Gut Microbes最新文献

{"title":"Seasonal variations in circulating endocannabinoidome mediators and gut microbiota composition in humans.","authors":"Sophie Castonguay-Paradis, Élisabeth Demers-Potvin, Gabrielle Rochefort, Sébastien Lacroix, Julie Perron, Cyril Martin, Nicolas Flamand, Frédéric Raymond, Vincenzo Di Marzo, Alain Veilleux","doi":"10.1080/19490976.2025.2476563","DOIUrl":"10.1080/19490976.2025.2476563","url":null,"abstract":"<p><strong>Background: </strong>The human gut microbiome-endocannabinoidome axis is crucial for several homeostatic processes, including inflammation and energy metabolism, and is influenced by many endogenous and exogenous factors, such as dietary habits. Changes in the gut microbiome in response to seasonal variations were previously reported and tentatively attributed to shifts in dietary patterns. However, there is a need for longitudinal studies in industrialized populations to comprehensively explore seasonal variations independently of lifestyle confounding factors.</p><p><strong>Objective: </strong>To investigate the longitudinal effects of seasonal variations on the composition of the gut microbiome and the circulating levels of endocannabinoidome mediators in humans, while elucidating the contributing factors underlying these changes.</p><p><strong>Methods: </strong>Plasma and fecal samples were collected at the end of both the winter and summer in a longitudinal cohort of 48 individuals living in Québec City (Canada). Dietary habits, medical history, fecal microbiota taxonomic composition and plasma levels of circulating <i>N‑</i>acyl‑ethanolamines (NAEs) and 2<i>‑</i>monoacyl-glycerols (2<i>‑</i>MAGs) were obtained at each time point.</p><p><strong>Results: </strong>Lower circulating levels of most NAEs were observed at the end of summer. These changes were accompanied by a reduction in the relative abundance of the <i>Bifidobacteriaceae</i> and <i>Lachnospiraceae</i> families, along with an increase in the abundance of the <i>Bacteroidaceae</i> and <i>Ruminococcaceae</i> families. These seasonal variations were not associated with concurrent changes in adiposity parameters, dietary intakes, physical activity habits, or vitamin D status. Importantly, the magnitude of the shift in gut microbiota composition from winter to summer was found to be associated with the seasonal variations in circulating endocannabinoidome (eCBome) mediators.</p><p><strong>Conclusion: </strong>This study identified specific seasonal changes in gut microbiota composition and circulating levels of several NAEs, which were not associated with vitamin D status and lifestyle habits. It underscores the importance of the gut microbiota-endocannabinoidome axis in the pathophysiology of seasonal changes, and of considering seasons in clinical trials on these systems.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2476563"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial succinate promotes the response to metformin by upregulating secretory immunoglobulin a in intestinal immunity.","authors":"Ying Zhang, Aiting Wang, Wei Zhao, Jia'an Qin, Yu Zhang, Bing Liu, Chengcheng Yao, Jianglan Long, Mingxia Yuan, Dan Yan","doi":"10.1080/19490976.2025.2450871","DOIUrl":"10.1080/19490976.2025.2450871","url":null,"abstract":"<p><p>Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus; however, many patients respond poorly to this drug in clinical practice. The potential involvement of microbiota-mediated intestinal immunity and related signals in metformin responsiveness has not been previously investigated. In this study, we successfully constructed a humanized mouse model by fecal transplantation of the gut microbiota from clinical metformin-treated - responders and non-responders, and reproduced the difference in clinical phenotypes of responsiveness to metformin. The abundance of <i>Bacteroides thetaiotaomicron</i>, considered a representative differential bacterium of metformin responsiveness, and the level of secretory immunoglobulin A (SIgA) in intestinal immunity increased significantly in responder recipient mice following metformin treatment. In contrast, no significant alterations in <i>B. thetaiotaomicron</i> and SIgA were observed in non-responder recipient mice. The study of IgA^-/- mice confirmed that downregulated expression or deficiency of SIgA resulted in non-response to metformin, meaning that metformin was unable to improve dysfunctional glucose metabolism and reduce intestinal and adipose tissue inflammation, ultimately leading to systemic insulin resistance. Furthermore, supplementation with succinate, a microbial product of <i>B. thetaiotaomicron</i>, potentially reversed the non-response to metformin by inducing the production of SIgA. In conclusion, we demonstrated that upregulated SIgA, which could be regulated by succinate, was functionally involved in metformin response through its influence on immune cell-mediated inflammation and insulin resistance. Conversely, an inability to regulate SIgA may result in a lack of response to metformin.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2450871"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased dietary protein stimulates amino acid catabolism via the gut microbiota and secondary bile acid production.","authors":"Sandra Tobón-Cornejo, Monica Sanchez-Tapia, Rocio Guizar-Heredia, Laura Velázquez Villegas, Lilia G Noriega, Janette Furuzawa-Carballeda, Rogelio Hernández-Pando, Natalia Vázquez-Manjarrez, Omar Granados-Portillo, Adriana López-Barradas, Rosa Rebollar-Vega, Otoniel Maya, Aaron W Miller, Aurora Serralde, Martha Guevara-Cruz, Nimbe Torres, Armando R Tovar","doi":"10.1080/19490976.2025.2465896","DOIUrl":"10.1080/19490976.2025.2465896","url":null,"abstract":"<p><p>Excess amino acids from a protein-rich diet are mainly catabolized in the liver. However, it is still unclear to what extent the gut microbiota may be involved in the mechanisms governing this catabolism. Therefore, the aim of this study was to investigate whether consumption of different dietary protein concentrations induces changes in the taxonomy of the gut microbiota, which may contribute to the regulation of hepatic amino acid catabolism. Consumption of a high-protein diet caused overexpression of HIF-1α in the colon and increase in mitochondrial activity, creating a more anaerobic environment that was associated with changes in the taxonomy of the gut microbiota promoting an increase in the synthesis of secondary bile acids, increased secretion of pancreatic glucagon. This effect was demonstrated in pancreatic islets, where secondary bile acids stimulated the expression of the PC2 enzyme that promotes glucagon formation. The increase in circulating glucagon was associated with an induction of the expression of hepatic amino acid-degrading enzymes, an effect attenuated by antibiotics. Thus, high protein intake in mice and humans induced the increase of different species in the gut microbiota with the capacity to produce secondary bile acids leading to an increase in secondary bile acids and glucagon levels, promoting amino acid catabolism.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2465896"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/19490976.2025.2471120","DOIUrl":"10.1080/19490976.2025.2471120","url":null,"abstract":"","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2471120"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolism.","authors":"Andrea Fumagalli, Anna Castells-Nobau, Dakshat Trivedi, Josep Garre-Olmo, Josep Puig, Rafel Ramos, Lluís Ramió-Torrentà, Vicente Pérez-Brocal, Andrés Moya, Jonathan Swann, Elena Martin-Garcia, Rafael Maldonado, José Manuel Fernández-Real, Jordi Mayneris-Perxachs","doi":"10.1080/19490976.2025.2455506","DOIUrl":"10.1080/19490976.2025.2455506","url":null,"abstract":"<p><p>The relationship between bacteria, cognitive function and obesity is well established, yet the role of archaeal species remains underexplored. We used shotgun metagenomics and neuropsychological tests to identify microbial species associated with cognition in a discovery cohort (IRONMET, <i>n</i> = 125). Interestingly, methanogen archaeas exhibited the strongest positive associations with cognition, particularly <i>Methanobrevibacter smithii</i> (<i>M. smithii</i>). Stratifying individuals by median-centered log ratios (CLR) of <i>M. smithii</i> (low and high <i>M. smithii</i> groups: LMs and HMs) revealed that HMs exhibited better cognition and distinct gut bacterial profiles (PERMANOVA <i>p</i> = 0.001), characterized by increased levels of Verrucomicrobia, Synergistetes and Lentisphaerae species and reduced levels of Bacteroidetes and Proteobacteria. Several of these species were linked to the cognitive test scores. These findings were replicated in a large-scale validation cohort (Aging Imageomics, <i>n</i> = 942). Functional analyses revealed an enrichment of energy, butyrate, and bile acid metabolism in HMs in both cohorts. Global plasma metabolomics by CIL LC-MS in IRONMET identified an enrichment of methylhistidine, phenylacetate, alpha-linolenic and linoleic acid, and secondary bile acid metabolism associated with increased levels of 3-methylhistidine, phenylacetylgluamine, adrenic acid, and isolithocholic acid in the HMs group. Phenylacetate and linoleic acid metabolism also emerged in the Aging Imageomics cohort performing untargeted HPLC-ESI-MS/MS metabolic profiling, while a targeted bile acid profiling identified again isolithocholic acid as one of the most significant bile acid increased in the HMs. 3-Methylhistidine levels were also associated with intense physical activity in a second validation cohort (IRONMET-CGM, <i>n</i> = 116). Finally, FMT from HMs donors improved cognitive flexibility, reduced weight, and altered SCFAs, histidine-, linoleic acid- and phenylalanine-related metabolites in the dorsal striatum of recipient mice. <i>M. smithii</i> seems to interact with the bacterial ecosystem affecting butyrate, histidine, phenylalanine, and linoleic acid metabolism with a positive impact on cognition, constituting a promising therapeutic target to enhance cognitive performance, especially in subjects with obesity.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2455506"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay of m6A RNA methylation and gut microbiota in modulating gut injury.","authors":"Haixia Wang, Juanjuan Han, Xin-An Zhang","doi":"10.1080/19490976.2025.2467213","DOIUrl":"10.1080/19490976.2025.2467213","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2467213"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-restricted feeding promotes glucagon-like peptide-1 secretion and regulates appetite via tryptophan metabolism of gut <i>Lactobacillus</i> in pigs.","authors":"Qiuke Li, Ding Tan, Shijie Xiong, Kaifan Yu, Yong Su, Weiyun Zhu","doi":"10.1080/19490976.2025.2467185","DOIUrl":"10.1080/19490976.2025.2467185","url":null,"abstract":"<p><p>Previous clinical trials have shown that time-restricted feeding can be involved in regulating the metabolic health of humans and animals. However, the underlying mechanism has not been fully explored. In this study, the pig model was employed to simulate four prevalent human eating habits, with the aim of investigating the impact of gut microbiota and microbial metabolites on gut hormone secretion and appetite regulation. Compared to the <i>ad libitum</i> feeding (ALF) pattern, three time-restricted feeding patterns reduced total food intake and eating time. Meanwhile, three time-restricted feeding patterns induced elevated levels of serum and hypothalamic glucagon-like peptide-1 (GLP-1), while suppressing reward-related circuits in the hypothalamus. It is noteworthy that the early time-restricted feeding (eTRF) pattern increased the number of intestinal enteroendocrine cells (EECs) compared to ALF. Metagenomic and metabonomic analyses revealed that three time-restricted feeding patterns induced colonization of <i>Lactobacillus</i> and significantly increased the levels of its metabolite, indole-3-lactic acid (ILA). Dietary supplementation with ILA exhibited an increasing trend in fasting serum GLP-1 level of piglets. <i>In vitro</i> studies with pig intestinal organoids showed the <i>Lactobacillus</i> metabolite ILA enhanced GLP-1 secretion through the promotion of intestinal stem cell differentiation into EECs, rather than activating the ability of EECs to secrete GLP-1. Overall, time-restricted feeding promoted GLP-1 secretion and affected long-term appetite regulation by promoting the colonization of <i>Lactobacillus</i> and modulating microbial tryptophan metabolism.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2467185"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIIST305 mitigates gastrointestinal acute radiation syndrome injury and ameliorates radiation-induced gut microbiome dysbiosis.","authors":"Debmalya Mitra, Gabriel K Armijo, Elizabeth H Ober, Shenda M Baker, Helen C Turner, Constantinos G Broustas","doi":"10.1080/19490976.2025.2458189","DOIUrl":"10.1080/19490976.2025.2458189","url":null,"abstract":"<p><p>High-dose radiation exposure results in gastrointestinal (GI) acute radiation syndrome identified by the destruction of mucosal layer, intestinal growth barrier dysfunction, and aberrant inflammatory responses. Further, radiation causes gut microbiome dysbiosis characterized by diminished microbial diversity, mostly commensal bacteria, and the spread of bacterial pathogens that trigger the recruitment of immune cells and the production of pro-inflammatory factors that lead to further GI tissue damage. Currently, there are no U.S. Food and Drug Administration (FDA) approved countermeasures that can treat radiation-induced GI injuries. To meet this critical need, Synedgen Inc. has developed a glycopolymer radiomitigator (MIIST305) that is specifically targeted to the GI tract, which acts by intercalating into the mucus layer and the glycocalyx of intestinal epithelial cells that could potentially ameliorate the deleterious effects of radiation. Male C57BL/6J adult mice were exposed to 13 Gy partial body X-irradiation with 5% bone marrow shielding and MIIST305 was administered on days 1, 3, and 5 post-irradiation. Approximately 85% of the animals survived the irradiation exposure and were apparently healthy until the end of the 30-day study period. In contrast, no control, Vehicle-treated animals survived past day 10 at this radiation dose. We show that MIIST305 improved intestinal epithelial barrier function and suppressed systemic inflammatory responses mediated by radiation-induced pro-inflammatory cytokines. Taxonomic profiling and community structure of the fecal and colonic mucosa microbiota demonstrated that MIIST305 treatment increased microbial diversity and restored abundance of beneficial commensal bacteria, including <i>Lactobacillus</i> and <i>Bifidobacterium</i> genera while suppressing potentially pathogenic bacteria <i>Enterococcus</i> and <i>Staphylococcus</i> compared with Vehicle-treated animals. In summary, MIIST305 is a novel GI-targeted therapeutic that greatly enhances survival in mice exposed to lethal radiation and protects the GI tract from injury by restoring a balanced gut microbiota and reducing pro-inflammatory responses. Further development of this drug as an FDA-approved medical countermeasure is of critical importance.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2458189"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The global stress response regulator <i>oxyS</i> in an adherent-invasive <i>Escherichia coli</i> strain attenuates experimental colitis.","authors":"Diana Arsene, Sandrine Y Tchaptchet, Jonathan J Hansen","doi":"10.1080/19490976.2025.2473518","DOIUrl":"10.1080/19490976.2025.2473518","url":null,"abstract":"<p><p>Crohn's disease and ulcerative colitis in humans and experimental immune-mediated colitis in mice are likely due in part to overactive immune responses to resident intestinal bacteria, including certain strains of adherent-invasive <i>Escherichia coli</i> (<i>E. coli</i>) such as <i>E. coli</i> NC101. We have previously shown that specific <i>E. coli</i> NC101 stress responses are upregulated during experimental colitis and attenuate inflammation. However, the roles of broader stress response pathways in <i>E. coli</i> NC101 during experimental colitis are unknown. We hypothesize that the global stress response regulator in <i>E. coli</i>, <i>oxyS</i>, also reduces experimental colitis. We show that intestinal <i>E. coli</i> NC101 upregulate <i>oxyS</i> expression during colitis in monocolonized interleukin-10 deficient mice. Furthermore, we demonstrate that <i>oxyS</i>-sufficient <i>E. coli</i> NC101 have decreased motility and biofilm formation <i>in vitro</i> and attenuated intestinal translocation and colitogenic potential <i>in</i> <i>vivo</i> compared with <i>oxyS-</i>deficient <i>E. coli</i>. These data suggest that activation of a generalized <i>E. coli</i> stress response, <i>oxyS</i>, reduces experimental colitis and may be a potential therapeutic target.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2473518"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiota and metabolite-based prediction tool for colonic polyposis with and without a known genetic driver.","authors":"Bryson W Katona, Ashutosh Shukla, Weiming Hu, Thomas Nyul, Christina Dudzik, Alex Arvanitis, Daniel Clay, Michaela Dungan, Marina Weber, Vincent Tu, Fuhua Hao, Shuheng Gan, Lillian Chau, Anna M Buchner, Gary W Falk, David L Jaffe, Gregory Ginsberg, Suzette N Palmer, Xiaowei Zhan, Andrew D Patterson, Kyle Bittinger, Josephine Ni","doi":"10.1080/19490976.2025.2474141","DOIUrl":"10.1080/19490976.2025.2474141","url":null,"abstract":"<p><p>Despite extensive investigations into the microbiome and metabolome changes associated with colon polyps and colorectal cancer (CRC), the microbiome and metabolome profiles of individuals with colonic polyposis, including those with (Gene-pos) and without (Gene-neg) a known genetic driver, remain comparatively unexplored. Using colon biopsies, polyps, and stool from patients with Gene-pos adenomatous polyposis (<i>N</i> = 9), Gene-neg adenomatous polyposis (<i>N</i> = 18), and serrated polyposis syndrome (SPS, <i>N</i> = 11), we demonstrated through 16S rRNA sequencing that the mucosa-associated microbiota in individuals with colonic polyposis is representative of the microbiota associated with small polyps, and that both Gene-pos and SPS cohorts exhibit differential microbiota populations relative to Gene-neg polyposis cohorts. Furthermore, we used these differential microbiota taxa to perform linear discriminant analysis to differentiate Gene-neg subjects from Gene-pos and from SPS subjects with an accuracy of 89% and 93% respectively. Stool metabolites were quantified via ¹H NMR, revealing an increase in alanine in SPS subjects relative to non-polyposis subjects, and Partial Least Squares Discriminant Analysis (PLS-DA) analysis indicated that the proportion of leucine to tyrosine in fecal samples may be predictive of SPS. Use of these microbial and metabolomic signatures may allow for better diagnostric and risk-stratification tools for colonic polyposis patients and their families as well as promote development of microbiome-targeted approaches for polyp prevention.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2474141"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}