Gut Microbes最新文献

{"title":"Correction.","authors":"","doi":"10.1080/19490976.2026.2620281","DOIUrl":"10.1080/19490976.2026.2620281","url":null,"abstract":"","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2620281"},"PeriodicalIF":11.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12834134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040806","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":"Maternal obesity alters human milk oligosaccharides content and correlates with early acquisition of late colonizers in the neonatal gut microbiome.","authors":"Karina Corona-Cervantes, Víctor H Urrutia-Baca, July S Gámez-Valdez, Brenda Jiménez-López, Nora A Rodríguez-Gutierrez, Karla Chávez-Caraza, Francisca Espiricueta-Candelaria, Ulises A Salas Villalobos, Perla A Ramos-Parra, Janet A Gutierrez Uribe, Marion Brunck, Cristina Chuck-Hernández, Cuauhtemoc Licona-Cassani","doi":"10.1080/19490976.2025.2607043","DOIUrl":"10.1080/19490976.2025.2607043","url":null,"abstract":"<p><p>Metabolic and immune development in neonates are shaped by the succession of the gut microbiome. Maternal obesity can perturb this process by altering interactions of human milk bioactive elements, including oligosaccharides (HMOs), microbial populations, and metabolites. We conducted a longitudinal study of Mexican mother-infant dyads to examine maternal BMI-associated variations in HMOs and infant fecal microbiota. Breastmilk samples from 97 mothers were collected at 48 h, one month, and three months postpartum. We used targeted and untargeted metabolomics to profile breastmilk samples, while shotgun metagenomics was used to analyze infant fecal microbiome composition in a subset of samples. Mothers with obesity showed decreased concentration of key HMOs shortly after birth, correlating with an altered succession of their infant's gut microbiota. This included reduced early colonizers (Enterobacteriaceae) and increased abundance of intermediate and late colonizers (<i>Bifidobacterium</i> and members of the Lachnospiraceae family), over subsequent months. These taxa negatively correlated with HMOs such as 6'SL, LNnT, and LNT. Additionally, functional profiling revealed alterations in metabolic pathways related to polyamine biosynthesis, suggesting changes in microbial metabolism linked to maternal BMI. Despite the cohort's size, our study offers unique insights into the relationship between maternal obesity, HMO composition, and early infant microbial colonization in Latin-American mothers. This exploratory research serves as proof of concept, underscoring the need for larger-scale studies to validate these findings and better understand their implications for infant health. More importantly, our results highlight the interplay between maternal BMI and human milk bioactives, underscoring the importance of correlating microbial succession with maternal metabolic health to better understand early immune development in neonates.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2607043"},"PeriodicalIF":11.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970740","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":"Induction of DNA-mediated immune responses by bacterial extracellular vesicles results in control of murine norovirus infection.","authors":"Guanqi Zhao, Chanel A Mosby-Tourtellot, Javier Rosero, Alexander C Schultz, Elsa Khan, Othmane Elamrani, Mariola J Ferraro, Peter E Kima, Melissa K Jones","doi":"10.1080/19490976.2026.2624171","DOIUrl":"10.1080/19490976.2026.2624171","url":null,"abstract":"<p><p>Commensal bacteria have been a centerpiece for understanding interkingdom impacts on viral replication. Multiple groups have investigated the roles commensal bacteria played in regulating enteric virus infection and it has been found that the mechanisms through which this regulation occurs varies between the viruses and bacteria explored. For noroviruses, commensal bacteria enhance or suppress viral infection in a region-dependent manner. Recently, it was found that the extracellular vesicles (EVs) produced by commensal bacteria can suppress norovirus infection. In this study, we used murine norovirus (MNV) to probe the immunological mechanisms induced by bacterial EVs. Global analysis of gene expression pointed to induction of cytosolic DNA pathways; thus, we evaluate the DNA content packaged within the bacterial EVs and DNA-sensing pathways that activate type I interferons (IFN), including STING and TLR9. Our results showed that loss of <i>sting</i> or <i>tlr9</i>, significantly decreased IFNβ production and recovered MNV replication in the presence of bEVs. Collectively, these data demonstrated bEVs of certain gram-negative bacteria can initiate antiviral DNA-mediated type I IFN production pathways and that these pathways are involved in the suppression of MNV replication. These findings expose novel mechanisms through which the native microbiota aids the host in controlling an enteric viral infection and offers a fresh perspective on interkingdom host‒microbiota interactions.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2624171"},"PeriodicalIF":11.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124866","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":"Maternal gut microbiota mediates prenatal stress-induced fetal blood‒brain barrier dysfunction.","authors":"Xuanping Wang, Fang-Yue Zhou, Ting Wu, Chenchi Duan, Xukai Luo, Yicong Meng, He-Feng Huang, Yan-Ting Wu","doi":"10.1080/19490976.2026.2631242","DOIUrl":"10.1080/19490976.2026.2631242","url":null,"abstract":"<p><p>Maternal prenatal stress confers elevated neuropsychiatric risk to offspring, yet the mechanisms underlying fetal neurodevelopmental impairment remain elusive. The gut microbiota has emerged as a key regulator of brain development and behavior. However, the mechanisms mediating the interactions between the microbiota and the developing brain are still poorly understood. Here, utilizing a prenatal stress mouse model integrated with multi-omics approaches, comprehensive behavioral assays, and molecular validations, we demonstrate that prenatal stress not only induces maternal gut microbiota dysbiosis during pregnancy but also, more critically, leads to fetal blood‒brain barrier (BBB) developmental defects and subsequent abnormalities in emotional behavior and cognitive function in adult offspring. Maternal probiotic supplementation during gestation can reverse both gut microbial dysbiosis and fetal BBB dysfunction. Notably, transcriptomic analysis reveals that the maternal gut microbiota modulates interferon-β (IFN-β) signaling along the placenta‒fetal brain axis under stress. Furthermore, metabolomic profiling suggests that prenatal stress exposure profoundly influences the maternal fecal and serum metabolome. In conclusion, our findings establish a placenta‒brain axis wherein maternal microbial signals orchestrate fetal neurovascular development, identifying microbiota-targeted interventions as a neuroprotective strategy.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2631242"},"PeriodicalIF":11.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226545","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":"Children's gut microbiota predicts the efficacy of obesity treatment.","authors":"Mireia Alcázar, Verónica Luque, Natalia Ferré, Judit Muñoz-Hernando, Mariona Gispert-Llauradó, Ricardo Closa-Monasterolo, Albert Feliu, Gemma Castillejo, Joaquín Escribano","doi":"10.1080/19490976.2026.2631824","DOIUrl":"10.1080/19490976.2026.2631824","url":null,"abstract":"<p><strong>Background & objective: </strong>Responses to dietary interventions may vary depending on baseline gut microbiota composition. This study aimed to determine whether baseline gut microbiota diversity and composition predict the effectiveness of childhood obesity interventions.</p><p><strong>Methods: </strong>Anthropometry, triglycerides, HDL-cholesterol, HOMA-IR, and systolic and diastolic blood pressure (SBP, DBP) were evaluated and standardised in 41 children with obesity (8-14yrs). Faecal samples were collected at baseline and after one year. Intervention success was defined by improvements in metabolic risk score (MetScore) or BMI z-score. Associations between baseline microbiota features (diversity and composition) and intervention success were evaluated using Spearman's correlation and linear regression models. Gut microbiota composition and differential abundance were analyzed using ANCOM-BC2. Exploratory biomarker discovery was analyzed using LEfSe, and predictive modelling using a Random Forest (RF) classifier. Receiver operating characteristic (ROC) curve analysis was used to determine a Simpson index cut-off.</p><p><strong>Results: </strong>Higher baseline Shannon and Simpson indices, and greater abundances of <i>Faecalibacterium</i> and <i>Eubacterium coprostanoligenes</i> group, were associated with greater improvements in MetScore. <i>Faecalibacterium</i> was the most influential feature with the highest importance in the RF model, which achieved an AUC of 0.876 for MetScore and 0.873 for BMI z-score improvement. Eighty-four features differed between MetScore response groups (FDR < 0.05) with some genus-level overlap with the exploratory analysis, including <i>Eubacterium coprostanoligenes</i> and <i>Ruminococcus</i>. A Simpson index cut-off of 0.849 stratified participants high- and low-diversity groups; children above this threshold exhibited greater improvements in MetScore (<i>p</i> = 0.028), SBP (<i>p</i> = 0.043), and in HDL-cholesterol (<i>p</i> = 0.028).</p><p><strong>Conclusion: </strong>Higher baseline gut microbiota diversity and specific microbial signatures, particularly <i>Faecalibacterium</i> abundance, predicted better outcomes in childhood obesity interventions. These findings support the potential use of microbiota profiling to guide personalised treatment strategies. Further research is needed to optimise interventions.<b>Trial registration:</b> clinicaltrials.gov NCT03749291.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2631824"},"PeriodicalIF":11.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226563","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":"Gut microbiota and diet in colorectal cancer: Converging determinants of carcinogenesis.","authors":"Bhupesh Kumar Thakur, Saurav Roy Choudhury, Williams Turpin, Alberto Martin","doi":"10.1080/19490976.2026.2664684","DOIUrl":"https://doi.org/10.1080/19490976.2026.2664684","url":null,"abstract":"<p><p>Diet and the gut microbiome are major, interdependent determinants of colorectal cancer (CRC) risk. This review discusses current evidence on how dietary patterns reshape microbial ecology, modulate microbial virulence, and alter host metabolic, inflammatory, and oncogenic pathways to influence colorectal carcinogenesis. We highlight key CRC-associated microbes, including <i>pks⁺ Escherichia coli</i>, <i>Fusobacterium nucleatum</i>, enterotoxigenic <i>Bacteroides fragilis</i>, and <i>Streptococcus gallolyticus</i>, and discuss how diet governs their abundance, toxin production, and oncogenic potential. Mechanistic investigations into diet-microbe interactions reveal how pro-inflammatory, low-fiber Western-style diets foster mucosal inflammation, generation of reactive oxygen and nitrogen species, and genotoxic microbial niches, whereas fiber- and polyphenol-rich diets support protective commensals and production of anti-inflammatory metabolites. We also outline major challenges, including interindividual microbiome variability and limited translational models, and propose future directions for integrating dietary, microbial, and host-targeted strategies for CRC prevention and therapy.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2664684"},"PeriodicalIF":11.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Miniature bioreactor arrays for modeling functional and structural dysbiosis in inflammatory bowel disease.","authors":"Kira L Newman, Alexandra K Standke, Gabrielle James, Kimberly C Vendrov, Naohiro Inohara, Ingrid L Bergin, Peter D R Higgins, Krishna Rao, Vincent B Young, Nobuhiko Kamada","doi":"10.1080/19490976.2025.2604875","DOIUrl":"10.1080/19490976.2025.2604875","url":null,"abstract":"<p><p>Alterations in the gut microbiota, known as gut dysbiosis, are associated with inflammatory bowel disease (IBD). There is a need for model systems that can recapitulate the IBD gut microbiome to better understand the mechanistic impact of differences in microbiota composition and its functional consequences in a controlled laboratory setting. To this end, we introduced fecal samples from patients with Crohn's disease (CD) and ulcerative colitis (UC), as well as from healthy control subjects, to miniature bioreactor arrays (MBRAs) and analyzed the microbial communities over time. We then performed two functional assessments. First, we evaluated the colitogenic potential of the CD microbiotas in genetically susceptible germ-free IL-10-deficient mice and found that colitogenic capacity was preserved in a bioreactor-cultivated CD microbiota. Second, we tested impaired colonization resistance against <i>Clostridioides difficile</i> in UC microbiotas using the MBRA system and found that UC microbiotas were innately susceptible to <i>C. difficile</i> colonization while healthy microbiotas were resistant, consistent with what is seen clinically. Overall, our results demonstrate that IBD microbiotas perform comparably to healthy donor microbiotas in the MBRA system, successfully recapitulating microbial structure while preserving IBD-specific functional characteristics. These findings establish a foundation for further mechanistic research into the IBD microbiota using MBRAs.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2604875"},"PeriodicalIF":11.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12810045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804266","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":"Gut virome dysbiosis contributes to premature ovarian insufficiency by modulating gut bacteriome.","authors":"Jiajia Jin, Guixiang Yao, Xinjie Zhang, Tongxue Zhang, Hengbo Ye, Xiaoming Zhou, Yang Yu, Yating Zhao, Zihan Qin, Haiyan Chen, Ye Bi, Xiaowei Wang, Xiaoyu Ren, Yun Zhang, Zhe Wang, Qunye Zhang","doi":"10.1080/19490976.2025.2611645","DOIUrl":"10.1080/19490976.2025.2611645","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) significantly impairs female fertility and poses substantial health risks; however, its pathogenesis is incompletely understood, and effective therapeutic interventions are limited. Although gut bacteriome has been closely associated with ovarian dysfunction, the role and therapeutic potential of gut viruses, which far outnumber bacteria, remain largely unexplored.</p><p><strong>Results: </strong>Therefore, we recruited 60 healthy reproductive-aged women and recently diagnosed POI patients and investigated these concerns using various techniques, including whole-genome shotgun sequencing of virus-like particle (VLP) and fecal virome transplantation (FVT) in CTX-induced POI rats. We found considerable interindividual variability in the gut virome. The virome of POI patients exhibited significant dysbiosis, characterized by a marked reduction in virulent phage, significant changes in predominant phages, and a notable increase in horizontal gene transfer of resistance genes and virulence factors. Furthermore, gut VLPs from the healthy reproductive-aged women significantly improved the condition of POI rats. Conversely, gut VLPs from POI patients markedly impaired the ovarian function and reproductive capacity of healthy rats. The above regulatory effect is primarily due to modulations of gut bacteriome, specifically the estrobolome, and intestinal barrier integrity, which subsequently affect hypothalamic-pituitary-ovarian axis hormone levels and regulate ovarian oxidative stress and inflammation, thereby influencing ovarian function.</p><p><strong>Conclusions: </strong>Our findings demonstrate the critical roles of the gut virome in regulating ovarian function and provide new insights into the pathogenesis of POI. This study also underscores the therapeutic potential of the gut virome in improving ovarian dysfunction and female infertility including POI.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2611645"},"PeriodicalIF":11.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12785201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917271","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":"A novel exopolysaccharide from <i>Lactiplantibacillus plantarum</i> H6 improves cholesterol metabolism via <i>Muribaculum-</i>mediated activation of the enterohepatic FXR-FGF15 axis.","authors":"Yue Li, Jialin Wang, Hailing Wang, Xin Ma, Dayong Ren, Binghua Wang","doi":"10.1080/19490976.2026.2623578","DOIUrl":"10.1080/19490976.2026.2623578","url":null,"abstract":"<p><p>Hypercholesterolemia is a major risk factor for atherosclerotic cardiovascular disease; however, current therapeutic options such as statins are limited by issues including hepatotoxicity and patient intolerance. Probiotics and their metabolites show promise in modulating cholesterol metabolism through the gut‒liver axis, yet the specific commensal bacteria and molecular mechanisms underlying these effects remain poorly understood. In this study, we isolated and characterized EPS-D1, a novel exopolysaccharide (15.003 kDa) derived from <i>Lactiplantibacillus plantarum</i> H6, which is composed primarily of mannose (46.10%) and glucose (33.98%) and features a highly branched structure (branching degree of 29.5%). The administration of EPS-D1 significantly reduced the serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) by 40.31%, 37.55%, and 43.15%, respectively, in high-cholesterol diet (HCD) mice. Additionally, it improved hepatic steatosis and reduced markers of liver injury. Through 16S rRNA sequencing and fecal microbiota transplantation (FMT), we identified <i>Muribaculum</i> as the key commensal bacterium enriched by EPS-D1. Direct administration of <i>Muribaculum</i> (<i>Muribaculum intestinale</i>) replicated the cholesterol-lowering effects, decreasing ileal and fecal cholesterol levels by 74.79% and 53.16%, respectively. Mechanistically, both EPS-D1 and <i>M. intestinale</i> activated the enterohepatic FXR‒FGF15 axis, which resulted in the upregulation of hepatic cholesterol 7α-hydroxylase (CYP7A1) expression and the downregulation of ileal ASBT and NPC1L1, thereby promoting bile acid synthesis and inhibiting cholesterol absorption. Furthermore, <i>M. intestinale</i> increased intestinal short-chain fatty acids (SCFAs), particularly acetic acid and caproic acid, by 37.88% while also modulating the composition of the bile acid pool. These findings establish <i>M. intestinale</i> as a precise microbial target for cholesterol management and demonstrate that EPS-D1 from <i>L. plantarum</i> H6 enhances cholesterol metabolism through microbiota-mediated activation of the enterohepatic FXR‒FGF15 axis, providing a novel therapeutic strategy for managing hypercholesterolemia.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2623578"},"PeriodicalIF":11.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099619","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":"Novel bacterium <i>Enterocloster</i> sp. M3 promotes colorectal tumorigenesis via the production of the carcinogen styrene.","authors":"Yao Zeng, Yao Huang, Silin Ye, Effie Yin Tung Lau, Man Chun Chiu, Linda Fenske, Yuting Sun, Liting Jiang, Jiangying Chen, Yanqing Huang, Tingyu Zhou, Jiawei Lu, Jie Zhou, Shu Zheng, Francis Ka Leung Chan, Jessie Qiaoyi Liang","doi":"10.1080/19490976.2026.2630481","DOIUrl":"10.1080/19490976.2026.2630481","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The bacterial marker 'm3' shows promise for the non-invasive diagnosis of colorectal cancer (CRC) and adenomas. However, the m3-harboring bacterium (M3) had not been successfully cultured.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to elucidate the functional mechanisms of M3 in CRC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;M3 was isolated using a targeted enrichment strategy. Its functional roles were investigated &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. Bacterial and fecal metabolites were analyzed by untargeted LC-MS and targeted LC/GC-MS. RNA-seq profiled host gene expression altered by M3. Key enzymes were identified through whole-genome sequencing and proteomics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;M3 is phylogenetically related to &lt;i&gt;Enterocloster aldenensis&lt;/i&gt; but exhibits distinct genetic and phenotypic characteristics. M3 significantly promoted colon tumor development in both &lt;i&gt;Apc&lt;/i&gt;&lt;sup&gt;Min/+&lt;/sup&gt; mice and azoxymethane-treated mice. M3 culture supernatant enhanced colon cancer cell proliferation, migration, and cell cycle progression, accelerated xenograft tumor growth, stimulated intestinal organoid expansion, and disrupted DNA damage repair pathways. M3 produced styrene-a recognized human carcinogen-in both &lt;i&gt;in vitro&lt;/i&gt; cultures and mouse models, a function not previously reported in bacteria. Importantly, styrene levels were significantly elevated in feces of CRC patients and exceeded WHO safety limit in mouse gut (12.5 vs. 7.7 μg/kg/d). Moreover, we identified novel bacterial enzymes-aspartate ammonia-lyase and uroporphyrinogen decarboxylase-that convert phenylalanine to styrene.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study identifies M3 as a novel pro-tumorigenic bacterium in CRC, capable of direct biosynthesis of the carcinogenic metabolite styrene. We provide the first evidence of bacterial styrene biosynthesis, unveiling a previously unrecognized mechanism by which gut bacteria may promote colorectal tumorigenesis.&lt;b&gt;WHAT IS ALREADY KNOWN ON THIS TOPIC&lt;/b&gt;The bacterial marker m3 has been associated with colorectal cancer, but the bacterium carrying it had not been cultured.Styrene is a recognized environmental carcinogen linked to cancers, and its bacterial biosynthesis had not been reported.&lt;b&gt;WHAT THIS STUDY ADDS&lt;/b&gt;We isolated and characterized the novel bacterium M3, which carries the m3 marker. It is phylogenetically related to &lt;i&gt;Enterocloster aldenensis&lt;/i&gt; but possesses distinct genetic and phenotypic features.M3 promotes colorectal tumorigenesis through the production of tumor-promoting metabolites, including styrene.Fecal styrene levels are significantly elevated in colorectal cancer patients.We elucidated the mechanism of direct styrene biosynthesis in M3, identifying two novel enzymes-aspartate ammonia-lyase and uroporphyrinogen decarboxylase-that catalyze this process.&lt;b&gt;HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY&lt;/b&gt;&lt;i&gt;M3 and bacterially derived styrene may serve as novel","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2630481"},"PeriodicalIF":11.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201457","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}