Gut Microbes最新文献

{"title":"Multifunctional dietary approach reduces intestinal inflammation in relation with changes in gut microbiota composition in subjects at cardiometabolic risk: the SINFONI project.","authors":"Hugo Hornero-Ramirez, Arianne Morisette, Bruno Marcotte, Armelle Penhoat, Béryle Lecomte, Baptiste Panthu, Jacob Lessard Lord, Florence Thirion, Laurie Van-Den-Berghe, Emilie Blond, Chantal Simon, Cyrielle Caussy, Nathalie Feugier, Joël Doré, Philippe Sanoner, Alexandra Meynier, Yves Desjardins, Geneviève Pilon, André Marette, Patrice D Cani, Martine Laville, Sophie Vinoy, Marie-Caroline Michalski, Julie-Anne Nazare","doi":"10.1080/19490976.2024.2438823","DOIUrl":"10.1080/19490976.2024.2438823","url":null,"abstract":"<p><p>The development of cardiometabolic (CM) diseases is associated with chronic low-grade inflammation, partly linked to alterations of the gut microbiota (GM) and reduced intestinal integrity. The SINFONI project investigates a multifunctional (MF) nutritional strategy's impact combining different bioactive compounds on inflammation, GM modulation and CM profile. In this randomized crossover-controlled study, 30 subjects at CM-risk consumed MF cereal-products, enriched with polyphenols, fibers, slowly-digestible starch, omega-3 fatty acids or Control cereal-products (without bioactive compounds) for 2 months. Metabolic endotoxemia (lipopolysaccharide (LPS), lipopolysaccharide-binding protein over soluble cluster of differentiation-14 (LBP/sCD14), systemic inflammation and cardiovascular risk markers, intestinal inflammation, CM profile and response to a one-week fructose supplementation, were assessed at fasting and post mixed-meal. GM composition and metabolomic analysis were conducted. Mixed linear models were employed, integrating time (pre/post), treatment (MF/control), and sequence/period. Compared to control, MF intervention reduced intestinal inflammation (fecal calprotectin, <i>p</i> = 0.007) and endotoxemia (fasting LPS, <i>p</i> < 0.05), without alteration of systemic inflammation. MF decreased serum branched-chain amino acids compared to control (<i>p</i> < 0.05) and increased <i>B.ovatus</i>, <i>B.uniformis</i>, <i>A.butyriciproducens</i> and unclassified <i>Christensenellaceae.CAG-74</i> (<i>p</i> < 0.05). CM markers were unchanged. A 2-month dietary intervention combining multiple bioactive compounds improved intestinal inflammation and induced GM modulation. Such strategy appears as an effective strategy to target low-grade inflammation through multi-target approach.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2438823"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876914","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":"Alterations in mucosa branched <i>N</i>-glycans lead to dysbiosis and downregulation of ILC3: a key driver of intestinal inflammation.","authors":"Cláudia S Rodrigues, Joana Gaifem, Márcia S Pereira, Maria Francisca Alves, Mariana Silva, Nuno Padrão, Bruno Cavadas, Catarina Moreira-Barbosa, Inês Alves, Ricardo Marcos-Pinto, Joana Torres, Aonghus Lavelle, Jean-Frederic Colombel, Harry Sokol, Salomé S Pinho","doi":"10.1080/19490976.2025.2461210","DOIUrl":"10.1080/19490976.2025.2461210","url":null,"abstract":"<p><p>The perturbation of the symbiotic relationship between microbes and intestinal immune system contributes to gut inflammation and Inflammatory Bowel Disease (IBD) development. The host mucosa glycans (glycocalyx) creates a major biological interface between gut microorganisms and host immunity that remains ill-defined. Glycans are essential players in IBD immunopathogenesis, even years before disease onset. However, how changes in mucosa glycosylation shape microbiome and how this impact gut immune response and inflammation remains to be clarified. Here, we revealed that alterations in the expression of complex branched <i>N</i>-glycans at gut mucosa surface, modeled in glycoengineered mice, resulted in dysbiosis, with a deficiency in Firmicutes bacteria. Concomitantly, this mucosa <i>N</i>-glycan switch was associated with a downregulation of type 3 innate lymphoid cells (ILC3)-mediated immune response, leading to the transition of ILC3 toward an ILC1 proinflammatory phenotype and increased TNFα production. In addition, we demonstrated that the mucosa glycosylation remodeling through prophylactic supplementation with glycans at steady state was able to restore microbial-derived short-chain fatty acids and microbial sensing (by <i>NOD2</i> expression) alongside the rescue of the expression of ILC3 module, suppressing intestinal inflammation and controlling disease onset. In a complementary approach, we further showed that IBD patients, often displaying dysbiosis, exhibited a tendency of decreased <i>MGAT5</i> expression at epithelial cells that was accompanied by reduced ILC3 expression in gut mucosa. Altogether, these results unlock the effects of alterations in mucosa glycome composition in the regulation of the bidirectional crosstalk between microbiota and gut immune response, revealing host branched <i>N</i>-glycans/microbiota/ILC3 axis as an essential pathway in gut homeostasis and in preventing health to intestinal inflammation transition.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2461210"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364643","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":"<i>Helicobacter pylori</i> infection induces DNA double-strand breaks through the ACVR1/IRF3/POLD1 signaling axis to drive gastric tumorigenesis.","authors":"Xinbo Xu, Xiao Fei, Huan Wang, Xidong Wu, Yuan Zhan, Xin Li, Yan'an Zhou, Chunxi Shu, Cong He, Yi Hu, Jianping Liu, Nonghua Lv, Nianshuang Li, Yin Zhu","doi":"10.1080/19490976.2025.2463581","DOIUrl":"10.1080/19490976.2025.2463581","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> (<i>H. pylori</i>) infection plays a pivotal role in gastric carcinogenesis through inflammation-related mechanisms. Activin A receptor type I (ACVR1), known for encoding the type I receptor for bone morphogenetic proteins (BMPs), has been identified as a cancer diver gene across various tumors. However, the specific role of AVCR1 in <i>H. pylori</i>-induced gastric tumorigenesis remains incompletely understood. We conducted a comprehensive analysis of the clinical relevance of ACVR1 by integrating data from public databases and our local collection of human gastric tissues. In vitro cell cultures, patient-derived gastric organoids, and transgenic INS-GAS mouse models were used for Western blot, qRT-PCR, immunofluorescence, immunohistochemistry, luciferase assays, ChIP, and comet assays. Furthermore, to investigate the therapeutic potential, we utilized the ACVR1 inhibitor DM3189 in our in vivo studies. <i>H. pylori</i> infection led to increased expression of ACVR1 in gastric epithelial cells, gastric organoid and gastric mucosa of INS-GAS mice. ACVR1 activation led to DNA double-strand break (DSB) accumulation by inhibiting POLD1, a crucial DNA repair enzyme. The activation of POLD1 was facilitated by the transcription factor IRF3, with identified binding sites. Additionally, treatment with the ACVR1 inhibitor DM3189 significantly ameliorated <i>H. pylori</i>-induced gastric pathology and reduced DNA damage in INS-GAS mice. Immunohistochemistry analysis showed elevated levels of ACVR1 in <i>H. pylori</i>-positive gastritis tissues, showing a negative correlation with POLD1 expression. This study uncovers a novel signaling axis of AVCR1/IRF3/POLD1 in the pathogenesis of <i>H. pylori</i> infection. The upregulation of ACVR1 and the suppression of POLD1 upon <i>H. pylori</i> infection establish a connection between the infection, genomic instability, and the development of gastric carcinogenesis.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2463581"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382298","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":"<i>Lactobacillus intestinalis</i> facilitates tumor-derived CCL5 to recruit dendritic cell and suppress colorectal tumorigenesis.","authors":"Yong Sun, Qiwen Wang, Yao Jiang, Jiamin He, Dingjiacheng Jia, Man Luo, Wentao Shen, Qingyi Wang, Yadong Qi, Yifeng Lin, Ying Zhang, Lan Wang, Liangjing Wang, Shujie Chen, Lina Fan","doi":"10.1080/19490976.2024.2449111","DOIUrl":"10.1080/19490976.2024.2449111","url":null,"abstract":"<p><p>Gut microbes play a crucial role in regulating the tumor microenvironment (TME) of colorectal cancer (CRC). Nevertheless, the deep mechanism between the microbiota-TME interaction has not been well explored. In this study, we for the first time discovered that <i>Lactobacillus intestinalis</i> (<i>L. intestinalis</i>) effectively suppressed tumor growth both in the AOM/DSS-induced CRC model and the <i>Apc</i>^Min/+ spontaneous adenoma model. Our investigation revealed that <i>L. intestinalis</i> increased the infiltration of immune cells, particularly dendritic cells (DC), in the TME. Mechanically, the tumor-derived CCL5 induced by <i>L. intestinalis</i> recruited DC chemotaxis through the NOD1/NF-κB signaling pathway. In clinical samples and datasets, we found positive correlation between <i>L. intestinalis</i>, CCL5 level, and the DC-related genes. Our study provided a new strategy for microbial intervention for CRC and deepened the understanding of the interaction between tumor cells and the immune microenvironment modulated by gut microbes.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2449111"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947795","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":"Mouse strain-specific responses along the gut-brain axis upon fecal microbiota transplantation from children with autism.","authors":"Naika Prince, Lucia N Peralta Marzal, Léa Roussin, Magali Monnoye, Catherine Philippe, Elise Maximin, Sabbir Ahmed, Karoliina Salenius, Jake Lin, Reija Autio, Youri Adolfs, R Jeroen Pasterkamp, Johan Garssen, Laurent Naudon, Sylvie Rabot, Aletta D Kraneveld, Paula Perez-Pardo","doi":"10.1080/19490976.2024.2447822","DOIUrl":"10.1080/19490976.2024.2447822","url":null,"abstract":"<p><p>Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD. Briefly, we depleted the microbiota of conventional male BALB/cAnNCrl (Balb/c) and C57BL/6J (BL/6) mice prior to human fecal microbiota transplantation (hFMT) with samples from children with ASD or their neurotypical siblings. We found mouse strain-specific responses to ASD hFMT. Notably, Balb/c mice exhibit decreased exploratory and social behavior, and show evidence of intestinal, systemic, and central inflammation accompanied with metabolic shifts. BL/6 mice show less changes after hFMT. Our results reveal that gut microbiota alone induce changes in ASD-like behavior, and highlight the importance of mouse strain selection when investigating multifactorial conditions like ASD.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2447822"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947805","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":"T cells regulate intestinal motility and shape enteric neuronal responses to intestinal microbiota.","authors":"Patricia Rodrigues Marques de Souza, Catherine M Keenan, Laurie E Wallace, Yasaman Bahojb Habibyan, Marcela Davoli-Ferreira, Christina Ohland, Fernando A Vicentini, Kathy D McCoy, Keith A Sharkey","doi":"10.1080/19490976.2024.2442528","DOIUrl":"https://doi.org/10.1080/19490976.2024.2442528","url":null,"abstract":"<p><p>How the gut microbiota and immune system maintain intestinal homeostasis in concert with the enteric nervous system (ENS) remains incompletely understood. To address this gap, we assessed small intestinal transit, enteric neuronal density, enteric neurogenesis, intestinal microbiota, immune cell populations and cytokines in wildtype and T-cell deficient germ-free mice colonized with specific pathogen-free (SPF) microbiota, conventionally raised SPF and segmented filamentous bacteria (SFB)-monocolonized mice. SPF microbiota increased small intestinal transit in a T cell-dependent manner. SPF microbiota increased neuronal density in the myenteric and submucosal plexuses of the ileum and colon, similar to conventionally raised SPF mice, independently of T cells. SFB increased neuronal density in the ileum in a T cell-dependent manner, but independently of T cells in the colon. SPF microbiota stimulated enteric neurogenesis (Sox2 expression in enteric neurons) in the ileum in a T cell-dependent manner, but in the colon this effect was T cell-independent. T cells regulated nestin expression in the ENS. SPF colonization increased Th17 cells, RORγT⁺ Treg cells, and IL-1β and IL-17A levels in the ileum and colon. By neutralizing IL-1β and IL-17A, we observed that they control microbiota-mediated enteric neurogenesis but were not involved in the regulation of motility. Together, these findings provide new insights into the microbiota-neuroimmune dialog that regulates intestinal physiology.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2442528"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863988","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":"Gut microbiota and microbial metabolites for osteoporosis.","authors":"Xuan-Qi Zheng, Ding-Ben Wang, Yi-Rong Jiang, Chun-Li Song","doi":"10.1080/19490976.2024.2437247","DOIUrl":"10.1080/19490976.2024.2437247","url":null,"abstract":"<p><p>Osteoporosis is an age-related bone metabolic disease. As an essential endocrine organ, the skeletal system is intricately connected with extraosseous organs. The crosstalk between bones and other organs supports this view. In recent years, the link between the gut microecology and bone metabolism has become an important research topic, both in preclinical studies and in clinical trials. Many studies have shown that skeletal changes are accompanied by changes in the composition and structure of the gut microbiota (GM). At the same time, natural or artificial interventions targeting the GM can subsequently affect bone metabolism. Moreover, microbiome-related metabolites may have important effects on bone metabolism. We aim to review the relationships among the GM, microbial metabolites, and bone metabolism and to summarize the potential mechanisms involved and the theory of the gut‒bone axis. We also describe existing bottlenecks in laboratory studies, as well as existing challenges in clinical settings, and propose possible future research directions.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2437247"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846350","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":"<i>Fusobacterium sphaericum</i> sp. nov., isolated from a human colon tumor adheres to colonic epithelial cells and induces IL-8 secretion.","authors":"Martha A Zepeda-Rivera, Yannick Eisele, Alexander Baryiames, Hanrui Wu, Claudia Mengoni, Gianmarco Piccinno, Elsa F McMahon, Kaitlyn D LaCourse, Dakota S Jones, Hans Hauner, Samuel S Minot, Nicola Segata, Floyd E Dewhirst, Christopher D Johnston, Susan Bullman","doi":"10.1080/19490976.2024.2442522","DOIUrl":"https://doi.org/10.1080/19490976.2024.2442522","url":null,"abstract":"<p><p>Cancerous tissue is a largely unexplored microbial niche that provides a unique environment for the colonization and growth of specific bacterial communities, and with it, the opportunity to identify novel bacterial species. Here, we report distinct features of a novel <i>Fusobacterium</i> species, <i>F.</i> <i>sphaericum</i> sp. nov. (<i>Fs</i>), isolated from primary colon adenocarcinoma tissue. We acquire the complete closed genome and associated methylome of this organism and phylogenetically confirm its classification into the <i>Fusobacterium</i> genus, with <i>F. perfoetens</i> as its closest neighbor. <i>Fs</i> is phenotypically and genetically distinct, with morphological analysis revealing its coccoid shape, that while similar to <i>F. perfoetens</i> is rare for most <i>Fusobacterium</i> members. <i>Fs</i> displays a metabolic profile and antibiotic resistance repertoire consistent with other <i>Fusobacterium</i> species. <i>In vitro, Fs</i> has adherent and immunomodulatory capabilities, as it intimately associates with human colon cancer epithelial cells and promotes IL-8 secretion. An analysis of the prevalence and abundance of <i>Fs</i> in > 20,000 human metagenomic samples shows that it is a rarely detected member within human stool with variable relative abundance, found in both healthy controls and patients with colorectal cancer (CRC). Our study sheds light on a novel bacterial species isolated directly from the human CRC tumor niche and given its <i>in</i> <i>vitro</i> interaction with cancer epithelial cells suggests that its role in human health and disease warrants further investigation.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2442522"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894076","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":"Mucosal washes are useful for sampling intestinal mucus-associated microbiota despite low biomass.","authors":"Jennifer N Martinez-Medina, Fereshteh Ghazisaeedi, Catharina Kramer, Jörn F Ziegler, Victoria McParland, Paul W Mönch, Britta Siegmund, Víctor Hugo Jarquín-Díaz, Marcus Fulde, Sofia K Forslund-Startceva","doi":"10.1080/19490976.2025.2464296","DOIUrl":"10.1080/19490976.2025.2464296","url":null,"abstract":"<p><p>Understanding the dynamic relationship between mucus-associated microbiota and host health is critical. However, studies predominantly using stool samples may not accurately represent these bacterial communities. Here, we investigated the mucus-associated microbiota in the gastrointestinal tract of mice and the terminal ileum of humans using different sample types: mucosal washes, brushes, scrapings, and intestinal contents in mice and biopsies, brushes and mucosal washes in humans. We used DNA quantification and 16S rRNA amplicon sequencing to evaluate the comparability of the information yielded from the different sample types under a controlled benchmark. In mice, mucosal washes and brushes had comparative bacterial DNA and host DNA contamination than scraping samples. Similarly, in humans, washes outperformed biopsies in bacterial DNA content. Read counts and microbiota alpha diversity remained remarkably similar in mice and between brushes and washes in humans. The composition of the microbiota varied based on the subsegment and sample type in mice and sample type in humans. We conclude that washes and brushes reduce host contamination without inducing substantial compositional bias when sampling mucosal microbiota. Our findings suggest that mucosal washes and brushes are a viable alternative to biopsies in humans and scrapings in mice, thereby improving the transferability of results across hosts. Our study highlights the importance of focusing on mucus-associated microbiota to better capture host-microbiome interactions at their closer interface.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2464296"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467872","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":"Dysregulation of gut microbiota stimulates NETs-driven HCC intrahepatic metastasis: therapeutic implications of healthy faecal microbiota transplantation.","authors":"Zhe Deng, Si Mei, Zhaoguang Ouyang, Ruoyu Wang, Lihuai Wang, Bo Zou, Jingjing Dai, Kexin Mao, Qian Li, Qianqian Guo, Chun Yi, Fanying Meng, Mingxia Xie, Xue Zhang, Rongrong Wang, Tianhao Deng, Zhenyu Wang, Xiaozheng Li, Qing Wang, Bin Liu, Xuefei Tian","doi":"10.1080/19490976.2025.2476561","DOIUrl":"10.1080/19490976.2025.2476561","url":null,"abstract":"<p><p>The stringent regulation of intrahepatic metastases is essential for improving survival outcomes in patients with hepatocellular carcinoma (HCC). This study investigated the impact of gut microbiota on intrahepatic metastasis of HCC and evaluated the therapeutic potential of healthy fecal microbiota transplantation (FMT). Dysregulation of the gut microbiota, characterized by a significant reduction in the abundance of beneficial bacteria, such as <i>Anaerotruncus colihominis</i> and <i>Dysosmobacter welbionis</i>, was observed in patients with intrahepatic metastatic HCC. A human flora-associated (HFA) intrahepatic metastatic HCC mouse model was successfully established through consecutive 4 weeks of human-mouse FMT. Dysregulation of gut microbiota promoted intrahepatic metastasis in the mouse model, primarily by enhancing neutrophil-mediated inflammatory responses and lead to excessive formation of neutrophil extracellular traps (NETs). Consequently, it promoted tumor vascular growth and tissue necrosis, resulting in intrahepatic metastasis of HCC. Notably, FMT from healthy donors mitigated these pathological processes. This study elucidated the role and mechanism of dysregulated gut microbiota in promoting intrahepatic metastasis of HCC. Healthy FMT emerges as a promising novel therapeutic strategy for preventing and treating intrahepatic metastasis of HCC.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2476561"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657016","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}