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1
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Dongre DS, Saha UB, Saroj SD. Exploring the role of gut microbiota in antibiotic resistance and prevention. Ann Med 2025; 57:2478317. [PMID: 40096354 PMCID: PMC11915737 DOI: 10.1080/07853890.2025.2478317] [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: 10/28/2024] [Revised: 02/24/2025] [Accepted: 02/27/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND/INTRODUCTION Antimicrobial resistance (AMR) and the evolution of multiple drug-resistant (MDR) bacteria is of grave public health concern. To combat the pandemic of AMR, it is necessary to focus on novel alternatives for drug development. Within the host, the interaction of the pathogen with the microbiome plays a pivotal role in determining the outcome of pathogenesis. Therefore, microbiome-pathogen interaction is one of the potential targets to be explored for novel antimicrobials. MAIN BODY This review focuses on how the gut microbiome has evolved as a significant component of the resistome as a source of antibiotic resistance genes (ARGs). Antibiotics alter the composition of the native microbiota of the host by favouring resistant bacteria that can manifest as opportunistic infections. Furthermore, gut dysbiosis has also been linked to low-dosage antibiotic ingestion or subtherapeutic antibiotic treatment (STAT) from food and the environment. DISCUSSION Colonization by MDR bacteria is potentially acquired and maintained in the gut microbiota. Therefore, it is pivotal to understand microbial diversity and its role in adapting pathogens to AMR. Implementing several strategies to prevent or treat dysbiosis is necessary, including faecal microbiota transplantation, probiotics and prebiotics, phage therapy, drug delivery models, and antimicrobial stewardship regulation.
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Affiliation(s)
- Devyani S. Dongre
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune, Maharashtra, India
| | - Ujjayni B. Saha
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune, Maharashtra, India
| | - Sunil D. Saroj
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune, Maharashtra, India
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2
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Cantu-Jungles TM, Agamennone V, Van den Broek TJ, Schuren FHJ, Hamaker B. Systematically-designed mixtures outperform single fibers for gut microbiota support. Gut Microbes 2025; 17:2442521. [PMID: 39704614 DOI: 10.1080/19490976.2024.2442521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 10/03/2024] [Accepted: 12/09/2024] [Indexed: 12/21/2024] Open
Abstract
Dietary fiber interventions to modulate the gut microbiota have largely relied on isolated fibers or specific fiber sources. We hypothesized that fibers systematically blended could promote more health-related bacterial groups. Initially, pooled in vitro fecal fermentations were used to design dietary fiber mixtures to support complementary microbial groups related to health. Then, microbial responses were compared for the designed mixtures versus their single fiber components in vitro using fecal samples from a separate cohort of 10 healthy adults. The designed fiber mixtures outperformed individual fibers in supporting bacterial taxa across donors resulting in superior alpha diversity and unexpected higher SCFA production. Moreover, unique shifts in community structure and specific taxa were observed for fiber mixtures that were not observed for single fibers, suggesting a synergistic effect when certain fibers are put together. Fiber mixture responses were remarkably more consistent than individual fibers across donors in promoting several taxa, especially butyrate producers from the Clostridium cluster XIVa. This is the first demonstration of synergistic fiber interactions for superior support of a diverse group of important beneficial microbes consistent across people, and unexpectedly high SCFA production. Overall, harnessing the synergistic potential of designed fiber mixtures represents a promising and more efficacious avenue for future prebiotic development.
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Affiliation(s)
- T M Cantu-Jungles
- Whistler Center for Carbohydrate Research, Department of Food Science, Purdue University, West Lafayette, IN, USA
| | - V Agamennone
- Microbiology and Systems Biology Group, The Netherlands Organization for Applied Scientific Research (TNO), Zeist, the Netherlands
| | - T J Van den Broek
- Microbiology and Systems Biology Group, The Netherlands Organization for Applied Scientific Research (TNO), Zeist, the Netherlands
| | - F H J Schuren
- Microbiology and Systems Biology Group, The Netherlands Organization for Applied Scientific Research (TNO), Zeist, the Netherlands
| | - B Hamaker
- Whistler Center for Carbohydrate Research, Department of Food Science, Purdue University, West Lafayette, IN, USA
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3
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Otani S, Louise Jespersen M, Brinch C, Duus Møller F, Pilgaard B, Egholm Bruun Jensen E, Leekitcharoenphon P, Aaby Svendsen C, Aarestrup AH, Sonda T, Sylvina TJ, Leach J, Piel A, Stewart F, Sapountzis P, Kazyoba PE, Kumburu H, Aarestrup FM. Genomic and functional co-diversification imprint African Hominidae microbiomes to signal dietary and lifestyle adaptations. Gut Microbes 2025; 17:2484385. [PMID: 40164980 PMCID: PMC11959905 DOI: 10.1080/19490976.2025.2484385] [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: 11/19/2024] [Revised: 01/27/2025] [Accepted: 03/20/2025] [Indexed: 04/02/2025] Open
Abstract
In the diverse landscape of African hominids, the obligate relationship between the host and its microbiome narrates signals of adaptation and co-evolution. Sequencing 546 African hominid metagenomes, including those from indigenous Hadza and wild chimpanzees, identified similar bacterial richness and diversity surpassing those of westernized populations. While hominids share core bacterial communities, they also harbor distinct, population-specific bacterial taxa tailored to specific diets, ecology and lifestyles, differentiating non-indigenous and indigenous humans and chimpanzees. Even amongst shared bacterial communities, several core bacteria have co-diversified to fulfil unique dietary degradation functions within their host populations. These co-evolutionary trends extend to non-bacterial elements, such as mitochondrial DNA, antimicrobial resistance, and parasites. Our findings indicate that microbiome-host co-adaptations have led to both taxonomic and within taxa functional displacements to meet host physiological demands. The microbiome, in turn, transcends its taxonomic interchangeable role, reflecting the lifestyle, ecology and dietary history of its host.
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Affiliation(s)
- Saria Otani
- Research group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Lyngby, Denmark
| | - Marie Louise Jespersen
- Research group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Lyngby, Denmark
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Christian Brinch
- Research group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Lyngby, Denmark
| | - Frederik Duus Møller
- Research group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Lyngby, Denmark
| | - Bo Pilgaard
- Department of Biotechnology and Biomedicine, Section for Protein Chemistry and Enzyme Technology, Technical University of Denmark, Lyngby, Denmark
| | - Emilie Egholm Bruun Jensen
- Research group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Lyngby, Denmark
| | - Pimlapas Leekitcharoenphon
- Research group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Lyngby, Denmark
| | - Christina Aaby Svendsen
- Research group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Lyngby, Denmark
| | - Amalie H. Aarestrup
- Research group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Lyngby, Denmark
| | - Tolbert Sonda
- Biotechnology Research Laboratory, Kilimanjaro Clinical Research Institute (KCRI), Moshi, Tanzania
- Kilimanjaro Christian Medical Centre (KCMC), Moshi, Tanzania
- Department of Microbiology, Kilimanjaro Christian Medical University College (KCMUCo), Moshi, Tanzania
| | - Teresa J. Sylvina
- National Academies of Sciences, Engineering and Medicine, Washington, DC, USA
- Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, State College, PA, USA
| | - Jeff Leach
- Microbiome Network and Department of Agricultural Biology, Colorado State University, Fort Collins, CO, USA
| | - Alexander Piel
- Department of Human Origins, Max Planck Institute of Evolutionary Anthropology, Leipzig, Germany
- Department of Anthropology, University College London, London, UK
| | - Fiona Stewart
- Department of Human Origins, Max Planck Institute of Evolutionary Anthropology, Leipzig, Germany
- Department of Anthropology, University College London, London, UK
- School of Biological and Environmental Sciences, Liverpool John Moores University, Liverpool, UK
| | | | - Paul E. Kazyoba
- National Institute for Medical Research, Dar-Es-Salaam, Tanzania
| | - Happiness Kumburu
- Biotechnology Research Laboratory, Kilimanjaro Clinical Research Institute (KCRI), Moshi, Tanzania
| | - Frank M. Aarestrup
- Research group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Lyngby, Denmark
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4
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Aboulalazm FA, Kazen AB, deLeon O, Müller S, Saravia FL, Lozada-Fernandez V, Hadiono MA, Keyes RF, Smith BC, Kellogg SL, Grobe JL, Kindel TL, Kirby JR. Reutericyclin, a specialized metabolite of Limosilactobacillus reuteri, mitigates risperidone-induced weight gain in mice. Gut Microbes 2025; 17:2477819. [PMID: 40190120 PMCID: PMC11980487 DOI: 10.1080/19490976.2025.2477819] [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: 04/26/2024] [Revised: 01/14/2025] [Accepted: 03/05/2025] [Indexed: 04/11/2025] Open
Abstract
The role of xenobiotic disruption of microbiota, corresponding dysbiosis, and potential links to host metabolic diseases are of critical importance. In this study, we used a widely prescribed antipsychotic drug, risperidone, known to influence weight gain in humans, to induce weight gain in C57BL/6J female mice. We hypothesized that microbes essential for maintaining gut homeostasis and energy balance would be depleted following treatment with risperidone, leading to enhanced weight gain relative to controls. Thus, we performed metagenomic analyses on stool samples to identify microbes that were excluded in risperidone-treated animals but remained present in controls. We identified multiple taxa including Limosilactobacillus reuteri as a candidate for further study. Oral supplementation with L. reuteri protected against risperidone-induced weight gain (RIWG) and was dependent on cellular production of a specialized metabolite, reutericyclin. Further, synthetic reutericyclin was sufficient to mitigate RIWG. Both synthetic reutericyclin and L. reuteri restored energy balance in the presence of risperidone to mitigate excess weight gain and induce shifts in the microbiome associated with leanness. In total, our results identify reutericyclin production by L. reuteri as a potential probiotic to restore energy balance induced by risperidone and to promote leanness.
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Affiliation(s)
- Fatima A. Aboulalazm
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Alexis B. Kazen
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Orlando deLeon
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Susanne Müller
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Fatima L. Saravia
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
| | | | - Matthew A. Hadiono
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Robert F. Keyes
- Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA
- Program in Chemical Biology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Brian C. Smith
- Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA
- Program in Chemical Biology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Stephanie L. Kellogg
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Justin L. Grobe
- Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
- Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI, USA
- Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin, Milwaukee, WI, USA
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Tammy L. Kindel
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - John R. Kirby
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA
- Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI, USA
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5
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Budzinski L, Kang GU, Riedel R, Sempert T, Lietz L, Maier R, Büttner J, Bochow B, Tordai MT, Shah A, Abbas A, Momtaz T, Krause JL, Kempkens R, Lehman K, Heinz GA, Benken AE, Bartsch S, Necke K, Hoffmann U, Mashreghi MF, Biesen R, Kallinich T, Alexander T, Jessen B, Weidinger C, Siegmund B, Radbruch A, Schirbel A, Moser B, Chang HD. Single-cell microbiota phenotyping reveals distinct disease and therapy-associated signatures in Crohn's disease. Gut Microbes 2025; 17:2452250. [PMID: 39815413 PMCID: PMC11740678 DOI: 10.1080/19490976.2025.2452250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 12/20/2024] [Accepted: 01/07/2025] [Indexed: 01/18/2025] Open
Abstract
IgA-coated fractions of the intestinal microbiota of Crohn's disease (CD) patients have been shown to contain taxa that hallmark the compositional dysbiosis in CD microbiomes. However, the correlation between other cellular properties of intestinal bacteria and disease has not been explored further, especially for features that are not directly driven by the host immune-system, e.g. the expression of surface sugars by bacteria. By sorting and sequencing IgA-coated and lectin-stained fractions from CD patients microbiota and healthy controls, we found that lectin-stained bacteria were distinct from IgA-coated bacteria, but still displayed specific differences between CD and healthy controls. To exploit the discriminatory potential of both, immunoglobulin coated bacteria and the altered surface sugar expression of bacteria in CD, we developed a multiplexed single cell-based analysis approach for intestinal microbiota. By multi-parameter microbiota flow cytometry (mMFC) we characterized the intestinal microbiota of 55 CD patients and 44 healthy controls for 11-parameters in total, comprising host-immunoglobulin coating and the presence of distinct surface sugar moieties. The data were analyzed by machine-learning to assess disease-specific marker patterns in the microbiota phenotype. mMFC captured detailed characteristics of CD microbiota and identified patterns to classify CD patients. In addition, we identified phenotypic signatures in the CD microbiota which not only reflected remission after 6 weeks of anti-TNF treatment, but were also able to predict remission before the start of an adalimumab treatment course in a pilot study. We here present the proof-of-concept demonstrating that multi-parameter single-cell bacterial phenotyping by mMFC could be a novel tool with high translational potential to expand current microbiome investigations by phenotyping of bacteria to identify disease- and therapy-associated cellular alterations and to reveal novel target properties of bacteria for functional assays and therapeutic approaches.
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Affiliation(s)
- Lisa Budzinski
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
- Department for Cytometry, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany
| | - Gi-Ung Kang
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
| | - René Riedel
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
- Bioinformatics and Computational Biology, Department of Cardiology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Toni Sempert
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
| | - Leonie Lietz
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
- Department for Cytometry, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany
| | - René Maier
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
| | - Janine Büttner
- Department of Hepatology and Gastroenterology, Campus Charité Mitte, Charité, Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Bettina Bochow
- Department of Hepatology and Gastroenterology, Campus Charité Mitte, Charité, Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Marcell T. Tordai
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Aayushi Shah
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
- Department for Cytometry, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany
| | - Amro Abbas
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
| | - Tanisha Momtaz
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
- School of Pharmacy, BRAC University, Dhaka, Bangladesh
| | - Jannike L. Krause
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
| | - Robin Kempkens
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
| | - Katrin Lehman
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
| | - Gitta A. Heinz
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
| | - Anne E. Benken
- Department of Rheumatology, Campus Charité Mitte, Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Stefanie Bartsch
- Department of Paediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Campus Virchow, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Kathleen Necke
- Department of Paediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Campus Virchow, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Ute Hoffmann
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
| | - Mir-Farzin Mashreghi
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
| | - Robert Biesen
- Department of Rheumatology, Campus Charité Mitte, Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Tilmann Kallinich
- Department of Paediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Campus Virchow, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Tobias Alexander
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
- Department of Rheumatology, Campus Charité Mitte, Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Bosse Jessen
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Carl Weidinger
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Britta Siegmund
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- BIH Charité Clinician Scientist Program
| | - Andreas Radbruch
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
| | - Anja Schirbel
- Department of Hepatology and Gastroenterology, Campus Charité Mitte, Charité, Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Benjamin Moser
- Department of Hepatology and Gastroenterology, Campus Charité Mitte, Charité, Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- DRK Kliniken Berlin, Clinic for internal medicine – Gastroenterology, Haematology and Oncology, Nephrology, Centre for chronic gastrointestinal inflammations, Berlin, Germany
| | - Hyun-Dong Chang
- German Rheumatology Research Centre Berlin – A Leibniz Institute, Berlin, Germany
- Department for Cytometry, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany
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Wang H, Han J, Zhang XA. Interplay of m6A RNA methylation and gut microbiota in modulating gut injury. Gut Microbes 2025; 17:2467213. [PMID: 39960310 PMCID: PMC11834532 DOI: 10.1080/19490976.2025.2467213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 12/12/2024] [Accepted: 02/10/2025] [Indexed: 02/20/2025] Open
Abstract
The gut microbiota undergoes continuous variations among individuals and across their lifespan, shaped by diverse factors encompassing diet, age, lifestyle choices, medication intake, and disease states. These microbial inhabitants play a pivotal role in orchestrating physiological metabolic pathways through the production of metabolites like bile acids, choline, short-chain fatty acids, and neurotransmitters, thereby establishing a dynamic "gut-organ axis" with the host. The intricate interplay between the gut microbiota and the host is indispensable for gut health, and RNA N6-methyladenosine modification, a pivotal epigenetic mark on RNA, emerges as a key player in this process. M6A modification, the most prevalent internal modification of eukaryotic RNA, has garnered significant attention in the realm of RNA epigenetics. Recent findings underscore its potential to influence gut microbiota diversity and intestinal barrier function by modulating host gene expression patterns. Conversely, the gut microbiota, through its impact on the epigenetic landscape of host cells, may indirectly regulate the recruitment and activity of RNA m6A-modifying enzymes. This review endeavors to delve into the biological functions of m6A modification and its consequences on intestinal injury and disease pathogenesis, elucidating the partial possible mechanisms by which the gut microbiota and its metabolites maintain host intestinal health and homeostasis. Furthermore, it also explores the intricate crosstalk between them in intestinal injury, offering a novel perspective that deepens our understanding of the mechanisms underlying intestinal diseases.
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Affiliation(s)
- Haixia Wang
- College of Exercise and Health, Shenyang Sport University, Shenyang, China
| | - Juanjuan Han
- College of Exercise and Health, Shenyang Sport University, Shenyang, China
| | - Xin-An Zhang
- College of Exercise and Health, Shenyang Sport University, Shenyang, China
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Du W, Zou ZP, Ye BC, Zhou Y. Gut microbiota and associated metabolites: key players in high-fat diet-induced chronic diseases. Gut Microbes 2025; 17:2494703. [PMID: 40260760 PMCID: PMC12026090 DOI: 10.1080/19490976.2025.2494703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/26/2025] [Accepted: 04/11/2025] [Indexed: 04/24/2025] Open
Abstract
Excessive intake of dietary fats is strongly associated with an increased risk of various chronic diseases, such as obesity, diabetes, hepatic metabolic disorders, cardiovascular disease, chronic intestinal inflammation, and certain cancers. A significant portion of the adverse effects of high-fat diet on disease risk is mediated through modifications in the gut microbiota. Specifically, high-fat diets are linked to reduced microbial diversity, an overgrowth of gram-negative bacteria, an elevated Firmicutes-to-Bacteroidetes ratio, and alterations at various taxonomic levels. These microbial alterations influence the intestinal metabolism of small molecules, which subsequently increases intestinal permeability, exacerbates inflammatory responses, disrupts metabolic functions, and impairs signal transduction pathways in the host. Consequently, diet-induced changes in the gut microbiota play a crucial role in the initiation and progression of chronic diseases. This review explores the relationship between high-fat diets and gut microbiota, highlighting their roles and underlying mechanisms in the development of chronic metabolic diseases. Additionally, we propose probiotic interventions may serve as a promising adjunctive therapy to counteract the negative effects of high-fat diet-induced alterations in gut microbiota composition.
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Affiliation(s)
- Wei Du
- Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Zhen-Ping Zou
- Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Bang-Ce Ye
- Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Ying Zhou
- Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
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8
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Zhang Y, Mo C, Ai P, He X, Xiao Q, Yang X. Pharmacomicrobiomics: a new field contributing to optimizing drug therapy in Parkinson's disease. Gut Microbes 2025; 17:2454937. [PMID: 39875349 PMCID: PMC11776486 DOI: 10.1080/19490976.2025.2454937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 11/19/2024] [Accepted: 01/13/2025] [Indexed: 01/30/2025] Open
Abstract
Gut microbiota, which act as a determinant of pharmacokinetics, have long been overlooked. In recent years, a growing body of evidence indicates that the gut microbiota influence drug metabolism and efficacy. Conversely, drugs also exert a substantial influence on the function and composition of the gut microbiota. Pharmacomicrobiomics, an emerging field focusing on the interplay of drugs and gut microbiota, provides a potential foundation for making certain advances in personalized medicine. Understanding the communication between gut microbiota and antiparkinsonian drugs is critical for precise treatment of Parkinson's disease. Here, we provide a historical overview of the interplay between gut microbiota and antiparkinsonian drugs. Moreover, we discuss potential mechanistic insights into the complex associations between gut microbiota and drug metabolism. In addition, we also draw attention to microbiota-based biomarkers for predicting antiparkinsonian drug efficacy and examine current state-of-the-art knowledge of microbiota-based strategies to optimize drug therapy in Parkinson's disease.
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Affiliation(s)
- Yi Zhang
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chengjun Mo
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Penghui Ai
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoqin He
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qin Xiao
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaodong Yang
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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9
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Li XL, Megdadi M, Quadri HS. Interaction between gut virome and microbiota on inflammatory bowel disease. World J Methodol 2025; 15:100332. [DOI: 10.5662/wjm.v15.i3.100332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 12/31/2024] [Accepted: 01/15/2025] [Indexed: 03/06/2025] Open
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic condition marked by recurring gastrointestinal inflammation. While immune, genetic, and environmental factors are well-studied, the gut virome has received less attention. This editorial highlights the work which investigates the gut virome’s role in IBD and its interactions with the bacterial microbiome and host immune system. The gut virome consists of bacteriophages, eukaryotic viruses, and endogenous retroviruses. Among these, Caudovirales bacteriophages are predominant and influence bacterial communities via lysogenic and lytic cycles. Eukaryotic viruses infect host cells directly, while endogenous retroviruses impact gene regulation and immune responses. In IBD, the virome shows distinct alterations, including an increased abundance of Caudovirales phages and reduced Microviridae diversity, suggesting a pro-inflammatory viral environment. Dysbiosis, chronic inflammation, and aberrant immune responses contribute to these changes by disrupting microbial communities and modifying virome composition. Phages affect bacterial dynamics through lysis, lysogeny, and horizontal gene transfer, shaping microbial adaptability and resilience. Understanding these interactions is crucial for identifying novel therapeutic targets and restoring microbial balance in IBD.
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Affiliation(s)
- Xiao-Long Li
- Department of Surgery, Ascension St Agnes Hospital, Baltimore, MD 21009, United States
| | - Mueen Megdadi
- Department of Surgery, Ascension St Agnes Hospital, Baltimore, MD 21009, United States
| | - Humair S Quadri
- Department of Surgery, Ascension St Agnes Hospital, Baltimore, MD 21009, United States
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10
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Kulkarni H, Gaikwad AB. The mitochondria-gut microbiota crosstalk - A novel frontier in cardiovascular diseases. Eur J Pharmacol 2025; 998:177562. [PMID: 40157703 DOI: 10.1016/j.ejphar.2025.177562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Revised: 03/06/2025] [Accepted: 03/26/2025] [Indexed: 04/01/2025]
Abstract
Cardiovascular diseases (CVDs), including hypertension, atherosclerosis, and cardiomyopathy among others, remain the leading cause of global morbidity and mortality. Despite advances in treatment, the complex pathophysiology of CVDs necessitates innovative approaches to improve patient outcomes. Recent research has uncovered a dynamic interplay between mitochondria and gut microbiota, fundamentally altering our understanding of cardiovascular health. However, while existing studies have primarily focused on individual components of this axis, this review examines the bidirectional communication between these biological systems and their collective impact on cardiovascular health. Mitochondria, serving as cellular powerhouses, are crucial for maintaining cardiovascular homeostasis through oxidative phosphorylation (OXPHOS), calcium regulation, and redox balance. Simultaneously, the gut microbiota influences cardiovascular function through metabolite production, barrier integrity maintenance, and immune system modulation. The mitochondria-gut microbiota axis operates through various molecular mechanisms, including microbial metabolites such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFA), and secondary bile acids, which directly influence mitochondrial function. Conversely, mitochondrial stress signals and damage-associated molecular patterns (DAMPs) affect gut microbial communities and barrier function. Key signalling pathways, including AMP-activated protein kinase (AMPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and the silent information regulator 1-peroxisome proliferator-activated receptor gamma coactivator 1-alpha (SIRT1-PGC-1α) axis, integrate these interactions, highlighting their role in CVD pathogenesis. Understanding these interactions has revealed promising therapeutic targets, suggesting new therapies aimed at both mitochondrial function and gut microbiota composition. Thus, this review provides a comprehensive framework for leveraging the mitochondria-gut microbiota axis in providing newer therapeutics for CVDs by targeting the AMPK/SIRT-1/PGC-1α/NF-κB signalling.
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Affiliation(s)
- Hrushikesh Kulkarni
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Vidya Vihar, Pilani, Rajasthan 333031, India
| | - Anil Bhanudas Gaikwad
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Vidya Vihar, Pilani, Rajasthan 333031, India.
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11
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Yang S, Liu X, Chen Y, Wang X, Zhang Z, Wang L. NNSFMDA: Lightweight Transformer Model with Bounded Nuclear Norm Minimization for Microbe-Drug Association Prediction. J Mol Biol 2025; 437:169086. [PMID: 40139309 DOI: 10.1016/j.jmb.2025.169086] [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: 02/21/2025] [Accepted: 03/07/2025] [Indexed: 03/29/2025]
Abstract
Identifying potential connections between microbe-drug pairs play an important role in drug discovery and clinical treatment. Techniques like graph neural networks effectively derive accurate node representations from sparse topologies,however, they struggle with over-smoothing and over-compression, and their interpretability is relatively poor. Conversely, mathematical methods with low-rank approximations are interpretable but often get trapped in local optima. To address these issues, we propose a new prediction model named NNSFMDA, in which, the bounded nuclear norm minimization and the simplified transformer were combined to infer possible drug-microbe associations. In NNSFMDA, we first constructed a heterogeneous microbe-drug network by integrating multiple microbe and drug similarity metrics, according to which, we subsequently transformed the prediction problem to a matrix filling problem, and then, iteratively approximated the matrix by minimizing the number of bounded nuclear norm. Finally, based on the newly-filled matrix, we introduced a simplified transformer to estimate possible scores of microbe-drug pairs. Results showed that NNSFMDA could achieve reliable AUC value of 0.98, which outperformed existing state-of-the-art competitive methods. In the experimental section, ablation experiments and modular analyses further demonstrate the superiority of the model, and case studies of microbe-drug associations confirm the validity of the model. These tests have all highlighted the potential of the NNSFMDA to predict latent microbe-drug associations in the future.
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Affiliation(s)
- Shuyuan Yang
- School of Mathematics, Changsha University, Changsha 410022, China; Big Data Innovation and Entrepreneurship Education Center of Hunan Province, Changsha University, Changsha 410022, China
| | - Xin Liu
- School of Computer Science & Computer Engineering, Changsha University, Changsha 410022, China; Big Data Innovation and Entrepreneurship Education Center of Hunan Province, Changsha University, Changsha 410022, China.
| | - Yiming Chen
- School of Computer Science & Computer Engineering, Changsha University, Changsha 410022, China; Big Data Innovation and Entrepreneurship Education Center of Hunan Province, Changsha University, Changsha 410022, China
| | - Xiangyi Wang
- School of Artificial Intelligence, The University of New South Wales, Sydney, Australia
| | - Zhen Zhang
- School of Computer Science & Computer Engineering, Changsha University, Changsha 410022, China; Big Data Innovation and Entrepreneurship Education Center of Hunan Province, Changsha University, Changsha 410022, China
| | - Lei Wang
- School of Computer Science & Computer Engineering, Changsha University, Changsha 410022, China; Big Data Innovation and Entrepreneurship Education Center of Hunan Province, Changsha University, Changsha 410022, China
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12
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Deleu S, Sabino J. Personalized Dietary Approaches to Optimizing Intestinal Microbial Health and Homeostasis. Gastroenterol Clin North Am 2025; 54:317-331. [PMID: 40348490 DOI: 10.1016/j.gtc.2024.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Diet has a profound impact in human health, which is partly driven by changes in the intestinal microbiota. Several associations between dietary intake and the intestinal microbiota composition and function have been described. Namely, the Mediterranean diet is associated with beneficial bacteria, while the intake of ultraprocessed foods is linked to dysbiosis. It is, therefore, very tempting to tailor dietary approaches to the individual needs of the microbiota; however, high-quality prospective data are lacking. Provisionally, a diet rich in fruits and vegetables and low in ultraprocessed foods is recommended to improve the intestinal microbiota composition and function.
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Affiliation(s)
- Sara Deleu
- Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, Rome 00168, Italy
| | - João Sabino
- Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
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13
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Ma G, Yang P, Lu T, Deng X, Meng L, Xie H, Zhou J, Xiao X, Tang X. Comparative analysis of oral, placental, and gut microbiota characteristics, functional features and microbial networks in healthy pregnant women. J Reprod Immunol 2025; 169:104535. [PMID: 40315739 DOI: 10.1016/j.jri.2025.104535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 04/14/2025] [Accepted: 04/27/2025] [Indexed: 05/04/2025]
Abstract
AIM Most studies on pregnant women focus on analyzing individual microbial species at specific body sites. This study aims to explore the characteristics, functions, and microbial networks of the oral, placental, and gut microbiota in healthy pregnant women. METHODS A total of 23 healthy pregnant women were enrolled in this study. We analyzed the microbial composition, functional profiles, and microbial networks of the oral, placental, and gut microbiota using 16S rRNA gene sequencing. RESULTS Our findings revealed significant differences in microbial composition across these three sites. The placental microbiota contained a relatively high proportion of low-abundance microorganisms, which were more diverse and evenly distributed compared to the gut and oral microbiota. The microbial composition at each site displayed distinct characteristics, likely influenced by environmental, physiological, and biological factors. The placental microbiota exhibited a complex network of tightly interconnected genera, whereas the gut microbiota showed sparser connections, with fewer closely related genera compared to the placental and oral microbiota. Functional differences were also observed among the three microbiota, with each playing a unique role in maintaining host health and metabolic balance. While the oral and gut microbiota shared functional similarities, the placental microbiota exhibited distinct functional characteristics. CONCLUSIONS This study provides valuable insights into the microbial communities of healthy pregnant women, offering important data for microbiological research during pregnancy and laying the foundation for future investigations into the roles of these microbial communities in maternal health.
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Affiliation(s)
- Guangyu Ma
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Ping Yang
- Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong province, China
| | - Tong Lu
- Department of Otolaryngology, Shenzhen Long Hua District Central Hospital, Shenzhen, China
| | - Xinyi Deng
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Lulu Meng
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Haishan Xie
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Juan Zhou
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Xiaomin Xiao
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
| | - Xiaomei Tang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
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14
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Lei Y, Deng Y, Xia R, Xie B, Yang Z, Xi S, Chen P, Tao R. Full-length 16S rRNA-based exploration of body site-specific bacterial signatures for origin determination and individual identification. Forensic Sci Int 2025; 371:112475. [PMID: 40286757 DOI: 10.1016/j.forsciint.2025.112475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 04/13/2025] [Accepted: 04/18/2025] [Indexed: 04/29/2025]
Abstract
When the available human-derived information at a crime scene is limited, it poses challenges in determining the origin of the biological materials and identifying their donors. In this context, microorganisms have gradually emerged as a valuable complementary tool. Nowadays, the application of third-generation sequencing technology for full-length 16S rRNA sequencing to explore the specific bacterial biomarkers in various biological materials holds significant research and practical value. In this study, we performed full-length 16S rRNA gene sequencing on sterile swabs from palmar skin, oral mucosa, and nasal cavity using the PacBio single-molecule real-time sequencing (SMRT) platform. Alongside identifying specific bacterial biomarkers for these biological materials from different body sites, the study also preliminarily explored the specific bacterial taxa in 19 individuals at the phylum, genus, and species levels. The results showed that the palmar skin bacteria primarily consist of Cutibacterium, Staphylococcus, and Streptococcus, the oral mucosal bacteria are dominated by Streptococcus, Neisseria, and Haemophilus, while the dominant bacteria in nasal cavity are Staphylococcus and Cutibacterium. Beta diversity analysis revealed significant differences in the bacterial community composition across the three origins of biological materials. Furthermore, classification models based on the bacterial species were constructed using the Random Forest, XGBoost, and KNN algorithms. The results showed that both Random Forest and XGBoost models achieved an accuracy of 97 %, significantly outperforming the KNN model (79 %). The prediction accuracy at the OTU level was comparable to that at the species level. In addition, bacterial community differences between individuals were observed at both the genus and species levels. Overall, this study further explores the potential of classification prediction methods based on bacterial features for distinguishing the body site origins of different biological materials and enabling individual traceability, thereby providing valuable data to support the application of microbiological techniques in forensic practice.
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Affiliation(s)
- Yinlei Lei
- Key Laboratory of Cell Engineering of Guizhou Province, Clinical Stem Cell Research Institute, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563099, China; Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Sciences, Key Laboratory of Forensic Science, Ministry of Justice, Shanghai 200063, China
| | - Yu Deng
- Key Laboratory of Cell Engineering of Guizhou Province, Clinical Stem Cell Research Institute, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563099, China; Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Sciences, Key Laboratory of Forensic Science, Ministry of Justice, Shanghai 200063, China
| | - Ruocheng Xia
- Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Sciences, Key Laboratory of Forensic Science, Ministry of Justice, Shanghai 200063, China
| | - Baoyan Xie
- Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Sciences, Key Laboratory of Forensic Science, Ministry of Justice, Shanghai 200063, China
| | - Zhenchen Yang
- Criminal Science and Technology Research Institute, Fengxian Branch of Shanghai Municipal Public Security Bureau, Shanghai 201499, China
| | - Shuangyun Xi
- School of Forensic Medicine, Zunyi Medical University, Zunyi, Guizhou, China
| | - Pengyu Chen
- Key Laboratory of Cell Engineering of Guizhou Province, Clinical Stem Cell Research Institute, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563099, China.
| | - Ruiyang Tao
- Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Sciences, Key Laboratory of Forensic Science, Ministry of Justice, Shanghai 200063, China.
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15
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Støy S, Schnabl B. Role of Intestinal Microbiome in Potentiating Inflammation and Predicting Outcomes in Alcohol-Associated Cirrhosis. Gastroenterol Clin North Am 2025; 54:453-467. [PMID: 40348498 PMCID: PMC12066832 DOI: 10.1016/j.gtc.2024.12.001] [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] [Indexed: 05/14/2025]
Abstract
In patients with alcohol-associated cirrhosis, the intestinal microbiome composition is disturbed with a loss of beneficial functions and an increase in pathobionts. These changes are associated with disease severity and decompensation, due in part to the exacerbation of liver inflammation by an altered microbiome. Microbes or their antigens may translocate to the liver to potentiate the activation of immune cells and thereby contribute to inflammatory injury. Moreover, microbes may aggravate liver disease through the production of toxins or metabolites, via the effects on bile acids or the intestinal immune system.
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Affiliation(s)
- Sidsel Støy
- Department of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA.
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16
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Ejiugwo MA, Gawenda JV, Janis AD, McNamara DA, O'Donnell ST, Browne S. Understanding the Impact of Ostomy Dejecta Constituents on Peristomal Skin Health and Models for Its Characterisation. Int Wound J 2025; 22:e70514. [PMID: 40400213 PMCID: PMC12095849 DOI: 10.1111/iwj.70514] [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: 01/14/2025] [Revised: 03/27/2025] [Accepted: 04/02/2025] [Indexed: 05/23/2025] Open
Abstract
An ostomy, or stoma, is a surgically created percutaneous aperture from a hollow organ (e.g., small intestine) to the body's surface. Physicians may recommend an ostomy as a temporary or permanent solution to a range of disorders of the gastrointestinal tract, with up to 130 000 ostomies performed annually in the United States. An ostomy facilitates the expulsion of waste products, termed dejecta and circumvents the compromised organs. While an ostomy can be a lifesaving treatment, it is a disruption of regular digestive flow and has a number of associated complications including hernia, prolapse and necrosis. The most commonly observed complications are peristomal skin complications (PSCs), attributed to the leakage of dejecta onto the peristomal skin or the skin directly surrounding the stoma. Despite the prevalence of PSCs, little is known about the precise etiological factors that play a role in PSC formation. This review discusses the constituents of dejecta and their possible roles in PSC formation. Additionally, we identify a number of in vitro and in vivo skin models that could be used to study PSCs. Identification of the components of dejecta and understanding their interaction with skin models can facilitate the development of interventions to treat and prevent PSCs.
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Affiliation(s)
- Mirella A. Ejiugwo
- Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative MedicineRoyal College of Surgeons in Ireland (RCSI)DublinIreland
| | - Julie V. Gawenda
- Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative MedicineRoyal College of Surgeons in Ireland (RCSI)DublinIreland
| | | | | | - Sinéad T. O'Donnell
- Department of Clinical MicrobiologyRoyal College of Surgeons in Ireland (RCSI)DublinIreland
- Department of Clinical MicrobiologyBeaumont HospitalDublinIreland
| | - Shane Browne
- Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative MedicineRoyal College of Surgeons in Ireland (RCSI)DublinIreland
- CÚRAM, Centre for Research in Medical DevicesNational University of IrelandGalwayIreland
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17
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Garcia-Morena D, Fernandez-Cantos MV, Escalera SL, Lok J, Iannone V, Cancellieri P, Maathuis W, Panagiotou G, Aranzamendi C, Aidy SE, Kolehmainen M, El-Nezami H, Wellejus A, Kuipers OP. In Vitro Influence of Specific Bacteroidales Strains on Gut and Liver Health Related to Metabolic Dysfunction-Associated Fatty Liver Disease. Probiotics Antimicrob Proteins 2025; 17:1498-1512. [PMID: 38319537 PMCID: PMC12055940 DOI: 10.1007/s12602-024-10219-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/17/2024] [Indexed: 02/07/2024]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a major health risk and a serious worldwide issue. MAFLD typically arises from aberrant lipid metabolism, insulin resistance, oxidative stress, and inflammation. However, subjacent causes are multifactorial. The gut has been proposed as a major factor in health and disease, and over the last decade, bacterial strains with potentially beneficial effects on the host have been identified. In vitro cell models have been commonly used as an early step before in vivo drug assessment and can confer complementary advantages in gut and liver health research. In this study, several selected strains of the order Bacteroidales were used in a three-cell line in vitro analysis (HT-29, Caco-2, and HepG2 cell lines) to investigate their potential as new-generation probiotics and microbiota therapeutics. Antimicrobial activity, a potentially useful trait, was studied, and the results showed that Bacteroidales can be a source of either wide- or narrow-spectrum antimicrobials targeting other closely related strains. Moreover, Bacteroides sp. 4_1_36 induced a significant decrease in gut permeability, as evidenced by the high TEER values in the Caco-2 monolayer assay, as well as a reduction in free fatty acid accumulation and improved fatty acid clearance in a steatosis HepG2 model. These results suggest that Bacteroidales may spearhead the next generation of probiotics to prevent or diminish MAFLD.
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Affiliation(s)
- Diego Garcia-Morena
- Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands
| | - Maria Victoria Fernandez-Cantos
- Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands
| | - Silvia Lopez Escalera
- Chr. Hansen A/S, Bøge Allé 10-12, 2970, Hørsholm, Denmark
- Friedrich-Schiller Universität Jena, Fakultät für Biowissenschaften, 18K, 07743, Bachstraβe, Germany
| | - Johnson Lok
- School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200, Kuopio, Finland
| | - Valeria Iannone
- School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200, Kuopio, Finland
| | - Pierluca Cancellieri
- Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands
| | - Willem Maathuis
- Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands
| | - Gianni Panagiotou
- Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), 07745, Jena, Germany
- Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, China
- Faculty of Biological Sciences, Friedrich Schiller University, 07745, Jena, Germany
| | - Carmen Aranzamendi
- Groningen Biomolecular Sciences and Biotechnology Institute, Host-Microbe Metabolic Interactions, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands
| | - Sahar El Aidy
- Groningen Biomolecular Sciences and Biotechnology Institute, Host-Microbe Metabolic Interactions, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands
| | - Marjukka Kolehmainen
- School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200, Kuopio, Finland
| | - Hani El-Nezami
- Molecular and Cell Biology Division, School of Biological Sciences, University of Hong Kong, Pok Fu Lam, Hong Kong SAR
| | - Anja Wellejus
- Chr. Hansen A/S, Bøge Allé 10-12, 2970, Hørsholm, Denmark
| | - Oscar P Kuipers
- Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
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18
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Chen Y, Lei Z, Gu D, Zhao H, Yu R, He Q, Xu M, Du H. Gut microbiota: A potential enhancing factor for the therapeutic efficacy of bioactive compounds in herbal medicines. Fitoterapia 2025; 183:106570. [PMID: 40288589 DOI: 10.1016/j.fitote.2025.106570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 04/14/2025] [Accepted: 04/24/2025] [Indexed: 04/29/2025]
Abstract
The therapeutic efficacy of herbal medicines (HMs) is often compromised by the low bioavailability of their bioactive compounds. However, emerging evidence highlights the crucial role of gut microbiota in enhancing their effectiveness. This review summarizes gut microbiota-mediated metabolism of key herbal components, including terpenoids, flavonoids, alkaloids, and quinones. Particular emphasis is placed on the diverse gut microbiota, enzymes, and metabolites that participate in the biotransformation pathways of these active components of HMs. Exploring the metabolism between the gut microbiota and bioactive compounds gives a better understanding of HMs with multiple components against multiple targets, complex mechanisms of action, and diverse physiological activities. This review underscores the critical importance of gut microbiota in modulating and potentially enhancing the pharmacological effects of HMs, which offers new insights into gut microbiota-mediated transformation pathways and molecular mechanisms of bioactive compounds and deepens the understanding of the therapeutic effects of HMs. Moreover, it suggests new research directions for studying HMs based on gut microbiota-mediated biotransformation.
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Affiliation(s)
- Yu Chen
- Department of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Ziqin Lei
- Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu 610014, Sichuan, China
| | - Deying Gu
- Department of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Huiling Zhao
- Department of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Rong Yu
- Department of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Qin He
- Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu 610014, Sichuan, China
| | - Min Xu
- Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu 610014, Sichuan, China
| | - Huan Du
- Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu 610014, Sichuan, China.
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19
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Rodríguez Del Río Á, Scheu S, Rillig MC. Soil microbial responses to multiple global change factors as assessed by metagenomics. Nat Commun 2025; 16:5058. [PMID: 40447574 DOI: 10.1038/s41467-025-60390-4] [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: 07/10/2024] [Accepted: 05/22/2025] [Indexed: 06/02/2025] Open
Abstract
Anthropogenic activities impose multiple concurrent pressures on soils globally, but responses of soil microbes to multiple global change factors are poorly understood. Here, we apply 10 treatments (warming, drought, nitrogen deposition, salinity, heavy metal, microplastics, antibiotics, fungicides, herbicides and insecticides) individually and in combinations of 8 factors to soil samples, and monitor their bacterial and viral composition by metagenomic analysis. We recover 742 mostly unknown bacterial and 1865 viral Metagenome-Assembled Genomes (MAGs), and leverage them to describe microbial populations under different treatment conditions. The application of multiple factors selects for prokaryotic and viral communities different from any individual factor, favouring the proliferation of potentially pathogenic mycobacteria and novel phages, which apparently play a role in shaping prokaryote communities. We also build a 25 M gene catalog to show that multiple factors select for metabolically diverse, sessile and non-biofilm-forming bacteria with a high load of antibiotic resistance genes. Finally, we show that novel genes are relevant for understanding microbial response to global change. Our study indicates that multiple factors impose selective pressures on soil prokaryotes and viruses not observed at the individual factor level, and emphasizes the need of studying the effect of concurrent global change treatments.
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Affiliation(s)
| | - Stefan Scheu
- JFB Institute of Zoology and Anthropology, University of Göttingen, Göttingen, Germany
- Centre of Biodiversity and Sustainable Land Use, University of Göttingen, Göttingen, Germany
| | - Matthias C Rillig
- Institute of Biology, Freie Universität Berlin, Berlin, Germany
- Berlin-Brandenburg Institute of Advanced Biodiversity Research (BBIB), Berlin, Germany
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20
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Komatsu S, Tamura Y, Takagi K, Yamazaki S, Matsumura A, Kubota K, Narita N, Matsumiya T, Sawada K, Mikami T, Nakaji S, Kobayashi W. Association between oral bacterial species and halitosis: findings from a study of a community-based Japanese population. J Breath Res 2025; 19:036010. [PMID: 40403744 DOI: 10.1088/1752-7163/addc0c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 05/22/2025] [Indexed: 05/24/2025]
Abstract
Halitosis is known to be associated with oral bacteria; however, its specific relationship with particular bacterial species within the oral microbiota remains uncertain. Our objective was to identify oral bacterial species associated with volatile sulfur compound (VSC) production that contribute to halitosis in a community-based Japanese population. This study included 1018 participants. Tongue plaque samples were collected and the oral microbiome was analyzed via 16S rDNA amplicon sequencing. Participants with VSC levels greater than 250 ppb were categorized as having oral malodor. Linear discriminant analysis effect size was used to compare bacterial compositions between participants with and without halitosis. In this study, we identified 37 bacterial genera in tongue plaque samples. Significant differences in bacterial composition were found between the malodor and control groups.Porphyromonas, Fusobacterium, andSolobacteriumwere more abundant in the malodor group, whereasStreptococcusandRothiawere more prevalent in the control group. Multiple regression analysis further revealed thatPorphyromonasandSolobacteriumabundances were positively correlated with oral malodor. We found that halitosis in this Japanese population is associated primarily with pathogenic periodontal bacteria (members of the red and orange complexes) andSolobacterium moorei. The bacterial community composition of individuals with halitosis differs significantly from that of healthy individuals, emphasizing the role of specific bacterial species in oral malodor development. These findings increase our understanding of the microbial basis of halitosis and suggest that targetingSolobacterium, along with treating periodontal disease, may be effective in combating halitosis.
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Affiliation(s)
- Shotaro Komatsu
- Department of Oral and Maxillofacial Surgery, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan
| | - Yoshihiro Tamura
- Department of Oral and Maxillofacial Surgery, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan
| | - Koki Takagi
- Department of Oral and Maxillofacial Surgery, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan
| | - Shunya Yamazaki
- Department of Oral and Maxillofacial Surgery, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan
| | - Akihiro Matsumura
- Department of Oral and Maxillofacial Surgery, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan
| | - Kosei Kubota
- Department of Oral and Maxillofacial Surgery, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan
| | - Norihiko Narita
- Department of Oral and Maxillofacial Surgery, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan
| | - Tomoh Matsumiya
- Department of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Sciences, Hirosaki City, Aomori, Japan
| | - Kaori Sawada
- Department of Preemptive Medicine, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan
| | - Tatsuya Mikami
- Department of Preemptive Medicine, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan
| | - Shigeyuki Nakaji
- Department of Preemptive Medicine, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan
| | - Wataru Kobayashi
- Department of Oral and Maxillofacial Surgery, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan
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21
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Koldaş SS, Sezerman OU, Timuçin E. Exploring the role of microbiome in cystic fibrosis clinical outcomes through a mediation analysis. mSystems 2025:e0019625. [PMID: 40434093 DOI: 10.1128/msystems.00196-25] [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: 02/08/2025] [Accepted: 05/05/2025] [Indexed: 05/29/2025] Open
Abstract
Human microbiome plays a crucial role in host health and disease by mediating the impact of environmental factors on clinical outcomes. Mediation analysis is a valuable tool for dissecting these complex relationships. However, existing approaches are primarily designed for cross-sectional studies. Modern clinical research increasingly utilizes long follow-up periods, leading to complex data structures, particularly in metagenomic studies. To address this limitation, we introduce a novel mediation framework based on structural equation modeling that leverages linear mixed-effects models using penalized quasi-likelihood estimation with a debiased lasso. We applied this framework to a 16S rRNA sputum microbiome data set collected from patients with cystic fibrosis over 10 years to investigate the mediating role of the microbiome in the relationship between clinical states, disease aggressiveness phenotypes, and lung function. We identified richness as a key mediator of lung function. Specifically, Streptococcus was found to be significantly associated with mediating the decline in lung function on treatment compared to exacerbation, while Gemella was associated with the decline in lung function on recovery. This approach offers a powerful new tool for understanding the complex interplay between microbiome and clinical outcomes in longitudinal studies, facilitating targeted microbiome-based interventions. IMPORTANCE Understanding the mechanisms by which the microbiome influences clinical outcomes is paramount for realizing the full potential of microbiome-based medicine, including diagnostics and therapeutics. Identifying specific microbial mediators not only reveals potential targets for novel therapies and drug repurposing but also offers a more precise approach to patient stratification and personalized interventions. While traditional mediation analyses are ill-equipped to address the complexities of longitudinal metagenomic data, our framework directly addresses this gap, enabling robust investigation of these increasingly common study designs. By applying this framework to a decade-long cystic fibrosis study, we have begun to unravel the intricate relationships between the sputum microbiome and lung function decline across different clinical states, yielding insights that were previously unknown.
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Affiliation(s)
- Seda Sevilay Koldaş
- Biostatistics and Bioinformatics, School of Health Science, Acıbadem Mehmet Ali Aydınlar University, , Istanbul, Turkey
| | - Osman Uğur Sezerman
- Biostatistics and Bioinformatics, School of Health Science, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey
| | - Emel Timuçin
- Molecular Biology and Genetics, Faculty of Science, Gebze Technical University, Kocaeli, Turkey
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22
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Ma C, Yang J, Fu XN, Luo JY, Liu P, Zeng XL, Li XY, Zhang SL, Zheng S. Microbial characteristics of gut microbiome dysbiosis in patients with chronic liver disease. World J Hepatol 2025; 17:106124. [DOI: 10.4254/wjh.v17.i5.106124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Revised: 03/28/2025] [Accepted: 04/24/2025] [Indexed: 05/27/2025] Open
Abstract
BACKGROUND In this study, we are committed to exploring the characteristics of the gut microbiome in three different stages of chronic liver disease (CLD): Chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma (HCC).
AIM To delineate the gut microbiota traits in individuals with chronic liver ailments (chronic hepatitis B, cirrhosis, HCC), scrutinizes microbiome alterations during the progression of these diseases, and assesses microbiome disparities among various Child-Pugh categories in cirrhosis sufferers.
METHODS A cohort of 60 CLD patients from the Third People’s Hospital of Yunnan Province were recruited from February to August 2023, together with 37 healthy counterparts. Employing 16SrDNA high-throughput sequencing, we evaluated the diversity and composition of the gut microbiota.
RESULTS Compared to healthy subjects, patients exhibited a reduced presence of Firmicutes and a corresponding decline in butyrate-producing genera. In contrast, an upsurge in Proteobacteria was observed in the diseased cohorts, particularly an increase in Enterobacteriaceae that intensified with the disease's progression. At the genus level, the occurrence of Escherichia_Shigella, Parabacteroides, Streptococcus, Klebsiella, and Enterococcus was higher, with Escherichia_Shigella numbers augmenting as the disease advanced. Furthermore, in cirrhosis patients, an increase in Proteobacteria was noted as liver reserve diminished, alongside a decrease in Ruminococcaceae and Bacteroidaceae.
CONCLUSION The reduced abundance of short-chain fatty acid-producing bacteria in the intestine, alongside the increased abundance of gram-negative bacteria such as Escherichia_Shigella and Parabacteroides, may promote the progression of CLD.
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Affiliation(s)
- Chi Ma
- Department of Gastroenterology, The Second Affiliated Hospital of Dali University, Kunming 650011, Yunnan Province, China
| | - Juan Yang
- Department of Gastroenterology, The Third People’s Hospital of Yunnan Province, Kunming 650011, Yunnan Province, China
| | - Xin-Nian Fu
- Department of Gastroenterology, The Second Affiliated Hospital of Dali University, Kunming 650011, Yunnan Province, China
| | - Jiang-Yan Luo
- Department of Gastroenterology, The Second Affiliated Hospital of Dali University, Kunming 650011, Yunnan Province, China
| | - Pei Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Dali University, Kunming 650011, Yunnan Province, China
| | - Xue-Li Zeng
- Department of Gastroenterology, The Second Affiliated Hospital of Dali University, Kunming 650011, Yunnan Province, China
| | - Xin-Yi Li
- Department of Gastroenterology, The Second Affiliated Hospital of Dali University, Kunming 650011, Yunnan Province, China
| | - Shun-Ling Zhang
- Department of Gastroenterology, The Second Affiliated Hospital of Dali University, Kunming 650011, Yunnan Province, China
| | - Sheng Zheng
- Department of Gastroenterology, The Third People’s Hospital of Yunnan Province, Kunming 650011, Yunnan Province, China
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23
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Seira Curto J, Dominguez Martinez A, Perez Collell G, Barniol Simon E, Romero Ruiz M, Franco Bordés B, Sotillo Sotillo P, Villegas Hernandez S, Fernandez MR, Sanchez de Groot N. Exogenous prion-like proteins and their potential to trigger cognitive dysfunction. Mol Syst Biol 2025:10.1038/s44320-025-00114-4. [PMID: 40425815 DOI: 10.1038/s44320-025-00114-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 04/16/2025] [Accepted: 05/02/2025] [Indexed: 05/29/2025] Open
Abstract
The gut is exposed to a wide range of proteins, including ingested proteins and those produced by the resident microbiota. While ingested prion-like proteins can propagate across species, their implications for disease development remain largely unknown. Here, we apply a multidisciplinary approach to examine the relationship between the biophysical properties of exogenous prion-like proteins and the phenotypic consequences of ingesting them. Through computational analysis of gut bacterial proteins, we identified an enrichment of prion-like sequences in Helicobacter pylori. Based on these findings, we rationally designed a set of synthetic prion-like sequences that form amyloid fibrils, interfere with amyloid-beta-peptide aggregation, and trigger prion propagation when introduced in the yeast Sup35 model. When C. elegans were fed bacteria expressing these prion-like proteins, they lost associative memory and exhibited increased lipid oxidation. These data suggest a link between memory impairment, the conformational state of aggregates, and oxidative stress. Overall, this work supports gut microbiota as a reservoir of exogenous prion-like sequences, especially H. pylori, and the gut as an entry point for molecules capable of triggering cognitive dysfunction.
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Affiliation(s)
- Jofre Seira Curto
- Unitat de Bioquímica, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Adan Dominguez Martinez
- Unitat de Bioquímica, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
- Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
| | - Genis Perez Collell
- Unitat de Bioquímica, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Estrella Barniol Simon
- Unitat de Bioquímica, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Marina Romero Ruiz
- Unitat de Bioquímica, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Berta Franco Bordés
- Unitat de Bioquímica, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Paula Sotillo Sotillo
- Unitat de Bioquímica, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Sandra Villegas Hernandez
- Unitat de Bioquímica, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Maria Rosario Fernandez
- Unitat de Bioquímica, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain.
| | - Natalia Sanchez de Groot
- Unitat de Bioquímica, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain.
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24
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Doing G, Shanbhag P, Bell I, Cassidy S, Motakis E, Aiken E, Oh J, Adams MD. TEAL-Seq: targeted expression analysis sequencing. mSphere 2025; 10:e0098424. [PMID: 40261045 DOI: 10.1128/msphere.00984-24] [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: 11/25/2024] [Accepted: 03/27/2025] [Indexed: 04/24/2025] Open
Abstract
Metagenome sequencing enables the genetic characterization of complex microbial communities. However, determining the activity of isolates within a community presents several challenges, including the wide range of organismal and gene expression abundances, the presence of host RNA, and low microbial biomass at many sites. To address these limitations, we developed "targeted expression analysis sequencing" or TEAL-seq, enabling sensitive species-specific analyses of gene expression using highly multiplexed custom probe pools. For proof of concept, we targeted about 1,700 core and accessory genes of Staphylococcus aureus and S. epidermidis, two key species of the skin microbiome. Two targeting methods were applied to laboratory cultures and human nasal swab specimens. Both methods showed a high degree of specificity, with >90% reads on target, even in the presence of complex microbial or human background DNA/RNA. Targeting using molecular inversion probes demonstrated excellent correlation in inferred expression levels with bulk RNA-seq. Furthermore, we show that a linear pre-amplification step to increase the number of nucleic acids for analysis yielded consistent and predictable results when applied to complex samples and enabled profiling of expression from as little as 1 ng of total RNA. TEAL-seq is much less expensive than bulk metatranscriptomic profiling, enables detection across a greater dynamic range, and uses a strategy that is readily configurable for determining the transcriptional status of organisms in any microbial community.IMPORTANCEThe gene expression patterns of bacteria in microbial communities reflect their activity and interactions with other community members. Measuring gene expression in complex microbiome contexts is challenging, however, due to the large dynamic range of microbial abundances and transcript levels. Here we describe an approach to assessing gene expression for specific species of interest using highly multiplexed pools of targeting probes. We show that an isothermal amplification step enables the profiling of low biomass samples. TEAL-seq should be widely adaptable to the study of microbial activity in natural environments.
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Affiliation(s)
- Georgia Doing
- The Jackson Laboratory for Genomic Medicine Farmington, Farmington, Connecticut, USA
| | - Priya Shanbhag
- The Jackson Laboratory for Genomic Medicine Farmington, Farmington, Connecticut, USA
| | - Isaac Bell
- The Jackson Laboratory for Genomic Medicine Farmington, Farmington, Connecticut, USA
| | - Sara Cassidy
- The Jackson Laboratory for Genomic Medicine Farmington, Farmington, Connecticut, USA
| | - Efthymios Motakis
- The Jackson Laboratory for Genomic Medicine Farmington, Farmington, Connecticut, USA
| | - Elizabeth Aiken
- The Jackson Laboratory for Genomic Medicine Farmington, Farmington, Connecticut, USA
| | - Julia Oh
- The Jackson Laboratory for Genomic Medicine Farmington, Farmington, Connecticut, USA
| | - Mark D Adams
- The Jackson Laboratory for Genomic Medicine Farmington, Farmington, Connecticut, USA
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25
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Raychaudhuri S, Gem H, Chung K, McLean JS, Kerns KA, Hullar MAJ, Elmorr E, Appelbaum JB, Percival MEM, Walter RB, Halpern AB, Minot SS, Kim K, Zevin AS, Rashidi A. Distal gut colonization by oral bacteria during intensive chemotherapy: direct evidence from strain-level analysis of paired samples. NPJ Biofilms Microbiomes 2025; 11:88. [PMID: 40419513 PMCID: PMC12106833 DOI: 10.1038/s41522-025-00725-7] [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: 01/29/2025] [Accepted: 05/12/2025] [Indexed: 05/28/2025] Open
Abstract
Oral bacteria have been found in the colon in pathologies such as inflammatory bowel disease. To ascertain niche coalescence, 2 elements are essential: (i) paired oral/fecal samples and (ii) strain-level resolution. We profiled the microbiota in 283 samples from 39 patients undergoing intensive chemotherapy at baseline (saliva: 49, plaque: 51, stool: 43), week 2 (saliva: 18, plaque: 17, stool: 17), week 3 (saliva: 18, plaque: 21, stool: 21), and week 4 (saliva: 8, plaque: 10, stool: 10) of chemotherapy. Through strain-level analysis of paired samples, we demonstrate strong evidence for a breakdown of niche separation in most patients. The extent of overlap increased with time, particularly in patients with intestinal mucositis. Our findings provide definitive evidence for ectopic colonization of the distal gut by oral bacteria in a disease state, likely facilitated by intestinal mucositis. Microbiota contribution by the mouth to the colon may have consequences for the host.
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Affiliation(s)
- Suravi Raychaudhuri
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Division of Hematology and Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - Hakan Gem
- Department of Oral Medicine, University of Washington, Seattle, WA, USA
| | - Kevin Chung
- Department of Oral Medicine, University of Washington, Seattle, WA, USA
| | | | - Kristopher A Kerns
- School of Dentistry, University of Washington, Seattle, WA, USA
- Clinical Oral Microbiome Research Center, University of Washington, Seattle, WA, USA
| | - Meredith A J Hullar
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Elissa Elmorr
- School of Dentistry, University of Washington, Seattle, WA, USA
| | - Jacob B Appelbaum
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Division of Hematology and Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - Mary-Elizabeth M Percival
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Division of Hematology and Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - Roland B Walter
- Division of Hematology and Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA
- Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Anna B Halpern
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Division of Hematology and Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - Samuel S Minot
- Data Core, Shared Resources, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Katie Kim
- Genomics and Bioinformatics Shared Resource, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Alexander S Zevin
- Genomics and Bioinformatics Shared Resource, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Armin Rashidi
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
- Division of Hematology and Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
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26
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Yang F, Teng F, Zhang Y, Sun Y, Xu J, Huang S. Single-tooth resolved, whole-mouth prediction of early childhood caries via spatiotemporal variations of plaque microbiota. Cell Host Microbe 2025:S1931-3128(25)00185-4. [PMID: 40449489 DOI: 10.1016/j.chom.2025.05.006] [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: 11/21/2024] [Revised: 03/06/2025] [Accepted: 05/07/2025] [Indexed: 06/03/2025]
Abstract
Early childhood caries (ECC) exhibits tooth specificity, highlighting the need for single-tooth-level prevention. We profiled 2,504 dental plaque microbiota samples from 89 preschoolers across two cohorts, tracking compositional changes with imputed functional trends at a single-tooth resolution over 11 months. In healthy children, dental microbiota exhibited an anterior-to-posterior ecological gradient on maxillary teeth and strong bilateral symmetry. These patterns were disrupted in caries-affected children due to caries-driven microbial reorganization. Leveraging tooth-specific disease-associated taxa and spatially related clinical/microbial features, we developed spatial microbial indicators of caries (spatial-MiC or sMiC) using machine-learning techniques. sMiC achieves 98% accuracy in diagnosing ECC at a single-tooth resolution and 93% accuracy in predicting new caries 2 months in advance in perceived-healthy teeth. This high-resolution spatiotemporal microbial atlas of ECC development disentangles the microbial etiology at the single-tooth level, identifies a characteristic microbial signature for each tooth, and provides a foundation for tooth-specific ECC prevention strategies.
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Affiliation(s)
- Fang Yang
- Department of Stomatology, Qingdao Women and Children's Hospital, Qingdao University, Qingdao 266034, China; Department of Stomatology, Qingdao Municipal Hospital, Qingdao 266001, China
| | - Fei Teng
- Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, Shandong 266001, China; Single-Cell Center, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong 266101, China; Faculty of Dentistry, the University of Hong Kong, Hong Kong SAR, China.
| | - Yufeng Zhang
- Faculty of Dentistry, the University of Hong Kong, Hong Kong SAR, China
| | - Yanfei Sun
- Department of Stomatology, Qingdao Municipal Hospital, Qingdao 266001, China
| | - Jian Xu
- Single-Cell Center, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong 266101, China.
| | - Shi Huang
- Faculty of Dentistry, the University of Hong Kong, Hong Kong SAR, China.
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27
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Jan A, Bayle P, Mohellibi N, Lemoine C, Pepke F, Béguet-Crespel F, Jouanin I, Tremblay-Franco M, Laroche B, Serror P, Rigottier-Gois L. A consortium of seven commensal bacteria promotes gut microbiota recovery and strengthens ecological barrier against vancomycin-resistant enterococci. MICROBIOME 2025; 13:129. [PMID: 40414934 DOI: 10.1186/s40168-025-02127-5] [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: 07/26/2024] [Accepted: 04/29/2025] [Indexed: 05/27/2025]
Abstract
BACKGROUND Vancomycin-resistant enterococci (VRE) often originate from the gastrointestinal tract, where their proliferation precedes dissemination into the bloodstream, and can lead to systemic infection. Uncovering the actors and mechanisms reducing the intestinal colonisation by VRE is essential to control infection. We aimed to identify commensal bacteria that interfere with VRE gut colonisation or act as an ecological barrier. RESULTS We performed a 3-week longitudinal analysis of the gut microbiota composition and VRE carriage levels during microbiota recovery in mice colonised with VRE after antibiotic-induced dysbiosis. By combining biological data and mathematical modelling, we identified 15 molecular species (OTUs) that negatively correlated with VRE overgrowth. Six strains representative of these OTUs were collected, cultivated and used in mixture with a seventh strain (Mix7) in two different mouse lines challenged with VRE. Of the seven strains, three belonged to Lachnospiraceae, one to Muribaculaceae, one to Ruminococcaceae and two to Lactobacillaceae. We found that Mix7 led to a better recovery of the gut microbiota composition and reduced VRE carriage. Differences in the effect of Mix7 were observed between responder and non-responder mice. These differences were associated with variations in the composition of the initial microbiota and during recovery and represent potential biomarkers for predicting response to Mix7. In a mouse model of alternative stable state of dysbiosis, response to Mix7 was associated with higher concentrations of short-chain fatty acids (acetate, propionate, butyrate) and a range of metabolites including bile acids, reflecting the recovery of the microbiota back to initial state. Furthermore, Muribaculum intestinale strain was required to obtain the Mix7 effect on VRE reduction in vivo, but the presence of at least one of the other six strains was needed. None of the supernatant of the seven strains, alone or in combination, inhibited VRE growth in vitro. Interestingly, five strains belong to species shared among humans and mice, and the other two have human functional equivalents. CONCLUSIONS An innovative approach based on mathematical modelling of the microbiota composition permitted to identify a mixture of commensal bacterial strains, which improves the ecological barrier effect against VRE. The mechanisms are dependent on the recovery and initial composition of the microbiota. Ultimately, this work will enable a move towards a personalised medicine by targeting predisposed patients presenting a risk of infection, such as neutropenic or bone-marrow transplant patients, and likely to respond to supplementation with commensal strains, providing new live biotherapeutic products and biomarkers to predict response to supplementation. Video Abstract.
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Affiliation(s)
- Alan Jan
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, F-78350, France
| | - Perrine Bayle
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, F-78350, France
| | - Nacer Mohellibi
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, F-78350, France
| | - Clara Lemoine
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, F-78350, France
| | - Frédéric Pepke
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, F-78350, France
| | - Fabienne Béguet-Crespel
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, F-78350, France
| | - Isabelle Jouanin
- Toxalim - Research Centre in Food Toxicology, INRAE, ENVT, INP-Purpan, Toulouse University, UT3, Toulouse, F-31300, France
- MetaboHUB-MetaToul, National Infrastructure of Metabolomics and Fluxomics, Toulouse, 31077, France
| | - Marie Tremblay-Franco
- Toxalim - Research Centre in Food Toxicology, INRAE, ENVT, INP-Purpan, Toulouse University, UT3, Toulouse, F-31300, France
- MetaboHUB-MetaToul, National Infrastructure of Metabolomics and Fluxomics, Toulouse, 31077, France
| | - Béatrice Laroche
- MaIAGE, INRAE, Université Paris-Saclay, Jouy-en-Josas, 78350, France
- MUSCA, INRIA, Université Paris-Saclay, Palaiseau, 91120, France
| | - Pascale Serror
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, F-78350, France
| | - Lionel Rigottier-Gois
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, F-78350, France.
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28
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Izadifar Z, Stejskalova A, Gulati A, Gutzeit O, Ingber DE. Human Cervix Chip: A Preclinical Model for Studying the Role of the Cervical Mucosa and Microbiome in Female Reproductive Health. Bioessays 2025:e70014. [PMID: 40401380 DOI: 10.1002/bies.70014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 04/04/2025] [Accepted: 04/08/2025] [Indexed: 05/23/2025]
Abstract
Advancements in women's reproductive health have been hindered by insufficient knowledge and the underrepresentation of women in research, leading to symptom-focused care with poor outcomes. Modeling female reproductive biology and disease pathophysiology has been challenging due to the complexity and dynamic nature of the female organs. Here, we briefly review recent advancements made with a new in vitro microfluidic organ-on-a-chip model of the human cervix (Cervix Chip) that faithfully mimics key features of the cervix, including mucus production and physiological responses to hormonal, environmental, and microbial stimuli. We also discuss how this preclinical platform can provide a way to obtain unique insights into the role of mucosal immunity, genetic and risk factors, as well as microbiome and pathogen interactions in human cervix health and disease, while bridging knowledge gaps in fertility and pregnancy-related conditions. By enabling preclinical drug screening and accelerating translational research, the Cervix Chip holds the potential to improve the development of therapeutics, diagnostics, and ultimately, the sexual and reproductive health of millions of women globally.
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Affiliation(s)
- Zohreh Izadifar
- Urology Department, Boston Children's Hospital and Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA
| | - Anna Stejskalova
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA
| | - Aakanksha Gulati
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA
| | - Ola Gutzeit
- IVF Unit, Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, Israel
- Clinical Research Institute at Rambam (CRIR), Rambam Health Care Campus, Haifa, Israel
| | - Donald E Ingber
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA
- Vascular Biology Program, Boston Children's Hospital and Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA
- Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, Massachusetts, USA
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Luo X, Wang K, Jiang C. Gut microbial enzymes and metabolic dysfunction-associated steatohepatitis: Function, mechanism, and therapeutic prospects. Cell Host Microbe 2025:S1931-3128(25)00153-2. [PMID: 40425014 DOI: 10.1016/j.chom.2025.04.020] [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: 02/10/2025] [Revised: 04/28/2025] [Accepted: 04/29/2025] [Indexed: 05/29/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease worldwide. The liver communicates with the intestine, in large part through the gut microbiota. Microbial enzymes are key mediators that affect the progression of MASLD and the more severe metabolic dysfunction-associated steatohepatitis (MASH). These enzymes contribute to the metabolism or biosynthesis of steroids, fatty acids, amino acids, ethanol, choline, and intestinal hormones that contribute to disease progression. Additionally, dysbiosis and functional alterations in the microbiota compromise the intestinal barrier, increasing its permeability to bacterial metabolites and liver exposure to microbial-associated molecular patterns (MAMPs), thereby exacerbating liver inflammation and fibrosis. Furthermore, functional alterations in the gut microbiota can modulate intestinal signaling pathways through metabolites or gut hormones, subsequently affecting hepatic metabolism. A deeper understanding of the roles of the gut microbiota and microbial enzymes in MASH will facilitate the development of personalized treatments targeting specific gut microbes or functional enzymes.
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Affiliation(s)
- Xi Luo
- Department of Physiology and Pathophysiology, Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China
| | - Kai Wang
- Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China.
| | - Changtao Jiang
- Department of Physiology and Pathophysiology, Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.
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30
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Dahal A, Chang WC, Johansson E, Grashel B, Morgan D, Williams L, Hammonds M, Sachdeva S, Spagna D, Satish L, Biagini JM, Martin LJ, Haslam DB, Ollberding NJ, Khurana Hershey GK. Skin Staphylococcus aureus detection and relationship to atopic dermatitis outcomes using culture and metagenomic sequencing. Sci Rep 2025; 15:17606. [PMID: 40399550 PMCID: PMC12095614 DOI: 10.1038/s41598-025-99463-1] [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: 11/12/2024] [Accepted: 04/21/2025] [Indexed: 05/23/2025] Open
Abstract
Staphylococcus aureus (SA) skin colonization in pediatric atopic dermatitis (AD) increases risk for severe AD and development of other allergic diseases. Despite this, there is no consensus regarding the optimal method to detect SA. Studies comparing metagenomic shotgun sequencing (MSS) and culture-based methods in SA detection and relationships to AD outcomes are lacking. In the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort, we defined SA colonization categories by contact agar plate sampling/culture and skin tape sampling/MSS: double negative, sequencing only positive, contact plate only positive, and double positive (n = 759). We assessed AD severity, sensitization, total IgE, and atopic outcomes across categories. Culture missed 69% of samples detected by MSS and MSS missed 54% of samples detected by culture. The double positive group exhibited higher AD severity, sensitization load, and total serum IgE, and was more likely to develop allergic rhinitis (AR) compared to other groups. Detection of SA by MSS or culture missed over half of the SA detected by the other method. Importantly, detection via both methods correlated with increased AD severity, sensitization, total IgE, and AR. Thus, these methods are complementary and both may be necessary for comprehensive evaluation of SA and its clinical and biologic impact.
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Affiliation(s)
- Arya Dahal
- Division of Asthma Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7037, Cincinnati, OH, 45229, USA
- Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA
| | - Wan Chi Chang
- Division of Asthma Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7037, Cincinnati, OH, 45229, USA
| | - Elisabet Johansson
- Division of Asthma Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7037, Cincinnati, OH, 45229, USA
| | - Brittany Grashel
- Division of Asthma Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7037, Cincinnati, OH, 45229, USA
| | - David Morgan
- Division of Asthma Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7037, Cincinnati, OH, 45229, USA
| | - Lindsey Williams
- Division of Asthma Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7037, Cincinnati, OH, 45229, USA
| | - Mindy Hammonds
- Division of Asthma Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7037, Cincinnati, OH, 45229, USA
| | - Seiya Sachdeva
- Division of Asthma Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7037, Cincinnati, OH, 45229, USA
| | - Dan Spagna
- Division of Asthma Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7037, Cincinnati, OH, 45229, USA
| | - Latha Satish
- Division of Asthma Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7037, Cincinnati, OH, 45229, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA
| | - Jocelyn M Biagini
- Division of Asthma Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7037, Cincinnati, OH, 45229, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA
| | - Lisa J Martin
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA
| | - David B Haslam
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA
- Microbial Genomics and Metagenomics Laboratory, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA
| | - Nicholas J Ollberding
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA
| | - Gurjit K Khurana Hershey
- Division of Asthma Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7037, Cincinnati, OH, 45229, USA.
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA.
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31
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Austin GI, Korem T. Compositional transformations can reasonably introduce phenotype-associated values into sparse features. mSystems 2025; 10:e0002125. [PMID: 40314439 PMCID: PMC12090810 DOI: 10.1128/msystems.00021-25] [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: 01/13/2025] [Accepted: 02/13/2025] [Indexed: 05/03/2025] Open
Abstract
Gihawi et al. (mBio 14:e01607-23, 2023, https://doi.org/10.1128/mbio.01607-23) argued that the analysis of tumor-associated microbiome data by Poore et al. (Nature 579:567-574, 2020, https://doi.org/10.1038/s41586-020-2095-1) is invalid because features that were originally very sparse (genera with mostly zero read counts) became associated with the phenotype following batch correction. Here, we examine whether such an observation should necessarily indicate issues with processing or machine learning pipelines. We show counterexamples using the centered log ratio (CLR) transformation, which is often used for analysis of compositional microbiome data. The CLR transformation has similarities to voom-SNM, the batch-correction method brought into question by Gihawi et al., and yet is a sample-wise operation that cannot, in itself, "leak" information or invalidate downstream analyses. We show that because the CLR transformation divides each value by the geometric mean of its sample, common imputation strategies for missing or zero values result in transformed features that are associated with the geometric mean. Through analyses of both synthetic and vaginal microbiome data sets, we demonstrate that when the geometric mean is associated with a phenotype, sparse and CLR-transformed features will also become associated with it. We re-analyze features highlighted by Gihawi et al. and demonstrate that the phenomenon of sparse features becoming phenotype-associated can also be observed after a CLR transformation, which serves as a counterexample to the claim that such an observation necessarily means information leakage. While we do not intend to address other concerns regarding tumor microbiome analyses, validate Poore et al.'s results, or evaluate batch-correction pipelines, we conclude that because phenotype-associated features that were initially sparse can be created by a sample-wise transformation that cannot artifactually inflate machine learning performance, their detection is not independently sufficient to demonstrate information leakage in machine learning pipelines. Microbiome data are multivariate, and as such, a value of 0 carries a different meaning for each sample. Many transformations, including CLR and other batch-correction methods, are likewise multivariate, and, as these issues demonstrate, each individual feature should be interpreted with caution. IMPORTANCE Gihawi et al. claim that finding that a transformation turned highly sparse (mostly zero) features into features that are associated with a phenotype is sufficient to conclude that there is information leakage and to invalidate an analysis. This claim has critical implications for both the debate regarding The Cancer Genome Atlas (TCGA) cancer microbiome analysis and for interpretation and evaluation of analyses in the microbiome field at large. We show by counterexamples and by reanalysis that such transformations can be valid.
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Affiliation(s)
- George I. Austin
- Department of Biomedical Informatics, Columbia University Irving Medical, New York, New York, USA
- Program for Mathematical Genomics, Department of Systems Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - Tal Korem
- Program for Mathematical Genomics, Department of Systems Biology, Columbia University Irving Medical Center, New York, New York, USA
- Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, New York, USA
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Hillman EBM, Baumgartner M, Carson D, Amos GCA, Wazir I, Khan HA, Khan MA, Rijpkema S, Walters JRF, Wellington EMH, Arasaradnam R, Lewis SJ. Changing Gastrointestinal Transit Time Alters Microbiome Composition and Bile Acid Metabolism: A Cross-Over Study in Healthy Volunteers. Neurogastroenterol Motil 2025:e70075. [PMID: 40394972 DOI: 10.1111/nmo.70075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 03/21/2025] [Accepted: 04/30/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND The specific influence of whole gut transit time (WGTT) on microbiome dynamics and bile acid metabolism remains unclear, despite links between changes in WGTT and certain gastrointestinal disorders. Our investigation aimed to determine the impact of WGTT changes on the composition of the fecal microbiome and bile acid profile. METHODS Healthy volunteers (n = 18) received loperamide, to decrease bowel movement frequency, and senna, a laxative, each over a 6-day period, in a randomized sequence, with a minimum 16-day interval between each treatment. Stool samples were analyzed for microbiome by shotgun sequencing and bile acid composition determined with high-performance liquid chromatography coupled to tandem mass spectrometry. Sera were examined for markers of bile acid synthesis. KEY RESULTS Senna or loperamide decreased or increased WGTT, respectively. Treatment altered stool characteristics, bowel movement frequency, and stool weight. The senna-treated group had increased primary and secondary fecal bile acids; serum levels of fibroblast growth factor 19 were significantly reduced. Increasing WGTT with loperamide led to an increase in bile salt hydrolase genes, along with elevated bacterial species richness (p = 0.04). Thirty-six species exhibiting significant differences were identified, several of which have notable implications for gut health. WGTT displayed negative correlations with total primary (particularly chenodeoxycholic acid) and secondary bile acids (ursodeoxycholic acid and glycochenodeoxycholic acid). Treatment-induced changes in microbiome composition and bile acid metabolism reverted back to baseline within 16 days. CONCLUSION Whole gut transit time changes significantly affect fecal microbiome composition and function, as well as bile acid composition and synthesis in healthy subjects. This consideration is likely to have long-term implications.
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Affiliation(s)
- Evette B M Hillman
- Diagnostics, Medicines and Healthcare Products Regulatory Agency, London, UK
- School of Life Sciences, The University of Warwick, Coventry, UK
| | - Maximilian Baumgartner
- Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Danielle Carson
- Diagnostics, Medicines and Healthcare Products Regulatory Agency, London, UK
| | - Gregory C A Amos
- Diagnostics, Medicines and Healthcare Products Regulatory Agency, London, UK
| | - Imad Wazir
- Department of Gastroenterology, University Hospital Plymouth, Plymouth, UK
| | - Haider A Khan
- Department of Gastroenterology, University Hospital Plymouth, Plymouth, UK
| | - Malik A Khan
- Department of Gastroenterology, University Hospital Plymouth, Plymouth, UK
| | - Sjoerd Rijpkema
- Diagnostics, Medicines and Healthcare Products Regulatory Agency, London, UK
| | - Julian R F Walters
- Division of Digestive Diseases, Imperial College London, London, UK
- Imperial College Healthcare Trust, London, UK
| | | | - Ramesh Arasaradnam
- Department of Gastroenterology, University Hospitals Coventry & Warwickshire, Coventry, UK
- Warwick Medical School, The University of Warwick, Coventry, UK
| | - Stephen J Lewis
- Department of Gastroenterology, University Hospital Plymouth, Plymouth, UK
- Peninsula Medical School, University of Plymouth, Plymouth, UK
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Deng L, Guan G, Cannon RD, Mei L. Age-related oral microbiota dysbiosis and systemic diseases. Microb Pathog 2025; 205:107717. [PMID: 40403989 DOI: 10.1016/j.micpath.2025.107717] [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: 01/15/2025] [Revised: 05/08/2025] [Accepted: 05/17/2025] [Indexed: 05/24/2025]
Abstract
The oral microbiota is an essential microbial community within the human body, playing a vital role in maintaining health. In older adults, age-related changes in the oral microbiota are linked to both systemic and oral health impairments. The use of various medications for systemic diseases in the elderly can also contribute to the development of oral diseases. Oral microbiota dysbiosis refers to an imbalance in the composition of oral microbial communities. This imbalance, along with disruptions in the host immune response and prolonged inflammation, is closely associated with the onset and progression of several diseases. It contributes to oral conditions such as dental caries, periodontal disease, and halitosis. It is also linked to systemic diseases, including Alzheimer's disease, type 2 diabetes mellitus, rheumatoid arthritis, atherosclerotic cardiovascular disease, and aspiration pneumonia. This review aims to explore how oral microbiota influences specific health outcomes in older individuals, focusing on Alzheimer's disease, type 2 diabetes mellitus, rheumatoid arthritis, atherosclerotic cardiovascular disease, and aspiration pneumonia. The oral microbiota holds promise as a diagnostic tool, therapeutic target, and prognostic biomarker for managing cardiovascular disease, metabolic diseases, infectious diseases and autoimmune diseases. Emphasizing proper oral health care and instilling an understanding of how drugs prescribed for systemic disease impact the oral microbiome, is anticipated to emerge as a key strategy for promoting the general health of older adults.
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Affiliation(s)
- Ling Deng
- Department of Oral Pathology, The Affiliated Stomatological Hospital of Guizhou Medical University, Guiyang, PR China
| | - Guangzhao Guan
- Department of Oral Diagnostic and Surgical Sciences, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.
| | - Richard D Cannon
- Department of Oral Sciences, Faculty of Dentistry, University of Otago, Dunedin, New Zealand
| | - Li Mei
- Department of Oral Sciences, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.
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Wang J, Gao S, Xu Z, Yang Z, Mu Q, Li Z, Liu P, Hu J, Bao Z. Unveiling the Characteristics of Microbiota in Different Mucosal Layers of Leopard Coral Grouper (Plectropomus leopardus). MARINE BIOTECHNOLOGY (NEW YORK, N.Y.) 2025; 27:86. [PMID: 40392419 DOI: 10.1007/s10126-025-10458-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Accepted: 04/14/2025] [Indexed: 05/22/2025]
Abstract
Mucosal microbiomes play an important role in digestion, nutrition, and resistance to pathogens and toxins in fish; thus, characterizing the mucosal microbiomes of economically important fish species is paramount. In this study, mucosal microbiomes of healthy leopard coral grouper (Plectropomus leopardus), which is of economic importance worldwide, were systematically analyzed and compared by using 16S rRNA amplicon sequencing. The analysis of alpha-diversity and beta-diversity revealed significant differences in the structure and composition of the microbial community between different mucosal layers of P. leopardus. The skin microbiota showed the lowest microbial diversity among the three tissues, and the highest interindividual variability within gill groups was observed. Proteobacteria is the dominant phylum of the gut, skin, and gill microbiomes. Microbial biomarkers of the three mucosal tissues were identified, with the genera Parvibaculum, Aminobacter, Sphingobium, and Ralstonia for skin; Mesoflavibacter, Winogradskyella, Malaciobacter, Nautella, and Marinobacterium for gills; and Cetobacterium, Photobacterium, and Vibrio for gut. These genera were also the core microorganisms in each tissue. A large number of identical pathways of the three mucosal surfaces microbiome (e.g., pathways related to metabolism, human diseases, genetic/environmental information processing) and some specifically enriched pathways in each tissue were identified. Co-occurrence network analysis revealed that there were more ecological communities and higher functional diversity in the gill microbiota, and the interactions between gut microbiota are closer and more stable. Our study provides a new perspective for a comprehensive understanding of the mucosal microbiota of P. leopardus, contributing to an in-depth exploration of the interaction between fish and microorganisms, and may help to predict potential disease outbreaks, thus promoting the development of the fish farming industry.
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Affiliation(s)
- Jiahui Wang
- Key Laboratory of Tropical Aquatic Germplasm of Hainan Province, Sanya Oceanographic Institution, Ocean University of China, Sanya, 572025572000, China
| | - Shengtao Gao
- Key Laboratory of Tropical Aquatic Germplasm of Hainan Province, Sanya Oceanographic Institution, Ocean University of China, Sanya, 572025572000, China
| | - Zhenyuan Xu
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China
| | - Zhihui Yang
- Key Laboratory of Tropical Aquatic Germplasm of Hainan Province, Sanya Oceanographic Institution, Ocean University of China, Sanya, 572025572000, China
| | - Qianqian Mu
- Key Laboratory of Tropical Aquatic Germplasm of Hainan Province, Sanya Oceanographic Institution, Ocean University of China, Sanya, 572025572000, China
| | - Zijian Li
- Key Laboratory of Tropical Aquatic Germplasm of Hainan Province, Sanya Oceanographic Institution, Ocean University of China, Sanya, 572025572000, China
| | - Pingping Liu
- Key Laboratory of Tropical Aquatic Germplasm of Hainan Province, Sanya Oceanographic Institution, Ocean University of China, Sanya, 572025572000, China.
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China.
| | - Jingjie Hu
- Key Laboratory of Tropical Aquatic Germplasm of Hainan Province, Sanya Oceanographic Institution, Ocean University of China, Sanya, 572025572000, China.
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China.
| | - Zhenmin Bao
- Key Laboratory of Tropical Aquatic Germplasm of Hainan Province, Sanya Oceanographic Institution, Ocean University of China, Sanya, 572025572000, China
- MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China
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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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Di Pierro F, Ficuccilli F, Tessieri L, Menasci F, Pasquale C, Khan A, Rabbani F, Memon NM, Cazzaniga M, Bertuccioli A, Matera M, Cavecchia I, Recchia M, Palazzi CM, Tanda ML, Zerbinati N. Irritable Bowel Syndrome with Diarrhea (IBS-D): Effects of Clostridium butyricum CBM588 Probiotic on Gastrointestinal Symptoms, Quality of Life, and Gut Microbiota in a Prospective Real-Life Interventional Study. Microorganisms 2025; 13:1139. [PMID: 40431311 PMCID: PMC12113862 DOI: 10.3390/microorganisms13051139] [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: 04/08/2025] [Revised: 05/04/2025] [Accepted: 05/11/2025] [Indexed: 05/29/2025] Open
Abstract
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional gastrointestinal disorder characterized by altered motility, abdominal pain, and dysbiosis-particularly reduced biodiversity and a lower abundance of butyrate-producing bacteria. Strategies that modulate the gut microbiota may offer therapeutic benefit. Clostridium butyricum (C. butyricum) CBM588 is a butyrate-producing probiotic with immunomodulatory properties and potential efficacy in treating gastrointestinal disorders. This pragmatic, prospective, open-label, single-arm interventional study assessed the clinical, microbial, and safety-related effects of an 8-week CBM588 supplementation, along with a low-fiber and low-residue diet, in 205 patients with IBS-D who attended Quisisana Nursing Home Hospital, Rome, Italy, between November 2024 and February 2025. The primary outcomes included the global symptom response, the Bristol Stool Scale (BSS), stool frequency, diarrhea episodes, abdominal pain (severity and frequency), bloating, bowel dissatisfaction, quality of life (QoL), safety, and treatment tolerability-measured using the IBS Symptom Severity Scale (IBS-SSS) and a standardized tolerability scale. CBM588, in patients treated with a low-fiber and low-residue diet, significantly improved all clinical endpoints, with a >80% reduction in diarrhea episodes; ~60% reductions in stool frequency and abdominal pain; and >50% improvements in bloating, bowel dissatisfaction, and QoL. Treatment was well tolerated (mean tolerability score 8.95 ± 0.88), with >95% adherence, and no serious adverse events were reported. The secondary outcomes included changes in gut microbiota. In a subset of patients, 16S rRNA gene sequencing showed increased α-diversity and enrichment of butyrate-producing genera (Agathobacter, Butyricicoccus, Coprococcus), which correlated with symptom improvement. Bloating increased in some patients, possibly related to fermentation activity. These findings support the C. butyricum CBM588 probiotic strain as a safe, well-tolerated, and microbiota-targeted intervention for IBS-D. Randomized controlled trials are warranted to confirm efficacy.
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Affiliation(s)
- Francesco Di Pierro
- Microbiota International Clinical Society, 10123 Turin, Italy; (F.D.P.); (C.M.P.)
- Scientific & Research Department, Velleja Research, 20125 Milan, Italy;
- Department of Medicine and Technological Innovation, University of Insubria, 21100 Varese, Italy;
| | | | - Laura Tessieri
- Nursing Home Quisisana, 00197 Rome, Italy; (F.F.); (L.T.); (F.M.); (C.P.)
| | - Francesca Menasci
- Nursing Home Quisisana, 00197 Rome, Italy; (F.F.); (L.T.); (F.M.); (C.P.)
| | - Chiara Pasquale
- Nursing Home Quisisana, 00197 Rome, Italy; (F.F.); (L.T.); (F.M.); (C.P.)
| | - Amjad Khan
- Department of Biochemistry, Liaquat University of Medical & Health Sciences (LUMHS), Jamshoro 76090, Pakistan
| | - Fazle Rabbani
- Department of Psychiatry, Lady Reading Hospital (LRH), Peshawar 25000, Pakistan
| | - Nazia Mumtaz Memon
- Department of Pathology, Liaquat University of Medical and Health Sciences (LUMHS), Jamshoro 76090, Pakistan;
| | | | - Alexander Bertuccioli
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy;
| | - Mariarosaria Matera
- Department of Pediatric Emergencies, Misericordia Hospital, 58100 Grosseto, Italy;
| | - Ilaria Cavecchia
- Microbiota International Clinical Society, 10123 Turin, Italy; (F.D.P.); (C.M.P.)
- Microbiomic Department, Koelliker Hospital, 10134 Turin, Italy
| | - Martino Recchia
- Unit of Clinical Epidemiology and Biostatistics, Mario Negri Institute Alumni Association (MNIAA), 20156 Milan, Italy;
| | - Chiara Maria Palazzi
- Microbiota International Clinical Society, 10123 Turin, Italy; (F.D.P.); (C.M.P.)
| | - Maria Laura Tanda
- Endocrine Unit, Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy;
| | - Nicola Zerbinati
- Department of Medicine and Technological Innovation, University of Insubria, 21100 Varese, Italy;
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Guo Y, Sun S, Wang Y, Chen S, Kou Z, Yuan P, Han W, Yu X. Microbial dysbiosis in obstructive sleep apnea: a systematic review and meta-analysis. Front Microbiol 2025; 16:1572637. [PMID: 40444003 PMCID: PMC12119640 DOI: 10.3389/fmicb.2025.1572637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Accepted: 05/01/2025] [Indexed: 06/02/2025] Open
Abstract
Background The association between the microbiota and obstructive sleep apnea (OSA) remains understudied. In this study, we conducted a comprehensive systematic review and meta-analysis of studies investigating the diversity and relative abundance of microbiota in the gut, respiratory tracts and oral cavity of patients with OSA, aiming to provide an in-depth characterization of the microbial communities associated with OSA. Methods A comprehensive literature search across PubMed, the Cochrane Library, Web of Science, and Embase databases were conducted to include studies published prior to Dec 2024 that compared the gut, respiratory and oral microbiota between individuals with and without OSA. The findings regarding alpha-diversity, beta-diversity, and relative abundance of microbiota extracted from the included studies were summarized. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the study protocol was registered with PROSPERO (CRD42024525114). Results We identified a total of 753 articles, out of which 27 studies were ultimately included in the systematic review, involving 1,381 patients with OSA and 692 non-OSA populations, including 1,215 OSA patients and 537 non-OSA populations in adults and 166 OSA patients and 155 non-OSA populations in children. The results of alpha diversity revealed a reduction in the Chao1 index (SMD = -0.40, 95% CI = -0.76 to -0.05), Observed species (SMD = -0.50, 95% CI = -0.89 to -0.12) and Shannon index (SMD = -0.27, 95% CI = -0.47 to -0.08) of the gut microbiota in patients with OSA. Beta diversity analysis indicated significant differences in the gut, respiratory and oral microbial community structure between individuals with OSA and those without in more than half of the included studies. Furthermore, in comparison to the non-OSA individuals, the gut environment of patients with OSA exhibited an increased relative abundance of phylum Firmicutes, along with elevated levels of genera Lachnospira; conversely, there was a decreased relative abundance of phylum Bacteroidetes and genus Ruminococcus and Faecalibacterium. Similarly, within the oral environment of OSA patients, there was an elevated relative abundance of phylum Actinobacteria and genera Neisseria, Rothia, and Actinomyces. Conclusion Patients with OSA exhibit reduced diversity, changes in bacterial abundance, and altered structure in the microbiota, especially in the gut microbiota. The results of this study provide basic evidence for further exploration of microbiome diagnostic markers and potential intervention strategies for OSA.
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Affiliation(s)
- Yang Guo
- School of Medical Laboratory, Shandong Second Medical University, Weifang, China
| | - Shuqi Sun
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China
| | - Yaoyao Wang
- Department of Medicine, Qingdao University, Qingdao, China
| | - Shiyang Chen
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China
| | - Ziwei Kou
- Department of Medicine, Qingdao University, Qingdao, China
| | - Peng Yuan
- Qingdao Key Laboratory of Common Diseases, Department of Respiratory and Critical Medicine, Department of Emergency, Department of General Practice, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, China
| | - Wei Han
- Qingdao Key Laboratory of Common Diseases, Department of Respiratory and Critical Medicine, Department of Emergency, Department of General Practice, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, China
| | - Xinjuan Yu
- Clinical Research Center, Qingdao Key Laboratory of Common Diseases, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, China
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Abiru S, Kugiyama Y, Suehiro T, Motoyoshi Y, Saeki A, Nagaoka S, Yamasaki K, Komori A, Yatsuhashi H. Lactitol may improve the prognosis of hepatocellular carcinoma through the proliferation of Megasphaera as well as Bifidobacterium. Front Med (Lausanne) 2025; 12:1567849. [PMID: 40438352 PMCID: PMC12116508 DOI: 10.3389/fmed.2025.1567849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 04/28/2025] [Indexed: 06/01/2025] Open
Abstract
Background Increasing evidence suggests that gut microbiota and their metabolites can modulate antitumor immunity. However, sufficient evidence from human studies is lacking. We evaluated the association of lactitol and lactulose as prebiotics with the progression of hepatocellular carcinoma (HCC). Methods In Study 1, the effects of lactitol and lactulose on overall survival (OS) of patients with HCC with Child-Pugh scores of B or C were investigated in patients diagnosed at the Nagasaki Medical Center between 2003 and 2020. In Study 2, the effects of these substances on the gut microbiota of patients with cirrhosis were analyzed. Study 3 examined the effect of these substances on serum albumin levels in patients with cirrhosis. Results In Study 1, a total of 321 patients were evaluated, and 55 pairs of Lactitol and Non-Lactitol groups and 80 pairs of Lactulose and Non-Lactulose groups were created using one to one propensity score matching. The Lactitol group showed a significant improvement (p < 0.05) in OS compared to the Non-Lactitol group, but the Lactulose group did not show any significance compared to the Non-Lactulose group. In Study 2, the number of Bifidobacterium was higher in the Lactitol group and the Lactulose group than in the Control group, but the number of Megasphaera was significantly higher only in the Lactitol group. In addition, in a study of 10 cases in which the gut microbiota was examined before and after lactitol use, an increase in Bifidobacterium and Megasphaera was observed after lactitol use. Study 3 found that lactitol had no beneficial effect on serum albumin levels. Conclusion Lactitol may improve the prognosis of HCC through the proliferation of Megasphaera as well as Bifidobacterium.
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Affiliation(s)
- Seigo Abiru
- Department of Internal Medicine, NHO Saga Hospital, Saga, Japan
- Clinical Research Center, NHO Nagasaki Medical Center, Nagasaki, Japan
| | - Yuki Kugiyama
- Clinical Research Center, NHO Nagasaki Medical Center, Nagasaki, Japan
| | - Tomoyuki Suehiro
- Clinical Research Center, NHO Nagasaki Medical Center, Nagasaki, Japan
| | | | - Akira Saeki
- Clinical Research Center, NHO Nagasaki Medical Center, Nagasaki, Japan
| | - Shinya Nagaoka
- Clinical Research Center, NHO Nagasaki Medical Center, Nagasaki, Japan
| | - Kazumi Yamasaki
- Clinical Research Center, NHO Nagasaki Medical Center, Nagasaki, Japan
| | - Atsumasa Komori
- Clinical Research Center, NHO Nagasaki Medical Center, Nagasaki, Japan
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Baker JS, Qu E, Mancuso CP, Tripp AD, Conwill A, Lieberman TD. Intraspecies dynamics underlie the apparent stability of two important skin microbiome species. Cell Host Microbe 2025; 33:643-656.e7. [PMID: 40315837 DOI: 10.1016/j.chom.2025.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 03/29/2025] [Accepted: 04/11/2025] [Indexed: 05/04/2025]
Abstract
Adult human facial skin microbiomes are remarkably similar at the species level, dominated by Cutibacterium acnes and Staphylococcus epidermidis, yet each person harbors a unique community of strains. Understanding how person-specific communities assemble is critical for designing microbiome-based therapies. Here, using 4,055 isolate genomes and 356 metagenomes, we reconstruct on-person evolutionary history to reveal on- and between-person strain dynamics. We find that multiple cells are typically involved in transmission, indicating ample opportunity for migration. Despite this accessibility, family members share only some of their strains. S. epidermidis communities are dynamic, with each strain persisting for an average of only 2 years. C. acnes strains are more stable and have a higher colonization rate during the transition to an adult facial skin microbiome, suggesting this window could facilitate engraftment of therapeutic strains. These previously undetectable dynamics may influence the design of microbiome therapeutics and motivate the study of their effects on hosts.
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Affiliation(s)
- Jacob S Baker
- Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Evan Qu
- Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Christopher P Mancuso
- Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - A Delphine Tripp
- Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Systems Biology, Harvard University, Cambridge, MA 02138, USA
| | - Arolyn Conwill
- Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Tami D Lieberman
- Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
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Crouch AL, Severance BM, Creary S, Hood D, Bailey M, Mejias A, Ramilo O, Gillespie M, Ebelt S, Sheehan V, Kopp BT, Anderson MZ. Altered nasal and oral microbiomes define pediatric sickle cell disease. mSphere 2025:e0013725. [PMID: 40366139 DOI: 10.1128/msphere.00137-25] [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: 02/28/2025] [Accepted: 04/09/2025] [Indexed: 05/15/2025] Open
Abstract
Sickle cell disease (SCD) is a chronic blood disorder that disrupts multiple organ systems and can lead to severe morbidity. Persistent and acute symptoms caused by immune system dysregulation in individuals with SCD could contribute to disease either directly or indirectly via dysbiosis of commensal microbes and increased susceptibility to infection. Here, we explored the nasal and oral microbiomes of children with SCD (cwSCD) to uncover potential dysbiotic associations with the blood disorder. Microbiota collected from nasal and oral swabs of 40 cwSCD were compared to eight healthy siblings using shotgun metagenomic sequencing. Commensal taxa were present at similar levels in the nasal and oral microbiome of both groups. However, the nasal microbiomes of cwSCD contained a higher prevalence of Pseudomonadota species, including pathobionts such as Yersinia enterocolitica and Klebsiella pneumoniae. Furthermore, the oral microbiome of cwSCD displayed lower α-diversity and fewer commensal and pathobiont species compared to the healthy siblings. Thus, subtle but notable shifts seem to exist in the nasal and oral microbiomes of cwSCD, suggesting an interaction between SCD and the microbiome that may influence health outcomes. IMPORTANCE The oral and nasal cavities are susceptible to environmental exposures including pathogenic microbes. In individuals with systemic disorders, antibiotic exposure, changes to the immune system, or changes to organ function could influence the composition of the microbes at these sites and the overall health of individuals. Children with sickle cell disease (SCD) commonly experience respiratory infections, such as pneumonia or sinusitis, and may have increased susceptibility to infection because of disrupted microbiota at these body sites. We found that children with SCD (cwSCD) had more pathobiont bacteria in the nasal cavity and reduced bacterial diversity in the oral cavity compared to their healthy siblings. Defining when, why, and how these changes occur in cwSCD could help identify specific microbial signatures associated with susceptibility to infection or adverse outcomes, providing insights into personalized treatment strategies and preventive measures.
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Affiliation(s)
- Audra L Crouch
- Department of Microbiology, The Ohio State University, Columbus, Ohio, USA
| | - Beatrice M Severance
- Laboratory of Genetics, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Susan Creary
- Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Darryl Hood
- College of Public Health, The Ohio State University, Columbus, Ohio, USA
| | - Michael Bailey
- Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Asuncion Mejias
- Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Octavio Ramilo
- Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Michelle Gillespie
- Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Stefanie Ebelt
- Environmental Health and Epidemiology, Rollins School of Public Health at Emory University, Atlanta, Georgia, USA
| | | | - Benjamin T Kopp
- Children's Healthcare of Atlanta, Atlanta, Georgia, USA
- Division of Pulmonology, Asthma, Cystic Fibrosis, and Sleep, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Matthew Z Anderson
- Department of Microbiology, The Ohio State University, Columbus, Ohio, USA
- Laboratory of Genetics, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, USA
- Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, Wisconsin, USA
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Yu J, Liang Y, Zhang Q, Ding H, Xie M, Zhang J, Hu W, Xu S, Xiao Y, Xu S, Na R, Wu B, Zhou J, Chen H. An interplay between human genetics and intratumoral microbiota in the progression of colorectal cancer. Cell Host Microbe 2025; 33:657-670.e6. [PMID: 40306270 DOI: 10.1016/j.chom.2025.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 01/10/2025] [Accepted: 04/04/2025] [Indexed: 05/02/2025]
Abstract
Intratumoral microbiota plays a crucial role in cancer progression. However, the relationship between host genetics and intratumoral microbiota, as well as their interaction in colorectal cancer (CRC) progression, remains unclear. With 748 Chinese CRC patients enrolled from three cohorts, we find that the single nucleotide polymorphism (SNP) rs2355016, located in the intron of ATP-sensitive inward rectifier potassium channel 11 (KCNJ11), is significantly associated with the abundance of Fusobacterium. Compared with the rs2355016 GG genotype, patients carrying the A allele exhibit downregulation of KCNJ11 and enrichment of Fusobacterium, which corresponds to accelerated proliferation and progression. Low expression of KCNJ11 can increase the level of galactose-N-acetyl-d-galactosamine (Gal-GalNAc) on the surface of CRC cells, thereby facilitating the binding of the Fap2 protein from F. nucleatum to Gal-GalNAc. This further enhances the adhesion and invasion of F. nucleatum and promotes CRC growth. Our study explores the interaction between intratumoral microbiota and SNPs in CRC patients, which will enhance our understanding of CRC proliferation.
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Affiliation(s)
- Jing Yu
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China
| | - Yuxuan Liang
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Qingrong Zhang
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Hui Ding
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510655, China
| | - Minghao Xie
- Department of General Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330038, China
| | - Jingjing Zhang
- Cancer Hospital Chinese Academy of Medical Sciences Shenzhen Center, Shenzhen, Guangdong 518116, China
| | - Wenyan Hu
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Sihua Xu
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Yiyuan Xiao
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Sha Xu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, China
| | - Rong Na
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China.
| | - Baixing Wu
- Institute of Drug Discovery, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
| | - Jiaming Zhou
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China.
| | - Haitao Chen
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong 510275, China; Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety, School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
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Harrington K, Shah K. Harmonizing the Gut Microbiome and Cellular Immunotherapies: The Next Leap in Cancer Treatment. Cells 2025; 14:708. [PMID: 40422211 DOI: 10.3390/cells14100708] [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: 03/10/2025] [Revised: 05/06/2025] [Accepted: 05/06/2025] [Indexed: 05/28/2025] Open
Abstract
The gut microbiome, a diverse community of microorganisms, plays a key role in shaping the host's immune system and modulating cancer therapies. Emerging evidence highlights its critical influence on the efficacy and toxicity of cell-based immunotherapies, including chimeric antigen receptor T cell, natural killer cell, and stem cell therapies. This review explores the interplay between gut microbiota and cellular immunotherapies, focusing on mechanisms by which microbial metabolites and microbial composition impact treatment outcomes. Furthermore, we discuss strategies to leverage the gut microbiome to optimize therapeutic efficacy and minimize adverse effects. A deeper understanding of the relationship between the gut microbiome and cellular immunotherapies can pave the way for more effective cell-based therapies for cancer.
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Affiliation(s)
- Kendall Harrington
- Center for Stem Cell and Translational Immunotherapy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
- Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Khalid Shah
- Center for Stem Cell and Translational Immunotherapy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
- Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
- Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA
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McDonald TK, Aqeel A, Neubert B, Bauer A, Jiang S, Osborne O, Ives N, Jiang D, Bucardo F, Gutiérrez L, Zambrana L, Jenkins K, Gilner J, Rodriguez J, Lai A, Smith JP, Song R, Ahsan K, Ahmed S, Soomro SI, Umrani F, Barratt M, Gordon JI, Ali A, Iqbal N, Hurst JH, Martin V, Shreffler W, Yuan Q, Brown JM, Surana NK, Vilchez S, Becker-Dreps S, David LA. Dietary plant diversity predicts early life microbiome maturation. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2025.02.28.25323117. [PMID: 40093214 PMCID: PMC11908320 DOI: 10.1101/2025.02.28.25323117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Abstract
Despite established links between the infant gut microbiome and health, how complementary feeding shapes colonization remains unclear. Using FoodSeq, a DNA-based dietary assessment technique, we surveyed food intake across 729 children (0-3 y) from North and Central America, Africa, and Asia. We detected 199 unique plant food sequences, with only eight staples shared across all countries. Despite this global variation, early-life diets followed a common trajectory: weaning stage emerged as the dominant dietary signature across populations. Crucially, dietary diversity did not correlate with gut microbial diversity. Instead, dietary diversity and weaning stage specifically predicted the abundance of adult-associated bacteria. Our findings support a two-stage maturation model: an initial milk-dominated phase, followed by a diet-responsive phase that yields adult-like communities. Monitoring and promoting plant dietary diversity may thus support timely microbiome maturation worldwide.
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Ellis E, Fulte S, Boylan S, Flory A, Paine K, Lopez S, Allen G, Warya K, Ortiz-Merino J, Blacketer S, Thompson S, Sanchez S, Burdette K, Duchscherer A, Pinkham N, Shih JD, Rahn-Lee L. Community living causes changes in metabolic behavior and is permitted by specific growth conditions in two bacterial co-culture systems. J Bacteriol 2025:e0007525. [PMID: 40366143 DOI: 10.1128/jb.00075-25] [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: 04/16/2025] [Indexed: 05/15/2025] Open
Abstract
Although bacteria exist in complex microbial communities in the environment, their features and behavior are most often studied in monoculture. While environmental enrichments or complex co-cultures with tens or hundreds of members might more accurately represent the natural communities of bacteria, we sought to create simple pairs of organisms to learn what conditions create successful co-culture and how bacteria change transcriptionally when a partner species is present. We grew two pairs of organisms in co-culture, Pseudomonas aeruginosa and Escherichia coli and Lacticaseibacillus rhamnosus and Bacteroides thetaiotaomicron. At first, both co-cultures failed, with one organism outcompeting the other. However, through manipulating media and environmental conditions, we created co-cultures with stable member ratios over many generations for each community. We then show that changes in the expression of metabolic genes are present in all studied species, with key catabolic and anabolic pathways often upregulated in the presence of another organism. These changes in gene expression fail to occur in conditions that will not lead to successful co-culture, suggesting they are essential for adapting to and surviving in the presence of others. IMPORTANCE In 1882, Robert Koch and Fanny Hesse developed the agar plate, which enabled microbiologists to separate individual microbial cells from each other and create monocultures of a single strain of bacteria. This powerful tool has been used in the almost 150 years since to develop a robust understanding of how bacterial cells are structured, how they manage and process their information, and how they respond to the environment to produce behaviors that match their circumstances. We were curious about how the behavior of bacteria, as measured by their gene expression, changes between well-studied monoculture conditions and co-culture. We found that only specific growth conditions permit co-culture and that bacteria change their metabolic strategies in the presence of a partner.
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Affiliation(s)
- Elizabeth Ellis
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | - Sam Fulte
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | - Skyler Boylan
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | - Alaina Flory
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | - Katherine Paine
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | - Sophia Lopez
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | - Grace Allen
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | - Kanwar Warya
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | | | - Sadie Blacketer
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | - Samantha Thompson
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | - Sierra Sanchez
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | - Kayla Burdette
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | | | - Nick Pinkham
- Department of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USA
| | - Joseph D Shih
- Department of Biology, William Jewell College, Liberty, Missouri, USA
| | - Lilah Rahn-Lee
- Department of Biology, William Jewell College, Liberty, Missouri, USA
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Netter U, Bisht V, Gaurav A, Sharma R, Ghosh A, Bisht VS, Ambatipudi K, Sharma HP, Mohanty S, Loat S, Sarkar M, Tahlan K, Navani NK. Discovery and mechanistic characterization of a probiotic-origin 3β-OH-Δ 5-6-cholesterol-5β-reductase directly converting cholesterol to coprostanol. FEBS J 2025. [PMID: 40364602 DOI: 10.1111/febs.70131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 03/21/2025] [Accepted: 04/25/2025] [Indexed: 05/15/2025]
Abstract
Cholesterol serves as a fundamental molecule in various structural and biochemical pathways; however, high cholesterol levels are linked to cardiovascular diseases. Some selected strains of Lactobacilli are known for modulating cholesterol levels. However, the molecular mechanism underlying cholesterol transformation by lactobacilli has remained elusive. This study describes the discovery and function of a microbial 3β-OH-Δ5-6-cholesterol-5β-reductase (5βChR) from Limosilactobacillus fermentum NKN51, which directly converts cholesterol to coprostanol, thereby unraveling this longstanding mystery. Protein engineering of the reductase enzyme identified the cholesterol and NADPH interacting amino acid residues, detailing the catalytic mechanism of 5βChR. Phylogenetic analyses highlight the prevalence of 5βChRs in gut commensal lactobacilli, which share a common evolutionary origin with plant 5β reductases. Meta-analysis of microbiomes from healthy individuals underscores the importance of 5βChR homologs, while a cohort study demonstrates an inverse association between 5βChR abundance and diabetes. The discovery of the 5βChR enzyme and its molecular mechanism in cholesterol metabolism paves the way for a better understanding of the gut-associated microbiome and the design of practical applications to ameliorate dyslipidemia.
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Affiliation(s)
- Urmila Netter
- Chemical Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, India
| | - Vishakha Bisht
- Chemical Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, India
| | - Amit Gaurav
- Chemical Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, India
| | - Rekha Sharma
- Chemical Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, India
| | - Avik Ghosh
- Chemical Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, India
| | - Vinod Singh Bisht
- Proteomics and Lipidomics Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, India
| | - Kiran Ambatipudi
- Proteomics and Lipidomics Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, India
| | - Hanuman Prasad Sharma
- Centralized Core Research Facility, All India Institute of Medical Sciences, New Delhi, India
| | - Sujata Mohanty
- Stem Cell Facility (DBT-Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi, India
| | - Shubham Loat
- ICAR-National Research Centre on Yak, Dirang, India
| | - Mihir Sarkar
- ICAR-National Research Centre on Yak, Dirang, India
| | - Kapil Tahlan
- Department of Biology, Memorial University of Newfoundland and Labrador, St. John's, Canada
| | - Naveen K Navani
- Chemical Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, India
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Fernandez E, Wargo JA, Helmink BA. The Microbiome and Cancer: A Translational Science Review. JAMA 2025:2833859. [PMID: 40354071 DOI: 10.1001/jama.2025.2191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Importance Growing evidence suggests that microbes located within the gastrointestinal tract and other anatomical locations influence the development and progression of diseases such as cancer. Observations Clinical and preclinical evidence suggests that microbes in the gastrointestinal tract and other anatomical locations, such as the respiratory tract, may affect carcinogenesis, development of metastases, cancer treatment response, and cancer treatment-related adverse effects. Within tumors of patients with cancer, microbes may affect response to treatment, and therapies that reduce or eliminate these microbes may improve outcomes in patients with cancer. Modulating gastrointestinal tract (gut) microbes through fecal microbiota transplant and other strategies such as dietary intervention (eg, high-fiber diet intervention) has improved outcomes in small studies of patients treated with cancer immunotherapy. In contrast, disruption of the gut microbiota by receipt of broad-spectrum antibiotics prior to treatment with cancer immunotherapy has been associated with poorer overall survival and higher rates of adverse effects in patients treated with immune checkpoint blockade for solid tumors and also with chimeric antigen receptor T-cell therapy for hematologic malignancies. Conclusions and Relevance Microbes in the gut and other locations in the body may influence the development and progression of cancer and may affect the response to adverse effects from cancer therapy. Future therapies targeting microbes in the gut and other locations in the body could potentially improve outcomes in patients with cancer.
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Affiliation(s)
- Estefania Fernandez
- Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston
| | - Jennifer A Wargo
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston
| | - Beth A Helmink
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
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Zhang WL, Yu LP, Zhou W, Wang X, Du J. Exploring the oral bacteria-oral lichen planus connection: mechanisms, clinical implications and future directions. Arch Microbiol 2025; 207:143. [PMID: 40353891 DOI: 10.1007/s00203-025-04342-y] [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: 03/19/2025] [Revised: 04/15/2025] [Accepted: 04/25/2025] [Indexed: 05/14/2025]
Abstract
Oral lichen planus (OLP) is a prevalent T-cell mediated inflammatory-immune disease with uncertain etiology. Recently, there is emerging evidence suggesting that oral bacteria may exert a prominent role in the onset and development of OLP. They might promote the initiation and progression of OLP by disrupting the oral epithelia, invading the lamina propria, stimulating pro-inflammatory cytokines production and inducing immune dysfunction. In this review, we will focus on the possible mechanisms of oral bacteria contributing to occurrence and development of OLP, and provide new insights into the bacteria-related diagnosis, prevention and treatment strategies for OLP.
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Affiliation(s)
- Wei-Long Zhang
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- School of Stomatology, Shandong First Medical University, Jinan, China
| | - Lian-Pin Yu
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Wei Zhou
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xue Wang
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- School of Stomatology, Shandong First Medical University, Jinan, China
| | - Juan Du
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
- School of Stomatology, Shandong First Medical University, Jinan, China.
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Anton L, Cristancho AG, Ferguson B, Ravel J, Elovitz MA. Cervicovaginal microbiome alters transcriptomic and epigenomic signatures across cervicovaginal epithelial barriers. RESEARCH SQUARE 2025:rs.3.rs-6171614. [PMID: 40386438 PMCID: PMC12083688 DOI: 10.21203/rs.3.rs-6171614/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/25/2025]
Abstract
Background The cervicovaginal microbiome plays a critical role in women's health, with microbial communities dominated by Lactobacillus species considered optimal. In contrast, the depletion of lactobacilli and the presence of a diverse array of strict and facultative anaerobes, such as Gardnerella vaginalis, have been linked with adverse reproductive outcomes. Despite these associations, the molecular mechanisms by which host-microbial interactions modulate cervical and vaginal epithelial function remains poorly understood. Results In this study, we used RNA sequencing to characterize the transcriptional response of cervicovaginal epithelial cells exposed to the culture supernatants of common vaginal bacteria. Our findings revealed that G. vaginalis culture supernatants upregulate genes associated with an activated innate immune response and increased cell death. Conversely, Lactobacillus crispatus culture supernatants induced transcriptional changes indicative of epigenomic modeling in ectocervical epithelial cells. Epigenomic modification by L. crispatus, was confirmed by ATAC-sequencing, which demonstrated reduced chromatin accessibility. Conclusions These results provide new insights into host-microbe interactions within the lower reproductive tract and suggests that modulating the vaginal microbiome could offer innovative therapeutic strategies to improve reproductive health.
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Origüela V, Lopez-Zaplana A. Gut Microbiota: An Immersion in Dysbiosis, Associated Pathologies, and Probiotics. Microorganisms 2025; 13:1084. [PMID: 40431257 PMCID: PMC12113704 DOI: 10.3390/microorganisms13051084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Revised: 04/29/2025] [Accepted: 05/05/2025] [Indexed: 05/29/2025] Open
Abstract
The importance of the microbiome, particularly the gut microbiota and its implications for health, is well established. However, an increasing number of studies further strengthen the link between an imbalanced gut microbiota and a greater predisposition to different diseases. The gut microbiota constitutes a fundamental ecosystem for maintaining human health. Its alteration, known as dysbiosis, is associated with a wide range of conditions, including intestinal, metabolic, immunological, or neurological pathologies, among others. In recent years, there has been a substantial increase in knowledge about probiotics-bacterial species that enhance health or address various diseases-with numerous studies reporting their benefits in preventing or improving these conditions. This review aims to analyze the most common pathologies resulting from an imbalance in the gut microbiota, as well as detail the most important and known gut probiotics, their functions, and mechanisms of action in relation to these conditions.
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Affiliation(s)
- Valentina Origüela
- Department of Physiology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain;
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Jiang WH, Zhao XW, Jin XM, Wang WJ, Chen Z. Mixed Infections in the Female Lower Genital Tract: Unlocking the Current Landscape and Future Directions. Curr Med Sci 2025:10.1007/s11596-025-00058-8. [PMID: 40327219 DOI: 10.1007/s11596-025-00058-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 04/15/2025] [Accepted: 04/17/2025] [Indexed: 05/07/2025]
Abstract
Understanding mixed infections in the female lower genital tract is a critical challenge in modern infection research. The interplay of multiple pathogens complicates disease progression, often resulting in treatment failure, recurrent infections, and significant public health and economic burdens. These infections are further exacerbated by disrupted host immune responses, which hinder the recovery of the vaginal microecosystem. Additionally, microbial biofilms-a fundamental mode of pathogen coexistence-contribute to the persistence and drug resistance of these infections, complicating management strategies. This review examines the pathogenesis, diagnosis, and treatment of mixed infections in the female lower genital tract while exploring potential avenues for future research. These findings emphasize the need for greater focus on these infections and offer insights to enhance further research in this area.
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Affiliation(s)
- Wen-Hua Jiang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xin-Wei Zhao
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xi-Ming Jin
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Wen-Jia Wang
- Department of Child Healthcare, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Zhuo Chen
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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