Veillonella_parvula, unclassified_g_Klebsiella and etc.) were enriched in CDI, Enterobacter_aerogenes was enriched in Diarrhea, Collinsella_aerofaciens, Collinsella_sp_4_8_47FAA, Collinsella_tanakaei and Collinsella_sp_CAG_166 were enriched in Control (LDA >3.0, adjusted p < 0.05). Correlation network complexity was higher in CDI with more negative correlations than in other three cohorts. Modules involved in iron complex transport system (M00240) was enriched in CDI, ABC-2 type transport system (M00254), aminoacyl-tRNA biosynthesis (M00359), histidine biosynthesis (M00026) and inosine monophosphate biosynthesis (M00048) were enriched in Carrier, ribosome (M00178 and M00179) was enriched in Diarrhea, fluoroquinolone resistance (M00729) and aminoacyl-tRNA biosynthesis (M00360) were enriched in Control (LDA > 2.5, adjusted p < 0.05). Resistance functions of acriflavine and glycylcycline were enriched in CDI, while resistance function of bacitracin was enriched in Carrier (LDA > 3.0, adjusted p < 0.05), and the contributions of phylum and species to resistance functions differed among the four groups. Our results reveal alterations of gut microbiota composition and potential functions among four groups of differential colonization/infection status of Clostridioides difficile. These findings support the potential roles of gut microbiota and their potential functions in the pathogenesis of CDI.
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Affiliation(s)
- Lamei Wang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Xinhua Chen
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Nira R. Pollock
- Division of Infectious Disease, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Department of Laboratory Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Javier A. Villafuerte Gálvez
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Carolyn D. Alonso
- Division of Infectious Disease, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Dangdang Wang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Kaitlyn Daugherty
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Hua Xu
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Junhu Yao
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Yulin Chen
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Ciaran P. Kelly
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Yangchun Cao
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Jimenez-Sanchez M, Celiberto LS, Yang H, Sham HP, Vallance BA. The gut-skin axis: a bi-directional, microbiota-driven relationship with therapeutic potential. Gut Microbes 2025; 17:2473524. [PMID: 40050613 PMCID: PMC11901370 DOI: 10.1080/19490976.2025.2473524] [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: 10/22/2024] [Revised: 01/20/2025] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
This review explores the emerging term "gut-skin axis" (GSA), describing the bidirectional signaling that occurs between the skin and the gastrointestinal tract under both homeostatic and disease conditions. Central to GSA communication are the gut and skin microbiota, the microbial communities that colonize these barrier surfaces. By influencing diverse host pathways, including innate immune, vitamin D receptor, and Aryl hydrocarbon receptor signaling, a balanced microbiota contributes to both tissue homeostasis and host defense. In contrast, microbiota imbalance, or dysbiosis at one site, can lead to local barrier dysfunction, resulting in the activation of signaling pathways that can disrupt tissue homeostasis at the other site, potentially leading to inflammatory skin conditions such as atopic dermatitis and psoriasis, or gut diseases like Inflammatory Bowel Disease. To date, most research on the GSA has examined the impact of the gut microbiota and diet on skin health, but recent studies show that exposing the skin to ultraviolet B-light can beneficially modulate both the gut microbiome and intestinal health. Thus, despite the traditional focus of clinicians and researchers on these organ systems as distinct, the GSA offers new opportunities to better understand the pathogenesis of cutaneous and gastrointestinal diseases and promote health at both sites.
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Affiliation(s)
- Maira Jimenez-Sanchez
- Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, Canada
| | - Larissa S. Celiberto
- Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, Canada
| | - Hyungjun Yang
- Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, Canada
| | - Ho Pan Sham
- Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, Canada
| | - Bruce A. Vallance
- Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, Canada
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Schoonakker MP, van Peet PG, van den Burg EL, Numans ME, Ducarmon QR, Pijl H, Wiese M. Impact of dietary carbohydrate, fat or protein restriction on the human gut microbiome: a systematic review. Nutr Res Rev 2025; 38:238-255. [PMID: 38602133 DOI: 10.1017/s0954422424000131] [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: 04/12/2024]
Abstract
Restriction of dietary carbohydrates, fat and/or protein is often used to reduce body weight and/or treat (metabolic) diseases. Since diet is a key modulator of the human gut microbiome, which plays an important role in health and disease, this review aims to provide an overview of current knowledge of the effects of macronutrient-restricted diets on gut microbial composition and metabolites. A structured search strategy was performed in several databases. After screening for inclusion and exclusion criteria, thirty-six articles could be included. Data are included in the results only when supported by at least three independent studies to enhance the reliability of our conclusions. Low-carbohydrate (<30 energy%) diets tended to induce a decrease in the relative abundance of several health-promoting bacteria, including Bifidobacterium, as well as a reduction in short-chain fatty acid (SCFA) levels in faeces. In contrast, low-fat diets (<30 energy%) increased alpha diversity, faecal SCFA levels and abundance of some beneficial bacteria, including Faecalibacterium prausnitzii. There were insufficient data to draw conclusions concerning the effects of low-protein (<10 energy%) diets on gut microbiota. Although the data of included studies unveil possible benefits of low-fat and potential drawbacks of low-carbohydrate diets for human gut microbiota, the diversity in study designs made it difficult to draw firm conclusions. Using a more uniform methodology in design, sample processing and sharing raw sequence data could foster our understanding of the effects of macronutrient restriction on gut microbiota composition and metabolic dynamics relevant to health. This systematic review was registered at https://www.crd.york.ac.uk/prospero as CRD42020156929.
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Affiliation(s)
- Marjolein P Schoonakker
- Department of Public Health and Primary Care, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
| | - Petra G van Peet
- Department of Public Health and Primary Care, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
| | - Elske L van den Burg
- Department of Public Health and Primary Care, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
| | - Mattijs E Numans
- Department of Public Health and Primary Care, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
| | - Quinten R Ducarmon
- Department of Medical Microbiology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
| | - Hanno Pijl
- Department of Public Health and Primary Care, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
- Department of Internal Medicine, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
| | - Maria Wiese
- Department of Medical Microbiology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
- Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands
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Cresci GAM. Understanding how foods and enteral feedings influence the gut microbiome. Nutr Clin Pract 2025; 40:555-574. [PMID: 40051043 PMCID: PMC12049572 DOI: 10.1002/ncp.11285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 01/09/2025] [Accepted: 02/06/2025] [Indexed: 05/06/2025] Open
Abstract
The gut microbiome supports both gut and overall health. Diet is known to be one of the driving factors that influences the gut microbiome. The foods we eat, the dietary and nondietary components they contain, various food consumption patterns, and the ratio of nutrients consumed have been shown to impact gut microbiome composition and function. Studies indicate that many acute and chronic diseases are associated with alterations to the gut microbiome. There are many patients who rely on enteral tube feeding for their nutrition support. More recently, enteral tube feeding formulations of "real food" have become commercially available. However, little is known about how enteral tube feeding impacts the gut microbiome in patients requiring this specialized form of nutrition therapy. This review summarizes the existing evidence regarding the food sources of commonly consumed macronutrients and their impact on the gut microbiome. Also presented is what is known regarding "standard" and real food enteral formulations on the gut microbiome. Existing evidence is suggestive that real food enteral formulations positively impact the gut microbiome. Still, more research is needed on ready-to-feed formulations, particularly in patients with various clinical conditions, and how gut microbiome modulation impacts clinical outcomes.
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Affiliation(s)
- Gail A. M. Cresci
- Department of GastroenterologyHepatology, and Nutrition, Digestive Disease Institute, Cleveland ClinicClevelandOhioUSA
- Department of Inflammation and ImmunityLerner Research Institute, Cleveland ClinicClevelandOhioUSA
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Rose AE, Fansler RT, Zhu W. Commensal resilience: ancient ecological lessons for the modern microbiota. Infect Immun 2025:e0050224. [PMID: 40387449 DOI: 10.1128/iai.00502-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/20/2025] Open
Abstract
The gut microbiota constitutes a complex ecosystem essential for host health, offering metabolic support, modulating the immune system, and protecting against pathogens. However, this community faces constant destabilizing challenges, including dietary changes, antibiotics, and enteric infection. Prolonged microbiota imbalance or dysbiosis can exacerbate intestinal disease states, including inflammatory bowel disease and colorectal cancer. Understanding the mechanisms that sustain microbiota resilience in the face of these imbalances is crucial for maintaining host health and developing effective therapeutics. This review explores microbiota resilience through the lens of an ecological model, emphasizing the interplay between microbial communities and host-driven environmental controls. We highlight two critical factors shaping microbiota resilience: oxygen tension and iron availability-challenges encountered by ancient anaerobic organisms during early evolutionary history, from which the predominant members of the microbiota have descended. Disruptions in intestinal anaerobiosis during inflammation increase luminal oxygen levels, favoring pro-inflammatory facultative anaerobes and depleting obligately anaerobic commensals. Simultaneously, host nutritional immunity restricts iron availability, further challenging commensal survival. This dual environmental challenge of rising oxygen tension and reduced iron availability is a convergent outcome of a diverse array of perturbations, from pathogen invasion to antibiotic treatment. By highlighting these conserved downstream environmental challenges rather than the specific upstream perturbations, this ecological view offers a focused framework for understanding microbiota resilience. This perspective not only enhances our understanding of host-microbiota interactions but also informs therapeutic strategies to foster resilience and support host health.
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Affiliation(s)
- Abigail E Rose
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Ryan T Fansler
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Wenhan Zhu
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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6
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Shah T, Guo X, Ahmad G, Ishaq M, Din AU, Sardar S, Ding L. Exploring age-related changes in gut bacterial community composition of yak: insights from different age groups. BMC Microbiol 2025; 25:301. [PMID: 40380119 PMCID: PMC12082988 DOI: 10.1186/s12866-025-04011-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 04/28/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND The Qinghai-Tibetan Plateau (QTP) offers one of the most extreme environments for yaks (Bos grunniens). The yak is an indigenous species, and the wild yak was domesticated on the QTP. The gut microbiota plays a vital role in health and animal performance. However, little is known about the progression of gut microbes in different age developmental stages of domesticated yaks. METHOD We used the 16 S rRNA gene sequencing method to explore the progression of the fecal bacterial microbiota of 18 different confined domestic yaks at two developmental stages: 3 to 5 years (GT35) and 6 to 8 years (GT68). RESULTS We found significant differences in gut bacterial communities between the two age groups. The diversity of the gut bacterial community was significantly lower in the GT35 group, which reached stability with age. Bacteroidetes and Firmicutes were the two dominant phyla between the two age groups. Phylum Firmicutes was significantly higher in the GT68 group, and Proteobacteria, Spirochaetes, Tenericutes, and Actinobacteria were highly abundant in the GT35 age group. Genera Bacteroides, Alloprevotella, and Anaerovibrio were abundant in the GT35 group. The short-chain fatty acid (SCFA) producing bacteria Rikenellaceae showed higher abundance in GT35. The core bacterial microbiota of the GT68 age group was dominated by Ruminococcaceae and Rikenellaceae. The gut bacterial community has a great variation between the groups. Based on the exploration of dynamic changes in the gut bacterial community at different ages, our results illustrate that yaks undergo a process of reaching stability and maturity as they age.
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Affiliation(s)
- Tariq Shah
- Sichuan Provincial Forest and Grassland Key Laboratory of Alpine Grassland Conservation and Utilization of Tibetan Plateau, Institute of Qinghai-Tibetan Plateau, College of Grassland Resources, Southwest Minzu University, Chengdu, 610041, China
- State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Ministry of Agriculture and Rural Affairs, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, 730020, China
| | - Xusheng Guo
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou, 730000, PR China
| | - Gulraiz Ahmad
- State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Ministry of Agriculture and Rural Affairs, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, 730020, China
| | - Muhammad Ishaq
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou, 730000, PR China
| | - Ahmad Ud Din
- Plants for Human Health Institute, North Carolina State University, Kannapolis, NC, USA
| | - Sadia Sardar
- Department of Microbiology, Women University, Swabi, KP, Pakistan
| | - Luming Ding
- Sichuan Provincial Forest and Grassland Key Laboratory of Alpine Grassland Conservation and Utilization of Tibetan Plateau, Institute of Qinghai-Tibetan Plateau, College of Grassland Resources, Southwest Minzu University, Chengdu, 610041, China.
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Veseli I, Chen YT, Schechter MS, Vanni C, Fogarty EC, Watson AR, Jabri B, Blekhman R, Willis AD, Yu MK, Fernàndez-Guerra A, Füssel J, Eren AM. Microbes with higher metabolic independence are enriched in human gut microbiomes under stress. eLife 2025; 12:RP89862. [PMID: 40377187 PMCID: PMC12084026 DOI: 10.7554/elife.89862] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2025] Open
Abstract
A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. A classifier we trained using the normalized copy numbers of 33 HMI-associated metabolic modules not only distinguished states of health vs IBD, but also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments.
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Affiliation(s)
- Iva Veseli
- Biophysical Sciences Program, The University of ChicagoChicagoUnited States
- Department of Medicine, The University of ChicagoChicagoUnited States
| | - Yiqun T Chen
- Data Science Institute and Department of Biomedical Data Science, Stanford UniversityStanfordUnited States
| | - Matthew S Schechter
- Department of Medicine, The University of ChicagoChicagoUnited States
- Committee on Microbiology, The University of ChicagoChicagoUnited States
| | - Chiara Vanni
- MARUM Center for Marine Environmental Sciences, University of BremenBremenGermany
| | - Emily C Fogarty
- Department of Medicine, The University of ChicagoChicagoUnited States
- Committee on Microbiology, The University of ChicagoChicagoUnited States
| | - Andrea R Watson
- Department of Medicine, The University of ChicagoChicagoUnited States
- Committee on Microbiology, The University of ChicagoChicagoUnited States
| | - Bana Jabri
- Department of Medicine, The University of ChicagoChicagoUnited States
| | - Ran Blekhman
- Department of Medicine, The University of ChicagoChicagoUnited States
| | - Amy D Willis
- Department of Biostatistics, University of WashingtonSeattleUnited States
| | - Michael K Yu
- Toyota Technological Institute at ChicagoChicagoUnited States
| | - Antonio Fernàndez-Guerra
- Lundbeck Foundation GeoGenetics Centre, GLOBE Institute, University of CopenhagenCopenhagenDenmark
| | - Jessika Füssel
- Department of Medicine, The University of ChicagoChicagoUnited States
- Institute for Chemistry and Biology of the Marine Environment, University of OldenburgOldenburgGermany
| | - A Murat Eren
- Department of Medicine, The University of ChicagoChicagoUnited States
- Institute for Chemistry and Biology of the Marine Environment, University of OldenburgOldenburgGermany
- Marine ‘Omics Bridging Group, Max Planck Institute for Marine MicrobiologyBremenGermany
- Helmholtz Institute for Functional Marine BiodiversityOldenburgGermany
- Alfred Wegener Institute for Polar and Marine ResearchBremerhavenGermany
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8
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Yau R, Pavloudi C, Zeng Y, Saw J, Eleftherianos I. Infection with the entomopathogenic nematodes Steinernema alters the Drosophila melanogaster larval microbiome. PLoS One 2025; 20:e0323657. [PMID: 40378358 DOI: 10.1371/journal.pone.0323657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Accepted: 04/11/2025] [Indexed: 05/18/2025] Open
Abstract
The fruit fly Drosophila melanogaster is a vital model for studying the microbiome due to the availability of genetic resources and procedures. To understand better the importance of microbial composition in shaping immune modulation, we can investigate the role of the microbiota through parasitic infection. For this, we use entomopathogenic nematodes (EPN) of the genus Steinernema which exhibit remarkable ability to efficiently infect a diverse array of insect species, facilitated by the mutualistic bacteria Xenorhabdus found within their gut. To examine the microbiome changes in D. melanogaster larvae in response to Steinernema nematode infection, D. melanogaster late second to early third instar larvae were exposed separately to S. carpocapsae and S. hermaphroditum infective juveniles. We have found that S. carpocapsae infective juveniles are more pathogenic to D. melanogaster larvae compared to the closely related S. hermaphroditum. Our microbiome analysis also indicates substantial changes in the size and composition of the D. melanogaster larval microbiome during infection with either nematode species compared to the uninfected controls. Our results serve as a foundation for future studies to elucidate the entomopathogenic-specific effector molecules that alter the D. melanogaster microbiome and understand the role of the microbiome in regulating insect anti-nematode immune processes.
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Affiliation(s)
- Raymond Yau
- Department of Biological Sciences, The George Washington University, Washington, DC, United States of America
| | - Christina Pavloudi
- Department of Biological Sciences, The George Washington University, Washington, DC, United States of America
- European Marine Biological Resource Centre-European Research Infrastructure Consortium (EMBRC-ERIC), Paris, France
| | - Yingying Zeng
- Department of Biological Sciences, The George Washington University, Washington, DC, United States of America
| | - Jimmy Saw
- Department of Biological Sciences, The George Washington University, Washington, DC, United States of America
| | - Ioannis Eleftherianos
- Department of Biological Sciences, The George Washington University, Washington, DC, United States of America
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Ha YJ, Hwang SJ, Hong S, Kim J, Kim M, Lee GS, Lee SH, Kim H, Lee BS, In An H, Kim KH, Lee W, Lee HJ, Kim CS. Erythromycin Stress Upregulates Antiangiogenic Metabolites in the Gut Bacterium Aneurinibacillus aneurinilyticus. J Am Chem Soc 2025; 147:16459-16470. [PMID: 40305844 DOI: 10.1021/jacs.5c03174] [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: 05/02/2025]
Abstract
The interplay among antibiotics, gut microbiota, and disease pathogenesis remains poorly understood, particularly in the context of rare gut bacteria. This study identifies a novel correlation between erythromycin-induced stress and the production of antiangiogenic metabolites in Aneurinibacillus aneurinilyticus, a human gut bacterium. We report the isolation and structural characterization of aneuristatin (1), a metabolite featuring a unique pyrrolo[1,2-a]pyrazine scaffold, along with seven structurally related metabolites (2-8) from A. aneurinilyticus ATCC 12856T. These metabolites were upregulated via the erythromycin-induced activation of the arnA biosynthetic gene. Aneuristatin (1) enhanced prolyl hydroxylase activity, promoting hypoxia-inducible factor-1α (HIF-1α) degradation and reducing downstream targets, including VEGF and EPO. It also exhibited antioxidant effects by reducing ROS levels under hypoxia. Additionally, it inhibited angiogenesis in HUVECs and zebrafish and effectively reduced inflammation, fibrosis, and angiogenesis in a mouse corneal injury model. Our study establishes a molecular basis for the potential of erythromycin-induced aneuristatin (1) to prevent or treat angiogenesis-related diseases such as cancer.
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Affiliation(s)
- Young Jun Ha
- Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Su Jung Hwang
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Subin Hong
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Jonghwan Kim
- Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Minji Kim
- Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Gyu Sung Lee
- Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Seung Hwan Lee
- Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Hyemin Kim
- Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Bum Soo Lee
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Hye In An
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Ki Hyun Kim
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Wonsik Lee
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Hyo-Jong Lee
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Chung Sub Kim
- Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
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10
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Castañeda S, Tomiak J, Andersen LO, Acosta CP, Vasquez-A LR, Stensvold CR, Ramírez JD. Impact of Blastocystis carriage and colonization intensity on gut microbiota composition in a non-westernized rural population from Colombia. PLoS Negl Trop Dis 2025; 19:e0013111. [PMID: 40354411 DOI: 10.1371/journal.pntd.0013111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 05/03/2025] [Indexed: 05/14/2025] Open
Abstract
BACKGROUND The role of Blastocystis, a common intestinal parasitic protist of humans and other animals, in human health and disease remains elusive. Recent studies suggest a connection between Blastocystis colonization, healthier lifestyles, and high-diversity gut microbiota. Nevertheless, studies concerning the relationship between Blastocystis colonization, its intensity, and gut microbiota composition -involving both bacterial and eukaryotic communities- remain limited. METHODS This study examines the impact of Blastocystis carriage and colonization intensity on gut microbiota composition in a rural community in Colombia. A total of 88 human samples were collected from the rural population of Las Guacas village, located in the Cauca department in southwest Colombia. We utilized 16S and 18S rDNA sequencing to analyze both bacterial and eukaryotic microbiota, comparing Blastocystis-positive and -negative individuals, as well as groups with varying Blastocystis colonization intensity (low, medium, high), to identify distinct microbiota profiles and differentially abundant taxa linked to each condition. RESULTS The analysis revealed significant differences between Blastocystis-positive and -negative individuals. In terms of bacterial composition and structure, Blastocystis-positive individuals exhibited distinct microbiota profiles, as shown by beta diversity analysis. Taxa associated with colonization included Bacteroides, Prevotella, Oscillibacter, Faecalibacterium, and Alistipes. Higher Blastocystis colonization intensity was associated with an increased abundance of taxa such as Alistipes and Lachnospira, while lower intensities correlated with beneficial bacteria such as Akkermansia. Regarding eukaryotic composition, beta diversity analysis revealed distinct profiles associated with Blastocystis colonization. Differentially abundant taxa, including Entamoeba coli, were more prevalent in Blastocystis-positive individuals, while Blastocystis-negative individuals exhibited a higher abundance of opportunistic fungi, such as Candida albicans. Machine learning models, including random forest classifiers, supported these findings, identifying Faecalibacterium and Bacteroides as predictors of Blastocystis colonization. CONCLUSIONS These findings suggest that Blastocystis may modulate gut microbiota, contributing to microbial balance providing new insights into the ecological implications of Blastocystis in rural populations.
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Affiliation(s)
- Sergio Castañeda
- Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia
| | - Jeff Tomiak
- Laboratory of Parasitology, Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark
- University of Stavanger, Department of Chemistry, Bioscience, and Environmental Engineering, Stavanger, Norway
| | - Lee O'Brien Andersen
- Laboratory of Parasitology, Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark
| | - Claudia Patricia Acosta
- Grupo de investigación en Genética Humana, Departamento de Ciencias Fisiológicas, Facultad de Ciencias de la Salud, Universidad del Cauca
| | - Luis Reinel Vasquez-A
- Centro de Estudios en Microbiología y Parasitología, Facultad de Ciencias de la Salud, Universidad del Cauca, Popayán, Colombia
| | - Christen Rune Stensvold
- Laboratory of Parasitology, Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark
| | - Juan David Ramírez
- Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia
- Molecular Microbiology Laboratory, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York city, New York, United States of America
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11
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Wang D, Lu Q, Liu X, Li Y, Du M, Zhao M, Tong Y, Ni BJ. [P(CH 2OH) 4]Cl induced natural shift of methanogenic pathway through disrupting bacterial disulfide bonds and reshaping microbial community structure. JOURNAL OF HAZARDOUS MATERIALS 2025; 494:138609. [PMID: 40367778 DOI: 10.1016/j.jhazmat.2025.138609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 04/06/2025] [Accepted: 05/12/2025] [Indexed: 05/16/2025]
Abstract
Ionic liquids (ILs), which are expanding produced and applied as alternatives to volatile organic solvents, have shown the ability to deteriorate the anaerobic biotransformation of organics. It is unclear, nevertheless, how ILs affect different functional anaerobes during anaerobic digestion, leaving a knowledge gap in the environmental risks of ILs. Here, we revealed that the differences of Gram-staining bacteria probably were the part drivers of a shift in methanogenic pathway from acetoclastic to hydrogenotrophic methanogenesis in anaerobic microcosms exposed to a typical IL (Tetrakis (hydroxymethyl) phosphonium chloride, [P(CH2OH)4]Cl). The results showed that 0.1-4 mg/L [P(CH2OH)4]Cl respectively decreased methane production rate and carbon-use efficiency by 4.43-43.90 % and 0.52-57.23 % during anaerobic digestion. Microbial community and microscopic examination analysis indicated that most Gram-positive bacteria were more likely to survive in the [P(CH2OH)4]Cl-present environment than Gram-negative bacteria. Mechanistically, [P(CH2OH)4]Cl distorted cell walls of anaerobes, and then perturbed protein homeostasis in the periplasm by breaking disulfide bonds and disrupting disulfide-bond-forming pathways. Moreover, Gram-positive bacteria exhibited a higher tolerance than Gram-negative bacteria, potentially due to their thicker peptidoglycan structures and reliance less on disulfide bonds to stabilize proteins, leading to the remodeling of microbiome function and carbon-transport pathway. This study is the first to reveal the differential impact of [P(CH2OH)4]Cl on Gram-positive vs. Gram-negative anaerobes during methanogenesis, providing new insights into the ecological risks of ILs and contributing to their optimal design.
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Affiliation(s)
- Dongbo Wang
- College of Environmental Science and Engineering and Key Laboratory of Environmental Biology and Pollution Control (Ministry of Education), Hunan University, Changsha 410082, PR China
| | - Qi Lu
- College of Environmental Science and Engineering and Key Laboratory of Environmental Biology and Pollution Control (Ministry of Education), Hunan University, Changsha 410082, PR China
| | - Xuran Liu
- State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, PR China; School of Civil and Environmental Engineering, The University of New South Wales, Sydney, NSW 2052, Australia.
| | - Yingbin Li
- College of Environmental Science and Engineering and Key Laboratory of Environmental Biology and Pollution Control (Ministry of Education), Hunan University, Changsha 410082, PR China
| | - Mingting Du
- College of Environmental Science and Engineering and Key Laboratory of Environmental Biology and Pollution Control (Ministry of Education), Hunan University, Changsha 410082, PR China
| | - Mengxi Zhao
- College of Environmental Science and Engineering and Key Laboratory of Environmental Biology and Pollution Control (Ministry of Education), Hunan University, Changsha 410082, PR China
| | - Yao Tong
- College of Environmental Science and Engineering and Key Laboratory of Environmental Biology and Pollution Control (Ministry of Education), Hunan University, Changsha 410082, PR China
| | - Bing-Jie Ni
- School of Civil and Environmental Engineering, The University of New South Wales, Sydney, NSW 2052, Australia.
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12
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Schnizlein MK, Dubey AA, Fiebig A, Crosson S. Genetic- and culture-based tools for studying Bacteroides fragilis. Microbiol Resour Announc 2025; 14:e0000625. [PMID: 40130927 PMCID: PMC12060699 DOI: 10.1128/mra.00006-25] [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: 01/15/2025] [Accepted: 03/04/2025] [Indexed: 03/26/2025] Open
Abstract
The relatively limited availability of genetic tools has hampered mechanistic studies of Bacteroides fragilis, an opportunistic anaerobe that constitutes 1%-5% of the gut microbiota in healthy humans. Here we describe novel vectors for B. fragilis gene deletion and expression as well as a semi-defined media for cultivation of B. fragilis str. P207.
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Affiliation(s)
- Matthew K. Schnizlein
- Department of Microbiology, Genetics and Immunology, Michigan State University, East Lansing, Michigan, USA
| | - Abhishek A. Dubey
- Leibniz Institute on Aging, Fritz Lipmann Institute, Jena, Thuringia, Germany
| | - Aretha Fiebig
- Department of Microbiology, Genetics and Immunology, Michigan State University, East Lansing, Michigan, USA
| | - Sean Crosson
- Department of Microbiology, Genetics and Immunology, Michigan State University, East Lansing, Michigan, USA
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13
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Delvallez G, Diancourt L, Germond J, Campagne P, Dupuy B. Comparison of Disc Diffusion and Sensititre® Broth Microdilution Methods for Antimicrobial Susceptibility Testing of Bacteroides fragilis Group clinical isolates following the French Guidelines. Anaerobe 2025:102969. [PMID: 40339735 DOI: 10.1016/j.anaerobe.2025.102969] [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: 01/06/2025] [Revised: 04/14/2025] [Accepted: 04/28/2025] [Indexed: 05/10/2025]
Abstract
OBJECTIVES This study aims to evaluate the concordance between the disc diffusion test (DDT) and custom-designed Sensititre® Broth Microdilution plates and to estimate their respective sensitivity (Se) and specificity (Sp) for antimicrobial susceptibility testing (AST) of Bacteroides fragilis group (BFG) clinical isolates. METHODS AST was performed on 126 BFG isolates using both DDT and Sensititre® methods according to the 2024 CA-SFM guidelines. Cohen's kappa coefficients were used to assess concordance, while a Bayesian approach estimated Se and Sp with 95% confidence intervals (95% CIs) for amoxicillin-clavulanate (AMC), piperacillin-tazobactam (PTZ), imipenem (IPM), clindamycin (CLI), metronidazole (MTR), and moxifloxacin (MXF). RESULTS Cohen's kappa coefficients with 95% CIs for AMC, PTZ, IPM, CLI, MTR, and MXF were 0.92 (0.85-1.00), 0.70 (0.56-0.83), 0.96 (0.92-1.00), 0.98 (0.94-1.00), 0.96 (0.89-1.00), and 0.70 (0.58-0.82), respectively. DDT demonstrated Se > 0.8 for all antibiotics, and Sp > 0.8 except for PTZ (0.51; 0.37-0.65) and CLI (0.71; 0.58-0.82). Sensititre® exhibited Se > 0.9 for all antibiotics except for PTZ (0.86; 0.70-0.99), and Sp > 0.9 except for MXF (0.88; 0.75-0.99). CONCLUSIONS DDT and Sensititre® Broth Microdilution demonstrated strong concordance for most antibiotics. Predictive values estimated using Bayesian model showed that Sensititre® offered the highest overall Se and Sp.
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Affiliation(s)
- Gauthier Delvallez
- National Reference Center for Anaerobic bacteria and Botulism, Institut Pasteur, Université Paris Cité, Paris, France; Laboratory Pathogenesis of Bacterial Anaerobes, Institut Pasteur, Université Paris Cité, Paris, France.
| | - Laure Diancourt
- National Reference Center for Anaerobic bacteria and Botulism, Institut Pasteur, Université Paris Cité, Paris, France.
| | - Julie Germond
- National Reference Center for Anaerobic bacteria and Botulism, Institut Pasteur, Université Paris Cité, Paris, France.
| | - Pascal Campagne
- Bioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris Cité, Paris, France.
| | - Bruno Dupuy
- Laboratory Pathogenesis of Bacterial Anaerobes, Institut Pasteur, Université Paris Cité, Paris, France.
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14
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Hjørne AP, Mortensen MS, Licht TR, Laursen MF. Loperamide increases mouse gut transit time in a dose-dependent manner with treatment duration-dependent effects on distinct gut microbial taxa. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2025; 6:e7. [PMID: 40336798 PMCID: PMC12056420 DOI: 10.1017/gmb.2025.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 04/09/2025] [Accepted: 04/10/2025] [Indexed: 05/09/2025]
Abstract
Intestinal transit time has been recognized as an important factor in shaping the gut microbiota, although causality remains to be firmly demonstrated. The aim of this study was to evaluate the effect of different loperamide doses on the mouse intestinal transit time and to investigate the effects of increasing transit time on the gut microbial community. Loperamide significantly increased the transit time in a dose-dependent manner. Additionally, we observed a significant difference between the control group and the loperamide-treated groups in the abundance of the bacterial families Bacteroidaceae, Erysipelotrichaceae, Porphyromonadaceae, and Akkermansiaceae after 7 days of loperamide treatment, with the bacterial families responding to the increased transit time at different rates. Fermentation of faeces obtained from the same mice, with or without loperamide, demonstrated that the observed effects on gut microbiota in vivo were not a result of direct interactions between loperamide and the gut microbiota but rather a consequence of loperamide-induced increased intestinal transit time. In the cecum of the mice, we found higher levels of propionate in the high-dose group compared to the control and low-dose groups. Collectively, our findings establish that an altered transit time is causal to changes in the composition and activity of the microbiome.
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Affiliation(s)
- Anna Pii Hjørne
- National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark
| | | | - Tine Rask Licht
- National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark
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15
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He G, Zhang B, Chen T, Shen C, Wang N, Yang J, Chang F, Sui Y, Yin X, Wang Y, Wang S, Li Y, Zong J, Luo Y, Meng Y, Li C, Zhou X. Effects of chitosan on restoring spermatogenesis in mice: Insights from gut microbiota and multi-omics analysis. Food Res Int 2025; 208:116218. [PMID: 40263850 DOI: 10.1016/j.foodres.2025.116218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 02/10/2025] [Accepted: 03/11/2025] [Indexed: 04/24/2025]
Abstract
Chitosan, is a natural bio-based polymer with known prebiotic properties. However, its potential in the management of spermatogenic disorders remains largely unexplored. By utilizing a busulfan-treated mouse model and integrated multi-omics analysis, this study explored the potential mechanisms through which chitosan improves impaired spermatogenesis. The results showed that chitosan treatment can improve testicular function and significantly reshape the gut microbiota composition in busulfan-treated mice. Metabolomics revealed that docosahexaenoic acid (DHA) transport was significantly dysregulated in busulfan-treated mice, but chitosan reversed this dysfunction by modulating tight junction proteins and fatty acid transporters in the intestine. Fecal microbiota transplantation experiments further highlighted the critical role of gut microbiota in DHA transport and spermatogenesis. Additionally, DHA supplementation alleviated busulfan-induced ferroptosis in testicular tissues. Hence, owing to its prebiotic effects chitosan could serve as a novel therapeutic strategy for improving busulfan-induced spermatogenic disorders by restoring the homeostasis of the gut-testis axis.
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Affiliation(s)
- Guitian He
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Boqi Zhang
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Tong Chen
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Caomeihui Shen
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Nan Wang
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Junjun Yang
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Fuqiang Chang
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Yue Sui
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Xuanqi Yin
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Yueying Wang
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Sihui Wang
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Yaqiu Li
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Jinxin Zong
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Yuxin Luo
- College of Animal Sciences, Jilin University, Changchun, Jilin, China
| | - Yang Meng
- Jilin Province Product Quality Supervision and Inspection Institute, China
| | - Chunjin Li
- College of Animal Sciences, Jilin University, Changchun, Jilin, China.
| | - Xu Zhou
- College of Animal Sciences, Jilin University, Changchun, Jilin, China.
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16
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Dong J, Al‐Issa M, Feeney JS, Shelp GV, Poole EM, Cho CE. Prenatal Intake of High Multivitamins or Folic Acid With or Without Choline Contributes to Gut Microbiota-Associated Dysregulation of Serotonin in Offspring. Mol Nutr Food Res 2025; 69:e70044. [PMID: 40123263 PMCID: PMC12050513 DOI: 10.1002/mnfr.70044] [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: 10/25/2024] [Revised: 02/23/2025] [Accepted: 03/11/2025] [Indexed: 03/25/2025]
Abstract
The gut microbiota is amenable to early nutrition including micronutrients but intake above and below the recommendations commonly occur with unknown consequences. Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine found centrally and peripherally with diverse functions such as food intake regulation via the hypothalamic 5-HT receptor 2C (5-HTR2C). This study determined the impact of prenatal micronutrients on the gut microbiota and serotonergic system in offspring. Pregnant Wistar rats were fed either recommended vitamins (RV), high vitamins (HV), high folic acid with recommended choline (HFRC), or high folic acid with no choline (HFNC). Offspring were fed a high-fat diet for 12 weeks postweaning. HV, HFRC, and HFNC males and females had lower hypothalamic 5-HTR2C protein expression compared to RV. Brain 5-HT concentrations were lower but colon 5-HT concentrations were higher in HV and HFNC males and females and HFRC males compared to RV. Refeeding response after 5-HTR2C agonist was negatively correlated with hypothalamic 5-HTR2C protein expression in males and with brain 5-HT concentrations in females. Random forest revealed top bacterial taxa, which Lactococcus, Ruminococcus, Bacteroides, and Oscillospira showed significant correlations with refeeding response and concentrations of brain and colon 5-HT. In conclusion, excess or imbalanced prenatal consumption of micronutrients leads to gut microbiota-associated disturbances in the serotonergic system in offspring.
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Affiliation(s)
- Jianzhang Dong
- Department of Human Health and Nutritional SciencesUniversity of GuelphGuelphOntarioCanada
| | - Mali Al‐Issa
- Department of Human Health and Nutritional SciencesUniversity of GuelphGuelphOntarioCanada
| | - Jenny S. Feeney
- Department of Human Health and Nutritional SciencesUniversity of GuelphGuelphOntarioCanada
| | - Gia V. Shelp
- Department of Human Health and Nutritional SciencesUniversity of GuelphGuelphOntarioCanada
| | - Elizabeth M. Poole
- Department of Family Relations and Applied NutritionUniversity of GuelphGuelphOntarioCanada
| | - Clara E. Cho
- Department of Human Health and Nutritional SciencesUniversity of GuelphGuelphOntarioCanada
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Zhai S, Peng X, Liu C, Zhang R, Jin C, Jiang X, Feng P, Liang Y, Yuan X, Zhang J, Yang Y. Ginsenoside Rg1 alleviates ochratoxin A-induced liver inflammation in ducklings: Involvement of intestinal microbiota modulation and the TLR4/NF-κB pathway inhibition. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 296:118186. [PMID: 40222107 DOI: 10.1016/j.ecoenv.2025.118186] [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: 01/10/2025] [Revised: 04/03/2025] [Accepted: 04/10/2025] [Indexed: 04/15/2025]
Abstract
Ochratoxin A (OTA) is a toxic fungal secondary metabolite that triggers liver inflammation in animals. OTA could disrupt intestinal microbiota balance by promoting Gram-negative bacteria growth and activating the Toll-like receptor 4 (TLR4)/Nuclear factor-kappa B (NF-κB) signaling pathway, thereby inducing liver inflammation. Ginsenoside Rg1 (Rg1) is an active component of ginseng, exhibits anti-inflammatory, antibacterial, and antioxidative properties, particularly against gram-negative bacteria. Rg1 has been shown to maintain intestinal microbiota homeostasis and inhibit the TLR4 signaling pathway to alleviate liver inflammation. Given these established mechanisms, the aim of this study was to explore the preventive effect of Rg1 in countering OTA-induced liver inflammation through modulation of intestinal microbiota and the TLR4/NF-κB signaling pathway. The results revealed that Rg1 reduced OTA residues in the cecum and enhanced intestinal barrier function. Moreover, Rg1 ameliorated the intestinal microbiota composition in OTA-treated ducklings by decreasing the relative abundance of lipopolysaccharide (LPS)-related bacteria. Rg1 also increases the abundance of short-chain fatty acid (SCFA)-producing bacteria. Additionally, Rg1 supplementation with OTA decreased the accumulation of LPS in tissues and inhibited the TLR4/NF-κB signaling pathway. Intriguingly, Rg1 maintained its beneficial effects in OTA-treated ducklings even after antibiotic treatment by inhibiting the TLR4/NF-κB pathway. These findings emphasized the importance of intestinal microbiota homeostasis and TLR4/NF-κB pathway suppression in the anti-inflammatory action of Rg1 during OTA-induced liver inflammation.
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Affiliation(s)
- Shuangshuang Zhai
- College of Animal Science and Technology, Yangtze University, Jingzhou, Hubei Province 434023, China.
| | - Xin Peng
- College of Animal Science and Technology, Yangtze University, Jingzhou, Hubei Province 434023, China
| | - Cheng Liu
- College of Animal Science and Technology, Yangtze University, Jingzhou, Hubei Province 434023, China
| | - Ran Zhang
- Shenzhen International Travel Health Care Center (Shenzhen Customs District Port Outpatient Clinics), Shenzhen Customs District, Shenzhen 518000, China
| | - Chunlong Jin
- Shenzhen International Travel Health Care Center (Shenzhen Customs District Port Outpatient Clinics), Shenzhen Customs District, Shenzhen 518000, China
| | - Xiayu Jiang
- College of Animal Science and Technology, Yangtze University, Jingzhou, Hubei Province 434023, China
| | - Peishi Feng
- College of Pharmacy, Zhejiang University of Technology, Hangzhou, Zhejiang Province 310014, China
| | - Yuting Liang
- College of Animal Science and Technology, Yangtze University, Jingzhou, Hubei Province 434023, China
| | - Xi Yuan
- College of Animal Science and Technology, Yangtze University, Jingzhou, Hubei Province 434023, China
| | - Jinqiu Zhang
- College of Animal Science and Technology, Yangtze University, Jingzhou, Hubei Province 434023, China
| | - Ye Yang
- College of Animal Science and Technology, Yangtze University, Jingzhou, Hubei Province 434023, China
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18
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Yang X, Zhao Q, Wang X, Zhang Y, Ma J, Liu Y, Wang H. Investigation of Clostridium butyricum on atopic dermatitis based on gut microbiota and TLR4/MyD88/ NF-κB signaling pathway. Technol Health Care 2025; 33:1532-1547. [PMID: 39973880 DOI: 10.1177/09287329241301680] [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: 02/21/2025]
Abstract
BackgroundProbiotics, as common regulators of the gut microbiota, have been used in research to alleviate clinical symptoms of atopic dermatitis (AD).ObjectiveOur research team has previously identified a potential relieving effect of Clostridium butyricum on the treatment of AD, but the specific mechanism of how Clostridium butyricum alleviates AD has not yet been confirmed.MethodsIn this study, we explored the relieving effect of Clostridium butyricum on AD through in vivo and in vitro experiments. AD mice induced by 2,4-dinitrofluorobenzene (DNFB) were orally administered with 1 × 108 CFU of Clostridium butyricum for three consecutive weeks.ResultsOral administration of Clostridium butyricum reduced ear swelling, alleviated back skin lesions, decreased mast cell and inflammatory cell infiltration, and regulated the levels of inflammation-related cytokines. Clostridium butyricum activated the intestinal immune system through the TLR4/MyD88/NF-κB signaling pathway, suppressed the expression of inflammatory factors IL-10 and IL-13, and protected the damaged intestinal mucosa.ConclusionClostridium butyricum administration improved the diversity and abundance of the gut microbiota, enhanced the functionality of the immune system, and protected the epidermal barrier.
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Affiliation(s)
- Xiaojing Yang
- Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, China
| | - Qian Zhao
- Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, China
| | - Xing Wang
- Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, China
| | - Yiming Zhang
- Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, China
| | - Jingyue Ma
- Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, China
| | - Yuanjun Liu
- Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, China
| | - Huiping Wang
- Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, China
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Kongpanna P, Jamikorn U, Tripipat T, Tantituvanont A, Ngampak R, Nilubol D. Efficacy of Three Doses of Halquinol on Growth Performance, Diarrhea Incidence, Nutrient Digestibility, and Fecal Microbiome of Weaned Pigs. Animals (Basel) 2025; 15:1258. [PMID: 40362078 PMCID: PMC12071017 DOI: 10.3390/ani15091258] [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: 03/04/2025] [Revised: 04/18/2025] [Accepted: 04/19/2025] [Indexed: 05/15/2025] Open
Abstract
The weaning period is a critical phase for nursery pigs that is characterized by rapid growth and alterations in the intestinal microbiome associated with nutrient utilization. The present study aimed to investigate the efficacy of halquinol, when used as an antibiotic (ABO), on the growth performance, diarrhea incidence, coefficient of apparent total tract digestibility (CATTD), fecal volatile fatty acids (VFAs), and microbiota in pigs. A total of 210 healthy weaned pigs with an average initial weight of 6.9 kg and aged 28 ± 2 days were assigned to five treatments (six pens/treatment) in a complete randomized design, including a control group (T1, CON; feed with no ABO), a colistin group (T2, CLT; feed containing 120 ppm colistin), and three halquinol groups (T3 to T5, HAL; feed containing 180, 240, and 360 ppm halquinol, respectively). The experiment period lasted for 10 days. Field recordings, observation, and feces collection were performed on D1, D5, and D10. CATTD and VFA assessments were conducted on D10. The composition of the fecal microbiota was analyzed via 16S rRNA gene sequencing using the Illumina Miseq platform. The results demonstrated that the in-feed ABO groups exhibited a significantly lower ADFI (p < 0.01). Pigs fed the T3 and T4 diets had the lowest FCR (p < 0.01) on D5 and D10 and, thus, had reduced ADFI (p < 0.01). A quadratic contrast was found in ADFI and FCR on D5 and D10, indicating a negative correlation with HAL concentration (p < 0.01). Pigs fed CLT and HAL had significantly reduced levels of coliform (p < 0.01) and E. coli (p < 0.01). Moreover, pigs receiving ABO also had a lower fecal score compared to those on the CON diet (p < 0.01). Dietary in-feed ABO had no effect on all the parameters of the CATTD on D10 (p > 0.05), except for fat digestibility in pigs that received T4 (p < 0.01). Pigs fed the T4 and T5 diets had higher propionate concentrations and lower A/P ratios than pigs fed T1, T2, and T3 (p < 0.01). The microbial diversity shifted quickly through the early weaning period. The relative abundance of beneficial Enterococcus microbes increased in pigs fed in-feed ABO, whereas the relative prevalence of pathogenic bacteria, such as Escherichia and Klebsiella, decreased. Escherichia and Bacteroides were negatively correlated with carbohydrate digestibility and butyric and valeric acid production (p < 0.05). Overall, the appropriate HAL dosage was 240 ppm (T4), and this antimicrobial can potentially be characterized as an in-feed colistin replacer that improves feed efficiency and fat digestion, enhancing VFA production, alleviating post-weaning diarrhea, and protecting ABO-resistant piglets.
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Affiliation(s)
- Panumas Kongpanna
- Department of Animal Husbandry, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand; (P.K.); (U.J.)
| | - Uttra Jamikorn
- Department of Animal Husbandry, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand; (P.K.); (U.J.)
| | - Thitima Tripipat
- Swine Viral Evolution and Vaccine Development Research Unit, Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand;
| | - Angkana Tantituvanont
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand;
| | - Rakthai Ngampak
- Department of Livestock Development, Ministry of Agriculture and Cooperatives, Bangkok 10400, Thailand;
| | - Dachrit Nilubol
- Swine Viral Evolution and Vaccine Development Research Unit, Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand;
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20
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Thapa HB, Passegger CA, Fleischhacker D, Kohl P, Chen YC, Kalawong R, Tam-Amersdorfer C, Gerstorfer MR, Strahlhofer J, Schild-Prüfert K, Zechner EL, Blesl A, Binder L, Busslinger GA, Eberl L, Gorkiewicz G, Strobl H, Högenauer C, Schild S. Enrichment of human IgA-coated bacterial vesicles in ulcerative colitis as a driver of inflammation. Nat Commun 2025; 16:3995. [PMID: 40301356 PMCID: PMC12041585 DOI: 10.1038/s41467-025-59354-5] [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: 03/01/2024] [Accepted: 04/21/2025] [Indexed: 05/01/2025] Open
Abstract
The gut microbiome contributes to chronic inflammatory responses in ulcerative colitis (UC), but molecular mechanisms and disease-relevant effectors remain unclear. Here we analyze the pro-inflammatory properties of colonic fluid obtained during colonoscopy from UC and control patients. In patients with UC, we find that the pelletable effector fraction is composed mostly of bacterial extracellular vesicles (BEVs) that exhibit high IgA-levels and incite strong pro-inflammatory responses in IgA receptor-positive (CD89+) immune cells. Biopsy analyses reveal higher infiltration of CD89+ immune cells in the colonic mucosa from patients with UC than control individuals. Further studies show that IgA-coated BEVs, but not host-derived vesicles nor soluble IgA, are potent activators of pro-inflammatory responses in CD89+ cells. IgA-coated BEVs also exacerbate intestinal inflammation in a dextran sodium sulfate colitis model using transgenic mice expressing human CD89. Our data thus implicate a link between IgA-coated BEVs and intestinal inflammation via CD89+ immune cells, and also hint a potential new therapeutic target for UC.
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Affiliation(s)
- Himadri B Thapa
- Institute of Molecular Biosciences, University of Graz, Graz, Austria
| | - Christina A Passegger
- Division of Immunology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria
| | | | - Paul Kohl
- Institute of Molecular Biosciences, University of Graz, Graz, Austria
| | - Yi-Chi Chen
- Department of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland
| | - Ratchara Kalawong
- Department of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland
| | - Carmen Tam-Amersdorfer
- Division of Immunology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria
| | - Michael R Gerstorfer
- Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria
| | - Jana Strahlhofer
- Institute of Molecular Biosciences, University of Graz, Graz, Austria
| | | | - Ellen L Zechner
- Institute of Molecular Biosciences, University of Graz, Graz, Austria
- BioTechMed, Graz, Austria
- Field of Excellence Biohealth - University of Graz, Graz, Austria
| | - Andreas Blesl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Lukas Binder
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Georg A Busslinger
- Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria
| | - Leo Eberl
- Department of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland
| | - Gregor Gorkiewicz
- BioTechMed, Graz, Austria
- Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Herbert Strobl
- Division of Immunology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria
- BioTechMed, Graz, Austria
| | - Christoph Högenauer
- BioTechMed, Graz, Austria.
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
| | - Stefan Schild
- Institute of Molecular Biosciences, University of Graz, Graz, Austria.
- BioTechMed, Graz, Austria.
- Field of Excellence Biohealth - University of Graz, Graz, Austria.
- Austrian Agency for Health and Food Safety (AGES), Institute for Medical Microbiology and Hygiene, Graz, Austria.
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21
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Cresci GA, Liu Q, Sangwan N, Liu D, Grove D, Shapiro D, Ali K, Cazzaniga B, Prete LD, Miller C, Hashimoto K, Quintini C. The Impact of Liver Graft Preservation Method on Longitudinal Gut Microbiome Changes Following Liver Transplant: A Proof-of-concept Study. J Clin Transl Hepatol 2025; 13:284-294. [PMID: 40206278 PMCID: PMC11976440 DOI: 10.14218/jcth.2024.00352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Revised: 01/07/2025] [Accepted: 01/13/2025] [Indexed: 04/11/2025] Open
Abstract
Background and Aims End-stage liver disease is associated with disruptions in gut microbiota composition and function, which may facilitate gut-to-liver bacterial translocation, impacting liver graft integrity and clinical outcomes following liver transplantation. This study aimed to assess the impact of two liver graft preservation methods on fecal microbiota and changes in fecal and breath organic acids following liver transplantation. Methods This single-center, non-randomized prospective pilot study enrolled liver transplant patients whose grafts were preserved using either static cold storage or ex situ normothermic machine perfusion (NMP). Fresh stool and breath samples were collected immediately before surgery and at postoperative months 3, 6, and 12. Stool microbiota was profiled via 16S rRNA gene sequencing, stool short-chain fatty acids were measured using gas chromatography/-mass spectrometry, and breath volatile organic compounds (VOCs) were analyzed with selected-ion flow-tube mass spectrometry. Results Both cohorts experienced a loss of microbiota diversity and dominance by single taxa. The NMP cohort demonstrated enrichment of several beneficial gut taxa, while the static cold storage cohort showed depletion of such taxa. Various gut bacteria were found to correlate with stool short-chain fatty acids (e.g., lactic acid, butyric acid) and several VOCs. Conclusions Fecal microbiota alterations associated with end-stage liver disease do not fully normalize to a healthy control profile following liver transplantation. However, notable differences in microbiota composition and function were observed between liver graft preservation methods. Future research with larger randomized cohorts is needed to explore whether the NMP-associated shift in gut microbiota impacts clinical outcomes and if breath VOCs could serve as biomarkers of the clinical trajectory in liver transplant patients.
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Affiliation(s)
- Gail A.M. Cresci
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland, OH, USA
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
- Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Qiang Liu
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
- Transplant Center, Cleveland Clinic, Cleveland, OH, USA
| | - Naseer Sangwan
- Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
- Cardiovascular and Metabolic Sciences/Shared Laboratory Resources, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Darren Liu
- Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - David Grove
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - David Shapiro
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Khaled Ali
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
- Transplant Center, Cleveland Clinic, Cleveland, OH, USA
| | - Beatrice Cazzaniga
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
- Transplant Center, Cleveland Clinic, Cleveland, OH, USA
| | - Luca Del Prete
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
- Transplant Center, Cleveland Clinic, Cleveland, OH, USA
| | - Charles Miller
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
- Transplant Center, Cleveland Clinic, Cleveland, OH, USA
| | - Koji Hashimoto
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
- Transplant Center, Cleveland Clinic, Cleveland, OH, USA
| | - Cristiano Quintini
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates
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22
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Häsler R, Mikš MH, Bajic D, Soyyilmaz B, Bendik I, van Buul VJ, Steinert RE, Rehman A. Human Milk Oligosaccharides Modulating Inflammation in Infants, Adults, and Older Individuals-From Concepts to Applications. Adv Nutr 2025:100433. [PMID: 40287068 DOI: 10.1016/j.advnut.2025.100433] [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: 09/16/2024] [Revised: 04/17/2025] [Accepted: 04/18/2025] [Indexed: 04/29/2025] Open
Abstract
The increasing global prevalence of inflammatory diseases, such as ulcerative colitis and irritable bowel syndrome, represents a challenging task for healthcare systems. Several approaches to disease management target the intestinal microbiome, which plays a key role in health and disease. One promising approach is modulating the microbiome using human milk oligosaccharides (HMOs). Originating from human milk, HMOs are indigestible carbohydrates that act in a host-optimized prebiotic fashion by providing an energy source for health-promoting intestinal bacteria and exhibiting systemic effects. Commercial products supporting infant health and development have been the primary fields of HMO application. Advancements in the large-scale production of HMOs through bioengineering and precision fermentation have led to evaluation of their potential for managing inflammatory diseases. Several in vitro studies and observations on model systems have been clinically validated in infants, resulting in a large body of evidence supporting the safety and efficacy of HMOs in inflammatory disorders. Although novel approaches seek to explore interventions in adults, the primary goal for the future is to provide cost-efficient, safe, and reliable healthcare compounds across all age groups.
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Affiliation(s)
- Robert Häsler
- Department of Dermatology and Allergology, University Kiel, Kiel, Germany.
| | - Marta Hanna Mikš
- Faculty of Food Science, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland; DSM-firmenich, Hørsholm, Denmark
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23
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Khan I, Khan I, Xie P, Xiaohui Y, Lei S, Song T, Li Z, Xie X. Insights into the blood, gut, and oral microbiomes in Chinese patients with myocardial infarction: a case-control study. BMC Microbiol 2025; 25:226. [PMID: 40253360 PMCID: PMC12008866 DOI: 10.1186/s12866-025-03878-9] [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: 10/29/2024] [Accepted: 03/10/2025] [Indexed: 04/21/2025] Open
Abstract
BACKGROUND Emerging evidence suggests that changes in the blood microbes might be associated with cardiovascular disease, especially myocardial infarction (MI). However, some researchers are questioning whether a true "blood microbiome" actually exists. They hypothesized that these microbes may translocate into the bloodstream from the gut or oral cavities. To test this hypothesis, we analyzed the microbial composition, diversity, and potential role in disease progression by comparing blood, gut, and oral microbiota profiles in a cohort of MI patients and healthy controls. METHODS In this study, 144 samples, including blood, fecal, and saliva, were collected from twenty-four myocardial infarction patients and twenty-four healthy controls. These samples were analyzed using 16 S rRNA sequencing to characterize the microbial profiles across the three distinct microbial compartments. Differential analyses were conducted to find key differential microbiota for MI. Spearman's rank correlation analysis was used to study the association between microbiota and clinical indicators. RESULTS Our findings revealed striking microbial shifts across blood, gut, and oral compartments in MI patients compared to healthy controls. In the blood, we observed significant enrichment of the phyla Armatimonadota and Caldatribacteriota, alongside the genera Bacillus, Pedobacter, and Odoribacter. The gut microbiota of MI patients showed a notable increase in the phyla Proteobacteria, Verrucomicrobiota, Cyanobacteria, Synergistota, and Crenarchaeota, as well as the genera Eubacterium_coprostanoligenes_group, Rothia, Akkermansia, Lachnospiraceae_ NK4A136_ group, and Eubacterium_ruminantium_group. Meanwhile, the oral microbiota of MI patients was uniquely enriched with the phylum Elusimicrobiota and the genera Streptococcus, Rothia, and Granulicatella. These distinct microbial signatures highlight compartment-specific alterations that may play a role in the pathophysiology of MI. Additionally, LEfSe analysis identified 64 distinct taxa that differed across the three compartments. Of these, eight taxa were unique to blood, eighteen to the gut, and thirty-eight to the oral microbiota, all of which demonstrated significant associations with clinical markers of MI. Functional pathways were predicted and analyzed via KEGG annotation, but no statistically significant differences were found between MI patients and healthy controls in any of the microbiome compartments. CONCLUSION This study demonstrates significant alterations in the blood, gut, and oral microbiome profiles of MI patients, identifying specific bacterial taxa strongly associated with key markers of myocardial infarction. The unique microbial patterns detected in the blood provide compelling evidence for the existence of a stable core blood microbiome, highlighting its importance as a key contributor to cardiovascular health and disease progression.
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Affiliation(s)
- Ikram Khan
- Department of Genetics, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, 730000, China
| | - Imran Khan
- Department of Microecology, School of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China
| | - Ping Xie
- Department of Cardiology, Gansu Province People's Hospital, Lanzhou, Gansu, China
| | - Yu Xiaohui
- Department of Gastroenterology, The 940 Hospital Joint Logistic Support Force of PLA, Lanzhou, Gansu, China
| | - Shengnan Lei
- School of Stomatology, Key Laboratory of Oral Disease, Northwest Minzu University, Lanzhou, Gansu, China
| | - Tianzhu Song
- School of Stomatology, Key Laboratory of Oral Disease, Northwest Minzu University, Lanzhou, Gansu, China
| | - Zhiqiang Li
- School of Stomatology, Key Laboratory of Oral Disease, Northwest Minzu University, Lanzhou, Gansu, China.
| | - Xiaodong Xie
- Department of Genetics, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, 730000, China.
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24
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Song N, Xu X, Liu P, Jiang Y, Tang X, Zuo D, Lai Z, Cheng J. Integrative analysis of microbiota and metabolomics in individuals exhibiting different TCM constitutions utilizing 16S rDNA sequencing and LC/MS metabolomics. Microb Pathog 2025; 205:107621. [PMID: 40258500 DOI: 10.1016/j.micpath.2025.107621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 11/27/2024] [Accepted: 04/18/2025] [Indexed: 04/23/2025]
Abstract
BACKGROUND Traditional Chinese Medicine (TCM) theory posits a close relationship between an individual's constitutional types and the overall health. Variations in metabolic processes and microbial composition have been observed across different constitution types. This study aims to explore the relationship between TCM constitutions, intestinal flora, and metabolites to devise personalized TCM treatment strategies, enhancing evidence-based guidance for clinical practice. METHODS The research investigated differences in microbial diversity and composition among three TCM constitution types: yin-deficiency constitution (PA), balanced constitution (PH), and yang-deficiency constitution (PI). A significant elevation of the Chao1 metric was noted in the PH group compared to the PI group. RESULTS PCoA and CPCoA analyses demonstrated distinct group separation based on floral samples. Dominant phyla included Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria, with varying abundance at the genus level. Metabolic pathway analysis unveiled disparities in metabolites associated with different pathways among constitution groups. KEGG pathway enrichment analysis emphasized pathways such as steroid hormone biosynthesis, ovarian steroidogenesis, and tryptophan metabolism. Furthermore, correlation analysis revealed associations between specific bacterial taxa and metabolites. CONCLUSION This study delineated the variations in intestinal flora and metabolic profiles among individuals with PA, PH, and PI constitution types, providing valuable insights for the development of personalized TCM treatment approaches.
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Affiliation(s)
- Na Song
- Department of Oncology, Chongqing Traditional Chinese Medicine Hospital, 400021, Chongqing, China
| | - Xinyi Xu
- Department of Oncology, Chongqing Traditional Chinese Medicine Hospital, 400021, Chongqing, China; Hunan University of Chinese Medicine, 410208, Hunan, China
| | - Pingyu Liu
- Department of Oncology, Chongqing Traditional Chinese Medicine Hospital, 400021, Chongqing, China; Hunan University of Chinese Medicine, 410208, Hunan, China
| | - Yutong Jiang
- Physical Examination Center, Chongqing Traditional Chinese Medicine Hospital, 400021, Chongqing, China
| | - Xiaohui Tang
- Department of Oncology, Chongqing Traditional Chinese Medicine Hospital, 400021, Chongqing, China
| | - Deyu Zuo
- Department of Rehabilitation Medicine, Chongqing Traditional Chinese Medicine Hospital, 400021, Chongqing, China; Chongqing Precision Medical Industry Technology Research Institute, Chongqing, 400000, China.
| | - Zonglang Lai
- Department of Oncology, Chongqing Traditional Chinese Medicine Hospital, 400021, Chongqing, China.
| | - Jun Cheng
- Department of Oncology, Chongqing Traditional Chinese Medicine Hospital, 400021, Chongqing, China; Shapingba District Hospital of TCM, Chongqing, 400030, China.
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25
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Dadi P, Pauling CW, Shrivastava A, Shah DD. Synthesis of versatile neuromodulatory molecules by a gut microbial glutamate decarboxylase. iScience 2025; 28:112289. [PMID: 40264799 PMCID: PMC12013497 DOI: 10.1016/j.isci.2025.112289] [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: 10/23/2024] [Revised: 01/14/2025] [Accepted: 03/21/2025] [Indexed: 04/24/2025] Open
Abstract
Dysbiosis of the microbiome correlates with many neurological disorders, yet very little is known about the chemistry that controls the production of neuromodulatory molecules by gut microbes. Here, we found that an enzyme glutamate decarboxylase (BfGAD) of a gut microbe Bacteroides fragilis forms multiple neuromodulatory molecules such as γ-aminobutyric acid (GABA), hypotaurine, taurine, homotaurine, and β-alanine. We evolved BfGAD and doubled its taurine productivity. Additionally, we increased its specificity toward the substrate L-glutamate. Here, we provide a chemical strategy via which the BfGAD activity could be fine-tuned. In future, this strategy could be used to modulate the production of neuromodulatory molecules by gut microbes.
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Affiliation(s)
- Pavani Dadi
- Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ 85281, USA
- School of Life Sciences, Arizona State University, Tempe, AZ 85281, USA
| | - Clint W. Pauling
- Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ 85281, USA
- School of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA
| | - Abhishek Shrivastava
- Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ 85281, USA
- School of Life Sciences, Arizona State University, Tempe, AZ 85281, USA
| | - Dhara D. Shah
- Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ 85281, USA
- School of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA
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26
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Umar S, Yu W, Xuan H, Ahmed I, Zhong C, Morowitz M, Rogers MB, Attard MI, Sampath V. Neonatal gut microbiota succession in mice mapped over time, site, injury and single immunoglobulin interleukin-1 related receptor genotype. iScience 2025; 28:112243. [PMID: 40248118 PMCID: PMC12005339 DOI: 10.1016/j.isci.2025.112243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 01/23/2025] [Accepted: 03/13/2025] [Indexed: 04/19/2025] Open
Abstract
Microbial succession during postnatal gut development in mice is likely impacted by site of sampling, time, intestinal injury, and host genetics. We investigated this in wild-type and Sigirr transgenic mice that encode the p.Y168X mutation identified in a neonate with necrotizing enterocolitis (NEC). Temporal profiling of the ileal and colonic microbiome after birth to weaning revealed a clear pattern of progression from a less diverse, Proteobacteria/Escherichia_Shigella dominant community to a more diverse, Firmicutes/Bacteroidetes dominant community. Formula milk feeding, a risk factor for necrotizing enterocolitis, decreased Firmicutes and increased Proteobacteria leading to enrichment of bacterial genes denoting exaggerated glycolysis and increased production of acetate and lactate. Sigirr transgenic mice exhibited modest baseline differences in microbiota composition but exaggerated formula feeding-induced dysbiosis, mucosal inflammation, and villus injury. Postnatal intestinal microbiota succession in mice resembles human neonates and is shaped by developmental maturity, ileal vs. colonic sampling, formula feeding, and Sigirr genotype.
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Affiliation(s)
- Shahid Umar
- Department of Surgery, University of Kansas Medical Center, USA
| | - Wei Yu
- Department of Pediatrics/Neonatology, Children’s Mercy Hospital, Kansas City, USA
| | - Hao Xuan
- Department of Electrical Engineering and Computer Science, University of Kansas, USA
| | - Ishfaq Ahmed
- Department of Math, Science and Computer Technology, Kansas City Community College, USA
| | - Cuncong Zhong
- Department of Electrical Engineering and Computer Science, University of Kansas, USA
| | - Michael Morowitz
- Division of Pediatric General and Thoracic Surgery, University of Pittsburgh Children’s Hospital, Pittsburgh, PA, USA
| | - Mathew Brian Rogers
- Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Canada
| | - Mark Ivan Attard
- Neonatal Unit, Aberdeen Maternity Hospital, Aberdeen AB25 2ZL, UK
| | - Venkatesh Sampath
- Department of Electrical Engineering and Computer Science, University of Kansas, USA
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27
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Gruninger RJ, McCormack ML, Chomistek NC, Zaheer R, McAllister TA. Unraveling the microbial diversity of bovine liver abscesses: isolation, identification, and genomic characterization of the Bacteroides found in hepatic lesions. Microbiol Spectr 2025:e0042325. [PMID: 40243342 DOI: 10.1128/spectrum.00423-25] [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: 02/27/2025] [Accepted: 03/21/2025] [Indexed: 04/18/2025] Open
Abstract
Liver abscesses in cattle reduce animal performance, increase the environmental footprint of beef production, and cause significant economic losses. The low pH of the rumen resulting from the consumption of high grain diets damages the rumen epithelium and facilitates the translocation of opportunistic pathogens from the gastrointestinal tract into the bloodstream where they can colonize the liver, causing infection. Recently, 16s rRNA sequencing has revealed that 25%-50% of liver abscess microbiomes have prominent levels of Bacteroides. Due to the inability to reliably classify amplicon sequences beyond the genus level, the identity of these microbes remains unknown. We have employed a combination of culture-independent and culture-based methods to isolate and identify the Bacteroides associated with liver abscesses in cattle. Shotgun metagenomic sequencing and assembly of metagenome-assembled genomes generated four high-quality genomes, two of which were putatively identified as Bacteroides. These microbes were subsequently isolated from the purulent material of liver abscesses. Whole-genome sequencing conclusively identified these isolates as Bacteroides pyogenes and a previously unknown species of Bacteroides, revealing distinct differences from Bacteroides typically found in the gut. Carbohydrate utilization assays revealed that both organisms metabolize glycogen and glycosaminoglycans found in the extracellular matrix of the liver but display differences in substrate specificity. These data not only identify Bacteroides found in bovine liver abscesses but also provide new insights into the potential role that these organisms may play in this production-limiting disease. IMPORTANCE Liver abscesses (LAs) are commonly found in cattle raised in feedlots and result from a bacterial infection of the liver. Not only are LAs a concern for animal health, but they also impact growth efficiency, animal welfare, and cost the North American beef industry upwards of $120 million per annum. Recently, it has been found that 25%-50% of liver abscess microbiomes have prominent levels of Bacteroides; however, to date, the biological relevance in LA pathogenesis and the identity of these bacteria are unknown. This research describes the isolation, identification, and genomic characterization of the Bacteroides found in bovine liver abscesses. These data provide a critical foundation for expanding our knowledge of the potential role Bacteroides play in liver abscess development and could contribute to the identification of novel targets for developing treatments to prevent this important production-limiting disease.
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Affiliation(s)
- R J Gruninger
- Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, Alberta, Canada
| | - M L McCormack
- Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, Alberta, Canada
| | - N C Chomistek
- Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, Alberta, Canada
| | - R Zaheer
- Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, Alberta, Canada
| | - T A McAllister
- Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, Alberta, Canada
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Li D, Xue L, Yang H, Yu X. Power-enhanced two-sample mean tests for high-dimensional microbiome compositional data. Biometrics 2025; 81:ujaf034. [PMID: 40171801 PMCID: PMC11962435 DOI: 10.1093/biomtc/ujaf034] [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: 05/10/2024] [Revised: 01/02/2025] [Accepted: 03/07/2025] [Indexed: 04/04/2025]
Abstract
Testing differences in mean vectors is a fundamental task in the analysis of high-dimensional microbiome compositional data. Existing methods may suffer from low power if the underlying signal pattern is in a situation that does not favor the deployed test. In this work, we develop 2-sample power-enhanced mean tests for high-dimensional compositional data based on the combination of $P$-values, which integrates strengths from 2 popular types of tests: the maximum-type test and the quadratic-type test. We provide rigorous theoretical guarantees on the proposed tests, showing accurate Type-I error rate control and enhanced testing power. Our method boosts the testing power toward a broader alternative space, which yields robust performance across a wide range of signal pattern settings. Our methodology and theory also contribute to the literature on power enhancement and Gaussian approximation for high-dimensional hypothesis testing. We demonstrate the performance of our method on both simulated data and real-world microbiome data, showing that our proposed approach improves the testing power substantially compared to existing methods.
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Affiliation(s)
- Danning Li
- KLAS and School of Mathematics & Statistics, Northeast Normal University, Changchun, Jilin 130024, China
| | - Lingzhou Xue
- Department of Statistics, The Pennsylvania State University, University Park, PA 16802, USA
| | - Haoyi Yang
- Department of Statistics, The Pennsylvania State University, University Park, PA 16802, USA
| | - Xiufan Yu
- Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA
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Arslan NP, Azad F, Orak T, Budak-Savas A, Ortucu S, Dawar P, Baltaci MO, Ozkan H, Esim N, Taskin M. A review on bacteria-derived antioxidant metabolites: their production, purification, characterization, potential applications, and limitations. Arch Pharm Res 2025; 48:253-292. [PMID: 40208553 PMCID: PMC12058845 DOI: 10.1007/s12272-025-01541-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 04/02/2025] [Indexed: 04/11/2025]
Abstract
Antioxidants are organic molecules that scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS), thereby maintaining cellular redox balance in living organisms. The human body synthesizes endogenous antioxidants, whereas humans obtain exogenous antioxidants from other organisms such as plants, animals, fungi, and bacteria. This review primarily focuses on the antioxidant potential of natural metabolites and extracts from five major bacterial phyla, including the well-studied Actinobacteria and Cyanobacteria, as well as less-studied Bacteroides, Firmicutes, and Proteobacteria. The literature survey revealed that the metabolites and the extracts with antioxidant activity can be obtained from bacterial cells and their culture supernatants. The metabolites with antioxidant activity include pigments, phycobiliproteins, polysaccharides, mycosporins-like amino acids, peptides, phenolic compounds, and alkaloids. Both metabolites and extracts demonstrate in vitro antioxidant capacity through radical-scavenging, metal-reducing, and metal-chelating activity assays. In in vivo models, they can scavenge ROS and RNS directly and/or indirectly eliminate them by enhancing the activities of antioxidant enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase. Due to their antioxidant activities, they may find applications in the cosmetic industry as anti-aging agents for the skin and in medicine as drugs or supplements for combating oxidative stress-related disorders, such as neurodegenerative diseases and diabetes. The literature survey also elucidated that some metabolites and extracts with antioxidant activity also exhibited strong antimicrobial properties. Therefore, we consider that they may have future applications in the treatment of infectious diseases, the preparation of pathogen-free healthy foods, and the extension of food shelf life.
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Affiliation(s)
| | - Fakhrul Azad
- Department of Biochemistry and Cell Biology, Chobanian and Avedisian School of Medicine, Boston University, Boston, MA, USA
| | - Tugba Orak
- Department of Molecular Biology and Genetics, Science Faculty, Ataturk University, 25240, Erzurum, Turkey
| | - Aysenur Budak-Savas
- Department of Medical Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | - Serkan Ortucu
- Department of Molecular Biology and Genetics, Science Faculty, Erzurum Technical University, Erzurum, Turkey
| | - Pranav Dawar
- Environmental Molecular Sciences Laboratory (EMSL), Pacific Northwest National Laboratory (PNNL), Richland, WA, USA
| | - Mustafa Ozkan Baltaci
- Department of Molecular Biology and Genetics, Science Faculty, Ataturk University, 25240, Erzurum, Turkey
| | - Hakan Ozkan
- Department of Molecular Biology and Genetics, Science Faculty, Ataturk University, 25240, Erzurum, Turkey
| | - Nevzat Esim
- Department of Molecular Biology and Genetics, Science and Art Faculty, Bingol University, Bingol, Turkey
| | - Mesut Taskin
- Department of Molecular Biology and Genetics, Science Faculty, Ataturk University, 25240, Erzurum, Turkey.
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Kato H, Hagihara M, Asai N, Mikamo H, Iwamoto T. A retrospective study comparing the effectiveness of carbapenems and tazobactam/piperacillin as an empirical treatment for patients infected with Bacteroides fragilis. Anaerobe 2025; 92:102950. [PMID: 40032195 DOI: 10.1016/j.anaerobe.2025.102950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 01/28/2025] [Accepted: 02/28/2025] [Indexed: 03/05/2025]
Abstract
BACKGROUND Bacteroides fragilis is one of the most frequently isolated pathogenic anaerobic bacteria. Infections caused by B. fragilis are commonly treated with carbapenems or tazobactam/piperacillin. However, there is no evidence for the optimal antibiotic choice against infections caused by B. fragilis as an empirical therapy owing to its varied antibiotic resistance mechanisms. Hence, we compared the effectiveness of carbapenems and tazobactam/piperacillin as an antibiotic therapy in patients infected with B. fragilis. METHODS We investigated mortality, clinical and antimicrobial efficacy, and the percentage of patients who switched to broad-spectrum antibiotics, such as carbapenems or tazobactam/piperacillin, due to the aggravated symptoms of infection in patients receiving carbapenems or tazobactam/piperacillin from 2019 to 2024. RESULTS A total of 60 patients were included in the study; 24 patients received carbapenems and 36 received tazobactam-piperacillin as an empirical treatment against B. fragilis infections. None of the patients in either group died. Compared to carbapenem treatment, tazobactam/piperacillin treatment significantly improved inflammatory markers, including body temperature and C-reactive protein (45.8 % vs. 72.2 %, p = 0.039 and 37.5 % vs. 63.4 %, p = 0.045, respectively; carbapenem vs. tazobactam/piperacillin). The percentage of patients switching from carbapenems to tazobactam/piperacillin or vice versa was significantly lower in the tazobactam/piperacillin group than in the carbapenem group (41.7 % vs. 11.1 %, p < 0.001). CONCLUSIONS Our findings suggest that tazobactam/piperacillin can be used as the first-line empirical treatment for patients infected with B. fragilis.
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Affiliation(s)
- Hideo Kato
- Department of Pharmacy, Mie University Hospital, Mie, Japan; Department of Clinical Pharmaceutics, Division of Clinical Medical Science, Mie University Graduate School of Medicine, Mie, Japan; Department of Clinical Infectious Diseases, Aichi Medical University, Aichi, Japan.
| | - Mao Hagihara
- Department of Clinical Infectious Diseases, Aichi Medical University, Aichi, Japan; Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University Hospital, Aichi, Japan
| | - Nobuhiro Asai
- Department of Clinical Infectious Diseases, Aichi Medical University, Aichi, Japan
| | - Hiroshige Mikamo
- Department of Clinical Infectious Diseases, Aichi Medical University, Aichi, Japan
| | - Takuya Iwamoto
- Department of Pharmacy, Mie University Hospital, Mie, Japan; Department of Clinical Pharmaceutics, Division of Clinical Medical Science, Mie University Graduate School of Medicine, Mie, Japan
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Alonso-Vásquez T, Fagorzi C, Mengoni A, Oliva M, Cavalieri D, Pretti C, Cangioli L, Bacci G, Ugolini A. Metagenomic surveys show a widespread diffusion of antibiotic resistance genes in a transect from urbanized to marine protected area. MARINE POLLUTION BULLETIN 2025; 213:117640. [PMID: 39908950 DOI: 10.1016/j.marpolbul.2025.117640] [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: 05/24/2024] [Revised: 01/31/2025] [Accepted: 02/01/2025] [Indexed: 02/07/2025]
Abstract
Ports are hot spots of pollution; they receive pollution from land-based sources, marine traffic and port infrastructures. Marine ecosystems of nearby areas can be strongly affected by pollution from port-related activities. Here, we investigated the microbiomes present in sea floor sediments along a transect from the harbour of Livorno (Central Italy) to a nearby marine protected area. Results of 16S rRNA amplicon sequencing and metagenome assembled genomes (MAGs) analyses indicated the presence of different trends of specific bacterial groups (e.g. phyla NB1-j, Acidobacteriota and Desulfobulbales) along the transect, correlating with the measured pollution levels. Human pathogenic bacteria and antibiotic resistance genes (ARGs) were also found. These results demonstrate a pervasive impact of human port activities and highlight the importance of microbiological surveillance of marine sediments, which may constitute a reservoir of ARGs and pathogenic bacteria.
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Affiliation(s)
- Tania Alonso-Vásquez
- Department of Biology, University of Florence, Sesto Fiorentino, 50019 Florence, Italy
| | - Camilla Fagorzi
- Department of Biology, University of Florence, Sesto Fiorentino, 50019 Florence, Italy
| | - Alessio Mengoni
- Department of Biology, University of Florence, Sesto Fiorentino, 50019 Florence, Italy
| | - Matteo Oliva
- Interuniversity Center of Marine Biology and Applied Ecology (CIBM) "G. Bacci", Livorno, Italy
| | - Duccio Cavalieri
- Department of Biology, University of Florence, Sesto Fiorentino, 50019 Florence, Italy
| | - Carlo Pretti
- Interuniversity Center of Marine Biology and Applied Ecology (CIBM) "G. Bacci", Livorno, Italy; Department of Veterinary Science, University of Pisa, San Piero a Grado, Pisa, Italy
| | - Lisa Cangioli
- Department of Biology, University of Florence, Sesto Fiorentino, 50019 Florence, Italy
| | - Giovanni Bacci
- Department of Biology, University of Florence, Sesto Fiorentino, 50019 Florence, Italy.
| | - Alberto Ugolini
- Department of Biology, University of Florence, Sesto Fiorentino, 50019 Florence, Italy
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Jiang B, Wang Z, Wang M, Wang S, Li M, Meng Z, Yuan J, Ke Y. Safety Assessment of Two Human Fecal Bacteroides Strain Isolates in Immunodeficient Mice. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10529-y. [PMID: 40167961 DOI: 10.1007/s12602-025-10529-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2025] [Indexed: 04/02/2025]
Abstract
Bacteroides are potential candidates for next-generation probiotics (NGPs), which require preclinical safety and efficacy evaluations to ensure their rational use. This study aimed to verify the safety of two Bacteroides strains isolated from human fecal samples, Bacteroides dorei CK16 (B. dorei CK16) and Bacteroides vulgatus CK29 (B. vulgatus CK29), using genomic analysis and in vivo experiments. Whole-genome sequencing analysis of B. dorei CK16 revealed a predicted 4,898 protein-coding sequences (CDS), about 5.5 Mb of total genome length with a G + C content of 42.08%, and B. vulgatus CK29 revealed a predicted 4,610 CDS, about 5.3 Mb of total genome length with a G + C content of 42.56%. Moreover, the genome demonstrated the absence of virulence factors, and insertion sequences related to clinically relevant strains in either strain. A 42-day in vivo experiment was conducted on BALB/c and BALB/c nude mice, with each mouse receiving a daily dose of 1 × 108 colony forming units (CFU) /mL of B. dorei CK16 or B. vulgatus CK29. No significant in vivo pathogenic characteristics were observed based on body weight, organ index, hematological, serum biochemical, or histological analyses, particularly in nude mice. Therefore, the initial safety assessment of the two novel Bacteroides strains exhibited no notable adverse effects in both immunocompetent and immunodeficient mice models.
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Affiliation(s)
- Boyi Jiang
- Department of Bacteriology, Capital Institute of Pediatrics, Beijing, 100020, China
- Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100020, China
| | - Zhen Wang
- Department of Bacteriology, Capital Institute of Pediatrics, Beijing, 100020, China
| | - Mingxuan Wang
- Department of Bacteriology, Capital Institute of Pediatrics, Beijing, 100020, China
- College of Food Science and Biology, Hebei University of Science and Technology, Shijiazhuang, 050091, Hebei Province, China
| | - Shijie Wang
- College of Food Science and Biology, Hebei University of Science and Technology, Shijiazhuang, 050091, Hebei Province, China
| | - Mengmeng Li
- Department of Anesthesiology, Fourth Center of Chinese PLA General Hospital, Beijing, 100143, China.
| | - Zhaoting Meng
- Department of Thoracic Medical Oncology, Lung Cancer Diagnosis and Treatment Center, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China.
| | - Jing Yuan
- Department of Bacteriology, Capital Institute of Pediatrics, Beijing, 100020, China.
- Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100020, China.
| | - Yuehua Ke
- Department of Bacteriology, Capital Institute of Pediatrics, Beijing, 100020, China.
- Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100020, China.
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Ji Y, Sun H, Wang Y, Li Y, Piao R, Bu L, Xu H. Characterizing the oral and gastrointestinal microbiome associated with healthy aging: insights from long-lived populations in Northeastern China. GeroScience 2025; 47:2275-2292. [PMID: 39505797 PMCID: PMC11978580 DOI: 10.1007/s11357-024-01419-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 10/29/2024] [Indexed: 11/08/2024] Open
Abstract
The oral and gastrointestinal (GI) tract microbiota in humans is susceptible to geographical influences and represents vital factors impacting healthy aging. The northeastern region of China, characterized by distinct dietary and climatic conditions, significantly influences the human microbiome composition. However, the microbial structure of the entire long-lived population in this area has not been evaluated. This study recruited a cohort of 142 individuals aged 55-102 residing in Northeast China, and their oral and gut microbiota were evaluated using full-length 16S rRNA gene amplicon sequencing. The results indicate that the oral and GI tract microbiota of long-lived individuals showed reduced microbial taxonomic richness and evenness compared to sub-longevity individuals. With aging, the core species experience a gradual decline in abundance, while subordinate species show an increase. The long-lived population exhibited a heightened ability to enrich beneficial bacteria including Akkermansia, Alistipes, Parabacteroides, and Eubacterium coprostanoligenes in the GI tract, which are associated with host metabolism and have the potential to act as probiotics, reducing the risks of unhealthy aging in the northeast population. Bifidobacterium sp. and Lactobacillus salivarius have been found to coexist in both the oral cavity and the GI tract of long-lived individuals. We hypothesize that beneficial bacterial taxa from the oral cavity colonize the GI tract more extensively in long-lived individuals compared to those with a shorter lifespan. These findings pave the way for identifying probiotic strains that can promote healthy aging in Northeast China.
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Affiliation(s)
- Yue Ji
- Jinqiu Hospital of Liaoning Province, Shenyang, 110016, China
| | - Hao Sun
- CAS Key Laboratory of Forest Ecology and Management, Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, 110016, China.
- University of Chinese Academy of Sciences, Beijing, 100049, China.
| | - Yingda Wang
- Jinqiu Hospital of Liaoning Province, Shenyang, 110016, China
| | - Yanhui Li
- Jinqiu Hospital of Liaoning Province, Shenyang, 110016, China
| | - Rennv Piao
- Jinqiu Hospital of Liaoning Province, Shenyang, 110016, China
| | - Li Bu
- Jinqiu Hospital of Liaoning Province, Shenyang, 110016, China.
| | - Hui Xu
- CAS Key Laboratory of Forest Ecology and Management, Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, 110016, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
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Aleksandrova RR, Nieuwenhuis LM, Karmi N, Zhang S, Swarte JC, Björk JR, Gacesa R, Blokzijl H, Connelly MA, Weersma RK, Lisman T, Festen EAM, de Meijer VE. Gut microbiome dysbiosis is not associated with portal vein thrombosis in patients with end-stage liver disease: a cross-sectional study. J Thromb Haemost 2025; 23:1407-1415. [PMID: 39798925 DOI: 10.1016/j.jtha.2024.12.036] [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: 10/08/2024] [Revised: 12/18/2024] [Accepted: 12/23/2024] [Indexed: 01/15/2025]
Abstract
BACKGROUND Portal vein thrombosis (PVT) is a common complication in patients with end-stage liver disease (ESLD). The portal vein in patients with ESLD is proposedly an inflammatory vascular bed due to translocation of endotoxins and cytokines from the gut. We hypothesized that a proinflammatory gut microbiome and elevated trimethylamine N-oxide (TMAO), a driver of thrombosis, may contribute to PVT development. OBJECTIVES We investigated whether gut microbiome diversity, bacterial species, metabolic pathways, and TMAO levels are associated with PVT in patients with ESLD. METHODS Fecal samples, plasma samples, and data from patients with ESLD and healthy controls were collected through the TransplantLines Biobank and Cohort Study. PVT was defined as a thrombus in the portal vein within a year prior to or after fecal sample collection. Fecal samples were analyzed using Shotgun Metagenomic Sequencing, and TMAO levels were measured in plasma using a Vantera Clinical Analyzer. RESULTS One hundred two patients with ESLD, of which 23 with PVT, and 246 healthy controls were included. No significant difference in gut microbiome diversity was found between patients with PVT and without PVT (P = .18). Both ESLD groups had significantly lower alpha diversity than controls. Bacteroides fragilis and 3 Clostridiales species were increased in patients with PVT compared with without PVT. TMAO levels between the 3 groups were not significantly different. CONCLUSION We observed profound differences in gut microbiota between patients with ESLD and controls, but minimal differences between patients with ESLD with or without PVT. In our cohort, a gut-derived proinflammatory state was not associated with presence of PVT in patients with ESLD.
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Affiliation(s)
- Rali R Aleksandrova
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Lianne M Nieuwenhuis
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Naomi Karmi
- Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Shuyan Zhang
- Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Johann Casper Swarte
- Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Johannes R Björk
- Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ranko Gacesa
- Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Hans Blokzijl
- Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Margery A Connelly
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, North Carolina, USA
| | - Rinse K Weersma
- Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ton Lisman
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Surgery, University of Groningen, Surgical Research Laboratory, University Medical Center Groningen, Groningen, the Netherlands
| | - Eleonora A M Festen
- Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Vincent E de Meijer
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
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Ogory RO, Cumberford G, Adewole D. Ahiflower seed and its press cake as sources of nutrients for laying hens and omega-3 fatty acids in their eggs. Poult Sci 2025; 104:104936. [PMID: 40058003 PMCID: PMC11930598 DOI: 10.1016/j.psj.2025.104936] [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: 10/28/2024] [Revised: 02/15/2025] [Accepted: 02/21/2025] [Indexed: 03/28/2025] Open
Abstract
240 64-week-old Lohman LSL-Lite laying hens were used to evaluate the effect of ahiflower seed (AS) and its press cake (APC) on egg yolk fatty acid profile, production performance, apparent total tract nutrient digestibility (ATTD), egg quality, eggshell mineral content, and fecal microbiota composition for 12 weeks in a completely randomized design, with 6 replicates of 5 birds in a cage. The diets included a control (CD), CD supplemented with 10 % flaxseed (FS), and CD supplemented with AS at 1, 5, and 10 % inclusion levels and APC at 5, 10, and 15 % inclusion levels. Diet did not affect eggshell Ca (P=0.1168) and P (P=0.8212) levels, and feed conversion ratio (P=0.136), but the 10 % FS reduced body weight gain (P=0.044), hen day egg production (P= 0.000) and feed intake (P<.0001) compared to other treatments. The yolk lightness L* was reduced (P=0.030) by 5 % APC compared to 10 % APC, redness a* was reduced (P= 0.002) by 10 % FS and 15 %APC compared to 10 %APC, CD, and 1 % AS. The 10 % FS and 15 %APC also reduced (P<0.001) yellowness *b compared to 1 %AS and 5 %APC. Apparent metabolizable energy (AME) and nitrogen-corrected apparent metabolizable energy (AMEn) increased (P<0.001) in 10 %FS and all AS and APC levels compared to CD. Compared to CD (87 %), ATTD of energy was increased (P<0.001) in hens fed 10 %FS (93 %), 1 %AS (93 %), and 15 %APC (92 %). However, 10 %FS (78.7 %) and 1 %AS (81.7 %) had higher (P=0.011) ATTD of P than 10 %APC (64.6 %). Similarly, ATTD of Ca was reduced (P<0.001) in hens fed 10 %APC compared to CD and 10 %AS. Compared to other treatments, total n-3 and stearidonic acids were increased (P<0.001) by 10 %FS and 10 %AS, respectively, and the total n-6 FAs and linoleic acid were highest (P=0.001) in 15 %APC. Both 10 %AS and 10 %FS increased (P<0.001) eicosapentaenoic, docosahexaenoic, and alpha-linolenic acid, compared to CD. The n-6/n-3 ratio was reduced (P<0.001) by 10 %FS and 10 %AS compared to APC and CD. Dietary treatments modulated fecal microbiota differently, but notably, Lactobacillus was more abundant when hens were fed 5 %AS compared to other treatments. In conclusion, the dietary supplementation of 10 %AS increased n3-FAs deposition in eggs similar to 10 %FS. However, 10 %FS reduced production performance. All levels of AS and APC increased diet metabolizable energy with no negative effect on production performance.
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Affiliation(s)
- Roseline O Ogory
- Department of Animal and Poultry Science, College of Agriculture and Bioresources, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada
| | - Greg Cumberford
- Natures Crops International, 12682 Route 6, PO Box 248, Kensington, PE C0B 1M0, Canada
| | - Deborah Adewole
- Department of Animal and Poultry Science, College of Agriculture and Bioresources, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada.
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Seifert A, Ingram K, Eko EN, Nunziato J, Ahrens M, Howell BR. Impact of maternal obesity and mode of delivery on the newborn skin and oral microbiomes. J Med Microbiol 2025; 74. [PMID: 40208663 DOI: 10.1099/jmm.0.002000] [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: 04/11/2025] Open
Abstract
Introduction. Previous studies have shown vast differences in the skin and oral microbiomes of newborns based on delivery method [Caesarean section (C-section) vs vaginal]. Exposure to or absence of certain bacteria during delivery can impact the neonate's future susceptibility to infections, allergies or autoimmunity by altering immune functions. Few studies have focused on the impact of maternal obesity on the variations of newborn skin and oral microbiomes. Obese pregnant women typically have a higher vaginal microbiome diversity, and their pregnancies are at higher risk for adverse outcomes and complications.Hypothesis. We hypothesized that the skin and oral microbiomes of newborns born to obese mothers would include more diverse, potentially pathogenic bacteria and that the skin and oral microbiome in C-section delivered newborns would be less diverse than vaginally delivered newborns.Aim. We aim to begin to establish maternal obesity and mode of delivery as factors contributing to increased risk for negative newborn outcomes through impacts on newborn bacterial dysbiosis.Methodology. A skin swab was collected immediately following delivery of 39 newborns from 13 healthy weight body mass index (BMI 18.50-24.99), 11 overweight (BMI 25.0-29.99) and 15 obese (BMI ≥30.00) pregnant participants. An oral swab was collected immediately following delivery for 38 of these newborns from 13 healthy weight, 10 overweight and 15 obese pregnant participants. Bacterial genera were identified via 16S rRNA amplicon sequencing.Results. The newborn skin microbiome was comprised of typical skin bacteria (i.e. Corynebacterium). Newborns of obese participants had a higher relative abundance of Peptoniphilus in their skin microbiome compared to newborns of healthy weight participants (P=0.007). Neonates born via C-section had a higher relative abundance of Ureaplasma in their oral microbiome compared to neonates delivered vaginally (P=0.046).Conclusion. We identified differences in the newborn skin and oral microbiomes based on pre-pregnancy BMI and method of delivery. These differences could be linked to an increased risk of allergies, autoimmune disease and infections. Future longitudinal studies will be crucial in determining the long-term impact of these specific genera on newborn outcomes. Understanding these connections could lead to targeted interventions that reduce the risk of adverse outcomes and improve overall health trajectory.
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Affiliation(s)
| | - Kelly Ingram
- Virginia Tech Carilion School of Medicine, Roanoke, VA, USA
| | | | - Jaclyn Nunziato
- Virginia Tech Carilion School of Medicine, Roanoke, VA, USA
- Carilion Clinic, Roanoke, VA, USA
| | - Monica Ahrens
- Department of Statistics at Virginia Tech, Blacksburg, VA, USA
| | - Brittany R Howell
- Fralin Biomedical Research Institute at VTC, Roanoke, VA, USA
- Department of Human Development and Family Science, Virginia Tech, Blacksburg, VA, USA
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Wei X, Tang D. Effect of Bacteroides on Crohn's disease. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:393-402. [PMID: 39586813 DOI: 10.1055/a-2435-2659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
Crohn's disease (CD), also known as cicatrizing enteritis, is an inflammatory bowel disease that occurs in the distal ileum and right colon of unknown cause and is also called inflammatory bowel disease (IBD) with ulcerative colitis (UC). In recent years, intestinal biota have been confirmed to play a significant role in various gastrointestinal diseases. Studies have found that intestinal microbiota disorders are closely associated with the onset and progression of Crohn's disease. Bacteroidetes, the second largest microbiota in the intestine, are crucial for equilibrium in the microbiota and intestinal environment. Certain Bacteroides can induce the development of Crohn's disease and aggravate intestinal inflammation directly or through their metabolites. Conversely, certain Bacteroides can reduce intestinal inflammation and symptoms of Crohn's disease. This article reviews the effect of several intestinal Bacteroides in the onset and progression of Crohn's disease and their impact on its treatment.
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Affiliation(s)
- Xuanyu Wei
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University, Yangzhou, China
| | - Dong Tang
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University, Yangzhou, China
- Department of General Surgery, Institute of General Surgery, Northern Jiangsu People's Hospital, Nanjing University, Yangzhou, China
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Tufail MA, Schmitz RA. Exploring the Probiotic Potential of Bacteroides spp. Within One Health Paradigm. Probiotics Antimicrob Proteins 2025; 17:681-704. [PMID: 39377977 PMCID: PMC11925995 DOI: 10.1007/s12602-024-10370-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/25/2024] [Indexed: 03/21/2025]
Abstract
Probiotics are pivotal in maintaining or restoring the balance of human intestinal microbiota, a crucial factor in mitigating diseases and preserving the host's health. Exploration into Bacteroides spp. reveals substantial promise in their development as next-generation probiotics due to their profound interaction with host immune cells and capability to regulate the microbiome's metabolism by significantly impacting metabolite production. These beneficial bacteria exhibit potential in ameliorating various health issues such as intestinal disorders, cardiovascular diseases, behavioral disorders, and even cancer. Though it's important to note that a high percentage of them are as well opportunistic pathogens, posing risks under certain conditions. Studies highlight their role in modifying immune responses and improving health conditions by regulating lymphocytes, controlling metabolism, and preventing inflammation and cancer. The safety and efficacy of Bacteroides strains are currently under scrutiny by the European Commission for authorization in food processing, marking a significant step towards their commercialization. The recent advancements in bacterial isolation and sequencing methodologies, coupled with the integration of Metagenome-Assembled Genomes (MAGs) binning from metagenomics data, continue to unveil the potential of Bacteroides spp., aiding in the broader understanding and application of these novel probiotics in health and disease management.
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Affiliation(s)
- Muhammad Aammar Tufail
- Institut für Allgemeine Mikrobiologie, Christian-Albrechts-Universität zu Kiel, 24118, Kiel, Germany.
| | - Ruth A Schmitz
- Institut für Allgemeine Mikrobiologie, Christian-Albrechts-Universität zu Kiel, 24118, Kiel, Germany.
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Jing Y, Wang Q, Bai F, Li Z, Li Y, Liu W, Yan Y, Zhang S, Gao C, Yu Y. Age-related alterations in gut homeostasis are microbiota dependent. NPJ Biofilms Microbiomes 2025; 11:51. [PMID: 40133348 PMCID: PMC11937415 DOI: 10.1038/s41522-025-00677-y] [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: 06/04/2024] [Accepted: 02/26/2025] [Indexed: 03/27/2025] Open
Abstract
Accumulating data suggest that remodeling aged gut microbiota improves aging-related imbalance in intestinal homeostasis. However, evidence in favor of the beneficial effect of remodeling gut microbiota on intestinal stress and immune responses during aging is scarce. The current study revealed that old mice presented impaired gut barrier integrity. Transcriptome sequencing coupled with bioinformatics analysis revealed that aging altered gene expression profiles of the colon and mesenteric lymph nodes, which are involved mainly in stress and immune responses, respectively. Notably, gut microbiota was closely related to the differentially expressed genes. Microbiota depletion in old mice ameliorated gut barrier integrity and partially reversed the inflammatory factors upregulated in aging mice. Furthermore, fecal microbiota transplantation from young mice to old mice resulted in a significant improvement in intestinal barrier integrity and immune homeostasis. These findings highlight the potential of microbiota-targeted interventions on aging-related physiological processes and call for further investigation.
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Affiliation(s)
- Yingli Jing
- China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
| | - Qiuying Wang
- China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
| | - Fan Bai
- China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
| | - Zihan Li
- China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
| | - Yan Li
- China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
| | - Weijin Liu
- China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
| | - Yitong Yan
- China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
| | - Shuangyue Zhang
- China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
| | - Chen Gao
- China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
| | - Yan Yu
- China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China.
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.
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Chevalley T, Dübi M, Fumeaux L, Merli MS, Sarre A, Schaer N, Simeoni U, Yzydorczyk C. Sexual Dimorphism in Cardiometabolic Diseases: From Development to Senescence and Therapeutic Approaches. Cells 2025; 14:467. [PMID: 40136716 PMCID: PMC11941476 DOI: 10.3390/cells14060467] [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: 02/12/2025] [Revised: 03/03/2025] [Accepted: 03/14/2025] [Indexed: 03/27/2025] Open
Abstract
The global incidence and prevalence of cardiometabolic disorders have risen significantly in recent years. Although lifestyle choices in adulthood play a crucial role in the development of these conditions, it is well established that events occurring early in life can have an important effect. Recent research on cardiometabolic diseases has highlighted the influence of sexual dimorphism on risk factors, underlying mechanisms, and response to therapies. In this narrative review, we summarize the current understanding of sexual dimorphism in cardiovascular and metabolic diseases in the general population and within the framework of the Developmental Origins of Health and Disease (DOHaD) concept. We explore key risk factors and mechanisms, including the influence of genetic and epigenetic factors, placental and embryonic development, maternal nutrition, sex hormones, energy metabolism, microbiota, oxidative stress, cell death, inflammation, endothelial dysfunction, circadian rhythm, and lifestyle factors. Finally, we discuss some of the main therapeutic approaches, responses to which may be influenced by sexual dimorphism, such as antihypertensive and cardiovascular treatments, oxidative stress management, nutrition, cell therapies, and hormone replacement therapy.
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Affiliation(s)
| | | | | | | | | | | | | | - Catherine Yzydorczyk
- Developmental Origins of Health and Disease (DOHaD) Laboratory, Division of Pediatrics, Department Woman-Mother-Child, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland; (T.C.); (M.D.); (L.F.); (M.S.M.); (A.S.); (N.S.)
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Rodríguez-Moro G, Cabrera-Rubio R, Selma-Royo M, Gómez-Morlote JA, Collado MC, Abril N, García-Barrera T. Modulation of the gut microbiota and the microbial-produced gut metabolites by diclofenac exposure and selenium supplementation. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2025:10.1007/s11356-025-36233-6. [PMID: 40102351 DOI: 10.1007/s11356-025-36233-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 03/03/2025] [Indexed: 03/20/2025]
Abstract
Diclofenac (DCF) exposure is of great concern due to the ecotoxicological risk linked with a decline of vulture populations in Southeast Asia, but also because it can affect the reproduction and neurotoxicity in mammals. Otherwise, selenium (Se) is an antioxidant essential element with key roles in health and with antagonistic action against pollutants, but in some cases with a synergistic effect. To investigate the potential intertwined mechanisms between DCF, Se, and gut microbiota, gut metabolomic and gut microbiota profiles were determined in mice after DCF exposure and Se supplementation. Speciation of selenoproteins in plasma was carried out by isotopic dilution analysis to quantify the levels of selenoproteins. Significant differences in the levels of 79% of the gut metabolites were determined after DCF exposure. The most significant altered pathway in DCF and DCF-Se groups is the primary bile biosynthesis, being the only pathway altered in mice exposed to DCF, while in DCF-Se, the metabolism of galactose and linoleic acid is also altered. Moreover, specific associations between specific gut microbiota and metabolites were determined in the studied mice groups suggesting intertwined mechanisms. Selenium supplementation modulated the gut metabolic and microbiota profiles affected by DCF.
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Affiliation(s)
- Gema Rodríguez-Moro
- Department of Chemistry, Faculty of Experimental Sciences, Research Center of Natural Resources, Health and the Environment (RENSMA), University of Huelva, Fuerzas Armadas Ave, 21007, Huelva, Spain
| | - Raúl Cabrera-Rubio
- Department of Biotechnology, Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC), Agustin Escardino 7, 46980, Paterna, Valencia, Spain
| | - Marta Selma-Royo
- Department of Biotechnology, Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC), Agustin Escardino 7, 46980, Paterna, Valencia, Spain
| | - José Antonio Gómez-Morlote
- Department of Chemistry, Faculty of Experimental Sciences, Research Center of Natural Resources, Health and the Environment (RENSMA), University of Huelva, Fuerzas Armadas Ave, 21007, Huelva, Spain
| | - Maria Carmen Collado
- Department of Biotechnology, Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC), Agustin Escardino 7, 46980, Paterna, Valencia, Spain
| | - Nieves Abril
- Department of Biochemistry and Molecular Biology, University of Córdoba, Campus de Rabanales, Edificio Severo Ochoa, 14071, Córdoba, Spain
| | - Tamara García-Barrera
- Department of Chemistry, Faculty of Experimental Sciences, Research Center of Natural Resources, Health and the Environment (RENSMA), University of Huelva, Fuerzas Armadas Ave, 21007, Huelva, Spain.
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Yang H, Gan Y, Jiang S, Zhu X, Xia Y, Gong D, Xie X, Gong Y, Zhang Y, Lei Q, Wang M, Li J. Genomic alterations in Bacteroides fragilis favor adaptation in colorectal cancer microenvironment. BMC Genomics 2025; 26:269. [PMID: 40102781 PMCID: PMC11921484 DOI: 10.1186/s12864-025-11421-3] [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: 11/11/2024] [Accepted: 02/28/2025] [Indexed: 03/20/2025] Open
Abstract
BACKGROUND The occurrence and development of colorectal cancer (CRC) is an incredibly long process that involves continuous changes in the tumor microenvironment. These constant changes may ultimately result in genetic alterations and changes in the metabolic processes of some symbiotic bacteria as a way to adapt to the changing environment. Patients with CRC exhibit an altered abundance of Bacteroides fragilis (B. fragilis) as indicated by several studies. To better understand the genomic characteristics and virulence spectrum of B. fragilis strains in tumor tissues, B. fragilis strains were isolated from tumor and paracancerous tissues of CRC patients. METHODS The isolates were identified using 16 S rRNA sequencing, morphological analysis, physiological and biochemical characterization and PCR, and they were then subjected to whole genome sequencing (WGS) analysis. RESULTS A strain of B. fragilis enterotoxin (BFT) bft1-producing ZY0302 and a non-enterotoxin-producing B. fragilis ZY0804 were isolated from cancerous and paraneoplastic tissues, respectively. Analysis based on the core and nonessential genes showed that the genomic profiles of the isolates, ZY0302 and ZY0804, differed from those of B. fragilis from other tissue sources. This core and the co-evolution of non-essential genes may be the result of their adaptation to fluctuations in the tumor microenvironment and enhancing their survival. In addition, the ZY0302 and ZY0804 genomes underwent extensive horizontal gene transfer and varying degrees of genomic rearrangements, inversions, insertions, and deletion events, which may favor the enhancement of bacteria's ability to adapt to environmental changes. For instance, the virulence factors, such as the capsular biosynthesis gene clusters and components of the type IV secretion system, acquired through horizontal gene transfer, may facilitated B. fragilis in evading immune responses and managing oxidative stress. Moreover, our analysis revealed that multiple virulence factors identified in the isolates were mainly involved in bacterial adhesion and colonization, oxidative stress, iron acquisition, and immune evasion. This observation is worth noting given that enzymes such as neuraminidase, lipase, hemolysin, protease, and phosphatase, along with genes responsible for LPS biosynthesis, which are recognized for their association with the virulence of B. fragilis, were prevalent among the isolates. CONCLUSIONS In summary, it is our assertion that the alterations observed in both core and nonessential genes of B. fragilis, which have been isolated from tissues of colorectal cancer patients, along with significant instances of horizontal gene transfer to the genome, are likely intended to enhance adaptation to the evolving conditions of the tumor microenvironment. This study may provide new insights into the interaction between B. fragilis and the CRC microenvironment.
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Affiliation(s)
- Hao Yang
- Institute of Zoonosis, College of Public Health, Zunyi Medical University, Zunyi, Guizhou, China
| | - Yu Gan
- Institute of Zoonosis, College of Public Health, Zunyi Medical University, Zunyi, Guizhou, China
| | - Shenghai Jiang
- Institute of Zoonosis, College of Public Health, Zunyi Medical University, Zunyi, Guizhou, China
| | - Xianchang Zhu
- Institute of Zoonosis, College of Public Health, Zunyi Medical University, Zunyi, Guizhou, China
| | - Yang Xia
- Southwest Guizhou Vocational and Technical College, Xingyi, Guizhou, China
| | - Dengmei Gong
- Institute of Zoonosis, College of Public Health, Zunyi Medical University, Zunyi, Guizhou, China
| | - Xianrang Xie
- Institute of Zoonosis, College of Public Health, Zunyi Medical University, Zunyi, Guizhou, China
| | - Yao Gong
- Institute of Zoonosis, College of Public Health, Zunyi Medical University, Zunyi, Guizhou, China
| | - Yi Zhang
- Institute of Zoonosis, College of Public Health, Zunyi Medical University, Zunyi, Guizhou, China
- Key Laboratory of Maternal & Child Health and Exposure Science of Guizhou Higher Education Institutes, Zunyi, Guizhou, China
| | - Qian Lei
- Institute of Zoonosis, College of Public Health, Zunyi Medical University, Zunyi, Guizhou, China
| | - Maijian Wang
- Institute of Gastroenterology, Affiliate Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
- , No. 149, Dalian Road,, Zunyi City, 563003, Guizhou Province, China.
| | - Jida Li
- Institute of Zoonosis, College of Public Health, Zunyi Medical University, Zunyi, Guizhou, China.
- Key Laboratory of Maternal & Child Health and Exposure Science of Guizhou Higher Education Institutes, Zunyi, Guizhou, China.
- , No. 6, Xuefu West Road, Xinpu New District, Zunyi City, 563000, Guizhou Province, China.
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Li H, Aguilar Meza L, Shahi SK, Zhang Z, Wen W, Hu D, Lin H, Mangalam A, Luo J. Effects of alcohol on gut microbiome in adolescent and adult MMTV-Wnt1 mice. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.03.17.643801. [PMID: 40166271 PMCID: PMC11957038 DOI: 10.1101/2025.03.17.643801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Breast cancer is the most commonly diagnosed cancer in women worldwide, with alcohol consumption recognized as a significant risk factor. While epidemiological studies consistently show a positive correlation between alcohol consumption and increased breast cancer risk, the underlying mechanisms remain unclear. Recent evidence suggests that the gut microbiome-the diverse collection of microorganisms, including bacteria, viruses, and fungi, residing in the gastrointestinal tract-plays a pivotal role in systemic health and disease. This is achieved through its regulation of key physiological processes such as metabolism, immune function, and inflammatory responses. Disruption of the gut microbiome (dysbiosis) has recently been implicated in the development of breast cancer. We hypothesized that alcohol exposure induces gut dysbiosis, which in turn drives systemic inflammation and carcinogenic processes. Previously, we demonstrated that alcohol exposure promotes mammary tumor growth and aggressiveness in MMTV-Wnt1 (Wnt1) transgenic mice, an established model for investigating mechanisms of alcohol-induced tumor promotion. In this study, we sought to determine whether alcohol exposure induces gut dysbiosis in adolescent and adult Wnt1 transgenic mice and their wild-type FVB counterparts. Our findings revealed that alcohol exposure significantly reduced microbiome richness in adult Wnt1 and FVB mice. Alcohol exposure also markedly altered microbiome composition in adolescents and adults in both strains. Additionally, we identified specific microbial taxa that were significantly affected by alcohol exposure. These results demonstrate that alcohol disrupts the gut microbiome in a preclinical breast cancer model, providing insights into the potential role of gut dysbiosis in alcohol-induced mammary tumor promotion and offering avenues for future research.
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Wang S, Niu W, Lv T, Xie K. Traceability of septic shock caused by phocaeicola vulgatus: a rare case report. BMC Infect Dis 2025; 25:364. [PMID: 40089680 PMCID: PMC11910868 DOI: 10.1186/s12879-025-10771-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 03/10/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND Phocaeicola vulgatus (P.vulgatus) is a member of Bacteroides fragilis Group(BFG). Septic shock caused by P.vulgatus has not been reported yet. In recent years, BFG have attracted much clinical attention. BFG are the commensal microbiota residing in human mucosal sites, most notably the gut, that provide several benefits to healthy hosts. Yet BFG can cause devastating infections when they gain access to normally sterile body compartments following trauma, surgery, or mucosal barrier disruption. CASE PRESENTATION We report a case of septic shock event in a middle-aged male who underwent surgical intervention for a gallbladder mass incidentally detected during routine abdominal CT screening. P.vulgatus was isolated and cultured from blood sample and abdominal drainage fluid after surgery. We further performed the Metagenomic Next-Generation Sequencing (mNGS) with pathological slices of colon and hepatobiliary tissue, and result of mNGS also showed P.vulgatus. The patient was treated with comprehensive therapies and had a good outcome. CONCLUSION To the best of our knowledge, septic shock secondary to P.vulgatus infection originating from non-gastrointestinal area represents an rare clinical condition. We realized that research on BFG should not only focus on its positive effects on the intestine, but also on its potential pathogenicity, including intra-abdominal infections, abscesses, and bloodstream infection.
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Affiliation(s)
- Shouping Wang
- Department of Intensive Care Unit, West China Hospital, Sichuan University, Chengdu, China
| | - Wang Niu
- Department of Anesthesiology, West China Hospital, Sichuan University and the Research Units of West China (2018RU012), Chinese Academy of Medical Sciences, Chengdu, China
| | - Tao Lv
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
- Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Kunlin Xie
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
- Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
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Liu M, Ji YL, Hu YJ, Su YX, Yang J, Wang XY, Chu HY, Zhang X, Dong SJ, Yang H, Liu YH, Zhou SM, Guo LP, Ran Y, Li YN, Zhao JW, Zhang ZG, Piao MY, Zhou L. Lactococcus garvieae aggravates cholestatic liver disease by increasing intestinal permeability and enhancing bile acid reabsorption. World J Gastroenterol 2025; 31:101014. [PMID: 40093673 PMCID: PMC11886528 DOI: 10.3748/wjg.v31.i10.101014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 12/19/2024] [Accepted: 02/05/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Although an association between gut microbiota and cholestatic liver disease (CLD) has been reported, the precise functional roles of these microbes in CLD pathogenesis remain largely unknown. AIM To explore the function of gut microbes in CLD pathogenesis and the effects of gut microbiota on intestinal barrier and bile acid (BA) metabolism in CLD. METHODS Male C57BL/6J mice were fed a 0.05% 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet for 2 weeks to induce CLD. The sterile liver tissues of mice were then meticulously harvested, and bacteria in homogenates were identified through culture methods. Furthermore, 16S ribosomal DNA sequencing was employed to analyze sterile liver samples collected from eight patients with primary biliary cholangitis (PBC) and three control individuals with hepatic cysts. The functional roles of the identified bacteria in CLD pathogenesis were assessed through microbiota transfer experiments, involving the evaluation of changes in intestinal permeability and BA dynamics. RESULTS Ligilactobacillus murinus (L. murinus) and Lactococcus garvieae (L. garvieae) were isolated from the bacterial culture of livers from CLD mice. L. murinus was prevalently detected in PBC patients and controls, whereas L. garvieae was detected only in patients with PBC but not in controls. Mice inoculated with L. garvieae exhibited increased susceptibility to experimental CLD, with both in vitro and in vivo indicating that L. garvieae disrupted the intestinal barrier function by down-regulating the expression of occludin and zonula occludens-1. Moreover, L. garvieae administration significantly upregulated the expression of the apical sodium-dependent BA transporter in the terminal ileum and increased serum BA levels. CONCLUSION L. garvieae contributes to excessive BA-induced hepatobiliary injury and liver fibrosis by increasing intestinal permeability and enhancing BA reabsorption.
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Affiliation(s)
- Man Liu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Ying-Lan Ji
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Yu-Jie Hu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Ying-Xi Su
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Jie Yang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin 300308, China
| | - Xiao-Yi Wang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin 300170, China
| | - Hong-Yu Chu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Xue Zhang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Shi-Jing Dong
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Hui Yang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Yu-Hang Liu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Si-Min Zhou
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Li-Ping Guo
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Ying Ran
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Yan-Ni Li
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Jing-Wen Zhao
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Zhi-Guang Zhang
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Mei-Yu Piao
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Lu Zhou
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300070, China
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Alizadeh M, Oladokun S, Fletcher C, Boodhoo N, Fazel F, Shojadoost B, Raj S, Zheng J, Abdelaziz K, Sharif S. Evaluating the protective effects of the Toll-like receptor (TLR) 21 ligand, CpG ODN, against necrotic enteritis in broiler chickens. PLoS One 2025; 20:e0319404. [PMID: 40080496 PMCID: PMC11906054 DOI: 10.1371/journal.pone.0319404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 02/01/2025] [Indexed: 03/15/2025] Open
Abstract
Necrotic enteritis (NE), caused by Clostridium perfringens (C. perfringens), presents a challenge to the global broiler industry. Evidence suggests that Toll-like receptor (TLR) ligands can enhance the immune responses in chickens and protect them against infectious diseases. This study investigated the protective effects of TLR21 ligand class B CpG oligonucleotides (ODN) against NE in broiler chickens. On day 21 of age, chickens were injected with 50 or 100 μg CpG intramuscularly, and one group was injected with 50 μg CpG followed by a booster dose on day 22. Subsequently, birds were orally challenged with C. perfringens twice daily for three days, starting on day 22. On day 22, intestinal samples were collected for gene expression analysis. On day 25, all birds were euthanized, intestinal lesions were scored, and tissue samples were collected from the intestine for gene expression analysis, lymphocyte subset determination, and histomorphological analysis. Cecal contents were also collected for microbiome analysis. The results demonstrated that CpG pre-treatment, either at a single dose of 100 μg or two doses of 50 μg per bird, reduced lesion scores compared to the positive control. C. perfringens infection increased crypt depth in both the jejunum and ileum in the positive control group compared to both the CpG-treated group. At 22 days of age, CpG administration at doses of 100 μg per bird enhanced expression of TLR21, interleukin (IL)-2, CXCL8, IL-10, and interferon (IFN)-γ mRNA transcripts in both the jejunum and ileum. Additionally, at 25 days of age, the group pretreated with two doses of 50 μg of CpG per bird showed increased expression of all cytokines in both the jejunum and ileum compared to the control groups. The percentage of intestinal lymphocytes was not affected by CpG pre-treatment. However, CpG pretreatment at doses of 100 μg resulted in a higher abundance of the members of families Lactobacillaceae and Bacteroidaceae, which are crucial for maintaining gut health. In conclusion, our findings suggest that pretreatment of chickens with intramuscular administration of CpG may be effective in maintaining gut health during C. perfringens infection.
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Affiliation(s)
- Mohammadali Alizadeh
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
| | - Samson Oladokun
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
| | - Charlotte Fletcher
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
| | - Nitish Boodhoo
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
| | - Fatemeh Fazel
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
| | | | - Sugandha Raj
- National Centre for Foreign Animal Disease, Winnipeg, Manitoba, Canada
| | - Jiayu Zheng
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
| | - Khaled Abdelaziz
- Clemson University School of Health Research (CUSHR), Clemson, South Carolina, United States of America
- Department of Animal and Veterinary Science, Clemson University, Clemson, South Carolina, United States of America
| | - Shayan Sharif
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
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Xiong Y, Lu X, Li B, Xu S, Fu B, Sha Z, Tian R, Yao R, Li Q, Yan J, Guo D, Cong Z, Du Y, Lin X, Wu H. Bacteroides Fragilis Transplantation Reverses Reproductive Senescence by Transporting Extracellular Vesicles Through the Gut-Ovary Axis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2409740. [PMID: 39805029 PMCID: PMC11884595 DOI: 10.1002/advs.202409740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 11/20/2024] [Indexed: 01/16/2025]
Abstract
The diverse and dynamic population of microorganisms present in the gut microbiota may affect host health. There are evidences to support the role of gut microbiota as a key player in reproductive development. Unfortunately, the relationship between reproductive disorders caused by aging and gut microbiota remains largely unknown. Here, it is shown for the first time that gut microorganism Bacteroides fragilis (BF) transplantation ameliorates ovarian aging by transporting extracellular vesicles (EVs) through the gut-ovary axis. Mechanistically, miR-1246 is enriched in EVs derived from BF-treated intestinal cells, and these miR-1246-enriched EVs are transferred to ovaries, thereby effectively improving reproductive senescence by reducing oxidative stress in the ovaries. Specifically, miR-1246 reduces the ubiquitination of p62 and stabilizes the protein level of p62 by targeting E3 ligase SKP2. Then Keap1-Nrf2 complex is dissociated and Keap1 is recruited to form the p62-Keap1 complex. With the dissociation of Keap1-Nrf2 complex, Nrf2 is released and activated, thus promoting the transcription of antioxidant enzymes and relieving reproductive senescence. Collectively, the data indicates that intestinal cell-derived EVs serve as natural information carriers in the crosstalk between the gut and the ovary, and intestinal microorganism transplantation is a promising approach for the treatment of ovarian dysfunction diseases.
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Affiliation(s)
- Yan Xiong
- School of Life SciencesChongqing UniversityChongqing401331China
| | - Xiaoxue Lu
- Department of Clinical Microbiology and ImmunologyCollege of Pharmacy and Medical LaboratoryArmy Medical University (Third Military Medical University)Chongqing400038China
| | - Bohao Li
- School of Life SciencesChongqing UniversityChongqing401331China
| | - Shiyao Xu
- School of Life SciencesChongqing UniversityChongqing401331China
| | - Beibei Fu
- School of Life SciencesChongqing UniversityChongqing401331China
| | - Zhou Sha
- School of Life SciencesChongqing UniversityChongqing401331China
| | - Rong Tian
- Department of pathologyChongqing Hygeia HospitalChongqing401331China
| | - Rui Yao
- Department of pathologyChongqing Hygeia HospitalChongqing401331China
| | - Qian Li
- Department of Clinical Microbiology and ImmunologyCollege of Pharmacy and Medical LaboratoryArmy Medical University (Third Military Medical University)Chongqing400038China
| | - Jingmin Yan
- Department of Clinical Microbiology and ImmunologyCollege of Pharmacy and Medical LaboratoryArmy Medical University (Third Military Medical University)Chongqing400038China
| | - Dong Guo
- School of Life SciencesChongqing UniversityChongqing401331China
| | - Zixuan Cong
- School of Life SciencesChongqing UniversityChongqing401331China
| | - Yongliang Du
- School of Life SciencesChongqing UniversityChongqing401331China
| | - Xiaoyuan Lin
- Department of Clinical Microbiology and ImmunologyCollege of Pharmacy and Medical LaboratoryArmy Medical University (Third Military Medical University)Chongqing400038China
| | - Haibo Wu
- School of Life SciencesChongqing UniversityChongqing401331China
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48
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Vendrell-Fernández S, Beamud B, Abou Haydar Y, Am de Sousa J, Burlaud-Gaillard J, Kornobis E, Raynal B, Vinh J, Bikard D, Ghigo JM. Incomplete lytic cycle of a widespread Bacteroides bacteriophage leads to the formation of defective viral particles. PLoS Biol 2025; 23:e3002787. [PMID: 40163458 DOI: 10.1371/journal.pbio.3002787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 01/27/2025] [Indexed: 04/02/2025] Open
Abstract
Advances in metagenomics have led to the identification of new intestinal temperate bacteriophages. However, their experimental characterization remains challenging due to a limited understanding of their lysogenic-lytic cycle and the common lack of plaque formation in vitro. In this study, we investigated the hankyphage, a widespread transposable phage of prominent Bacteroides symbionts. Hankyphages spontaneously produced virions in laboratory conditions even in the absence of inducer, but virions did not show any evidence of infectivity. To increase virion production and raise the chances of observing infection events, we identified a master repressor of the hankyphage lytic cycle, RepCHP, whose silencing amplified hankyphage gene expression, and enhanced replicative transposition and virion production. However, attempts to infect or lysogenize new host cells with different capsular types remained unsuccessful. Transmission electron microscopy and capsid DNA sequencing revealed an abnormal virion morphology and incomplete DNA packaging of the hankyphage, suggesting that it cannot complete its assembly in laboratory conditions for reasons that are yet to be identified. Still, metavirome and phylogenetic analyses were suggestive of hankyphage horizontal transmission. We could also detect the activity of diversity-generating retroelements (DGRs) that mutagenize the hankyphage tail fiber, and likely contribute to its broad host range. This study sheds light on the life cycle of this abundant intestinal bacteriophage and highlights important gaps in our understanding of the factors required for the completion of its life cycle. Elucidating this puzzle will be critical to gain a better understanding of the hankyphage biology and ecological role.
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Affiliation(s)
- Sol Vendrell-Fernández
- Institut Pasteur, Université Paris-Cité, UMR CNRS 6047, Genetics of Biofilms Laboratory, Paris, France
| | - Beatriz Beamud
- Institut Pasteur, Université Paris-Cité, UMR CNRS 3525, Synthetic Biology Laboratory, Paris, France
| | - Yasmina Abou Haydar
- Institut Pasteur, Université Paris-Cité, UMR CNRS 6047, Genetics of Biofilms Laboratory, Paris, France
| | - Jorge Am de Sousa
- Institut Pasteur, Université Paris-Cité, Microbial Evolutionary Genomics Laboratory, Paris, France
| | | | - Etienne Kornobis
- Institut Pasteur, Université Paris Cité, Plateforme Technologique Biomics, Paris, France
- Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, Paris, France
| | - Bertrand Raynal
- Institut Pasteur, Université Paris-Cité, Molecular Biophysics Platform, Paris, France
| | - Joelle Vinh
- ESPCI Paris, PSL University, UAR CNRS 2051, Biological Mass Spectrometry and Proteomics, Paris, France
| | - David Bikard
- Institut Pasteur, Université Paris-Cité, UMR CNRS 3525, Synthetic Biology Laboratory, Paris, France
| | - Jean-Marc Ghigo
- Institut Pasteur, Université Paris-Cité, UMR CNRS 6047, Genetics of Biofilms Laboratory, Paris, France
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49
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Wang K, Hu Y, Wu Y, Xu J, Zhao Y, Yang J, Li X. The Therapeutic Potential of Gut-Microbiota-Derived Metabolite 4-Phenylbutyric Acid in Escherichia coli-Induced Colitis. Int J Mol Sci 2025; 26:1974. [PMID: 40076603 PMCID: PMC11901052 DOI: 10.3390/ijms26051974] [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: 12/15/2024] [Revised: 01/16/2025] [Accepted: 01/18/2025] [Indexed: 03/14/2025] Open
Abstract
Pathogenic Escherichia coli (E. coli) is a widely distributed pathogen that can cause varying degrees of zoonotic diseases, and infected animals often experience intestinal inflammation accompanied by diarrhea and dysbiosis. Previously, for the first time, we isolated Escherichia coli primarily of type B2 from a large-scale dairy farm in Yunnan, China. The 16s rRNA sequencing showed significant differences in the gut microbiota of calves infected with B2 E. coli, with higher abundance of harmful bacteria and lower abundance of beneficial bacteria compared with healthy calves. The metabolomics indicated that the concentrations of oxoadipic acid, 16-oxopalmitate, oerillyl alcohol, palmitoleic acid, and 4-phenylbutyrate (4-PBA) were significantly higher in the healthy group than in the infected group. The mouse model was established to assess the regulatory effect of 4-PBA on E. coli-induced colitis. Both oral administration of 4-PBA and fecal microbiota transplantation (FMT) had strong resistance to E. coli infection, improved survival rate and body weight, reduced intestinal tissue damage, decreased the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and restrained TLR4/MyD88/NF-κB pathway. Our study demonstrated that 4-PBA could relieve E. coli-induced colitis by improving gut microbiota structure and inhibiting the expression of pro-inflammatory cytokines through the TLR4/MyD88/NF-κB pathway. The present finding reveals the therapeutic potential of the gut-microbiota-derived metabolite 4-PBA for the treatment of colitis caused by E. coli.
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Affiliation(s)
| | | | | | | | | | - Jing Yang
- College of Veterinary Medicine, Yunnan Agricultural University, No. 452 Fengyuan Road, Panlong District, Kunming 650201, China; (K.W.); (Y.H.); (Y.W.); (J.X.); (Y.Z.)
| | - Xiaobing Li
- College of Veterinary Medicine, Yunnan Agricultural University, No. 452 Fengyuan Road, Panlong District, Kunming 650201, China; (K.W.); (Y.H.); (Y.W.); (J.X.); (Y.Z.)
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50
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Noureldein MH, Rumora AE, Teener SJ, Rigan DM, Hayes JM, Mendelson FE, Carter AD, Rubin WG, Savelieff MG, Feldman EL. Dietary Fatty Acid Composition Alters Gut Microbiome in Mice with Obesity-Induced Peripheral Neuropathy. Nutrients 2025; 17:737. [PMID: 40005065 PMCID: PMC11858455 DOI: 10.3390/nu17040737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Revised: 02/10/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Peripheral neuropathy (PN), a complication of diabetes and obesity, progresses through a complex pathophysiology. Lifestyle interventions to manage systemic metabolism are recommended to prevent or slow PN, given the multifactorial risks of diabetes and obesity. A high-fat diet rich in saturated fatty acids (SFAs) induces PN, which a diet rich in monounsaturated fatty acids (MUFAs) rescues, independent of weight loss, suggesting factors beyond systemic metabolism impact nerve health. Interest has grown in gut microbiome mechanisms in PN, which is characterized by a distinct microbiota signature that correlates with sciatic nerve lipidome. METHODS Herein, we postulated that SFA- versus MUFA-rich diet would impact gut microbiome composition and correlate with PN development. To assess causality, we performed fecal microbiota transplantation (FMT) from donor mice fed SFA- versus MUFA-rich diet to lean recipient mice and assessed metabolic and PN phenotypes. RESULTS We found that the SFA-rich diet altered the microbiome community structure, which the MUFA-rich diet partially reversed. PN metrics correlated with several microbial families, some containing genera with feasible mechanisms of action for microbiome-mediated effects on PN. SFA and MUFA FMT did not impact metabolic phenotypes in recipient mice although SFA FMT marginally induced motor PN. CONCLUSIONS The involvement of diet-mediated changes in the microbiome on PN and gut-nerve axis may warrant further study.
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Affiliation(s)
- Mohamed H. Noureldein
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
- NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA
| | - Amy E. Rumora
- Department of Neurology, Columbia University, New York, NY 10032, USA
| | - Samuel J. Teener
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
- NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA
| | - Diana M. Rigan
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
- NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA
| | - John M. Hayes
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
- NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA
| | - Faye E. Mendelson
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
- NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA
| | - Andrew D. Carter
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
- NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA
| | - Whitney G. Rubin
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
- NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA
| | - Masha G. Savelieff
- Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58202, USA
| | - Eva L. Feldman
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
- NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA
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