Gut Microbes最新文献

{"title":"Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19.","authors":"Patrícia Brito Rodrigues, Vinícius de Rezende Rodovalho, Valentin Sencio, Nicolas Benech, Marybeth Creskey, Fabiola Silva Angulo, Lou Delval, Cyril Robil, Philippe Gosset, Arnaud Machelart, Joel Haas, Amandine Descat, Jean François Goosens, Delphine Beury, Florence Maurier, David Hot, Isabelle Wolowczuk, Harry Sokol, Xu Zhang, Marco Aurélio Ramirez Vinolo, François Trottein","doi":"10.1080/19490976.2025.2486511","DOIUrl":"10.1080/19490976.2025.2486511","url":null,"abstract":"<p><p>Aging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated changes in the gut microbiota from young (2-month-old) and aged (22-month-old) hamsters, a valuable model of COVID-19. We show that age-related dysfunctions in the gut microbiota are linked to disease severity and long-term sequelae in older hamsters. Our data also reveal age-specific changes in the composition and metabolic activity of the gut microbiota during both the acute phase (day 7 post-infection, D7) and the recovery phase (D22) of infection. Aged hamsters exhibited the most notable shifts in gut microbiota composition and plasma metabolic profiles. Through an integrative analysis of metagenomics, metabolomics, and clinical data, we identified significant associations between bacterial taxa, metabolites and disease markers in the aged group. On D7 (high viral load and lung epithelial damage) and D22 (body weight loss and fibrosis), numerous amino acids, amino acid-related molecules, and indole derivatives were found to correlate with disease markers. In particular, a persistent decrease in phenylalanine, tryptophan, glutamic acid, and indoleacetic acid in aged animals positively correlated with poor recovery of body weight and/or lung fibrosis by D22. In younger hamsters, several bacterial taxa (<i>Eubacterium</i>, <i>Oscillospiraceae</i>, <i>Lawsonibacter</i>) and plasma metabolites (carnosine and cis-aconitic acid) were associated with mild disease outcomes. These findings support the need for age-specific microbiome-targeting strategies to more effectively manage acute viral pneumonia and long-term disease outcomes.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2486511"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763683","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":"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":"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":"Genomic island-encoded LmiA regulates acid resistance and biofilm formation in enterohemorrhagic <i>Escherichia coli</i> O157:H7.","authors":"Hongmin Sun, Lingyan Jiang, Jingnan Chen, Chenbo Kang, Jun Yan, Shuai Ma, Mengjie Zhao, Houliang Guo, Bin Yang","doi":"10.1080/19490976.2024.2443107","DOIUrl":"10.1080/19490976.2024.2443107","url":null,"abstract":"<p><p>Enterohemorrhagic <i>Escherichia coli</i> (EHEC) O157:H7 is an important intestinal pathogen that causes severe foodborne diseases. We previously demonstrated that the genomic island-encoded regulator LmiA activates the locus of enterocyte effacement (LEE) genes to promote EHEC O157:H7 adherence and colonization in the host intestine. However, whether LmiA is involved in the regulation of any other biological processes in EHEC O157:H7 remains largely unexplored. Here, we compared global gene expression differences between the EHEC O157:H7 wild-type strain and an <i>lmiA</i> mutant strain using RNA-seq technology. Genes whose expression was affected by LmiA were identified and classified using the Cluster of Orthologous Groups (COG) database. Specifically, the expression of acid resistance genes (including <i>gadA</i>, <i>gadB</i>, and <i>gadC</i>) was significantly downregulated, whereas the transcript levels of biofilm-related genes (including <i>Z_RS00105</i>, <i>yadN</i>, <i>Z_RS03020</i>, and <i>fdeC</i>) were increased, in the Δ<i>lmiA</i> mutant compared to the EHEC O157:H7 wild-type strain. Further investigation revealed that LmiA enhanced the acid resistance of EHEC O157:H7 by directly activating the transcription of <i>gadA</i> and <i>gadBC</i>. In contrast, LmiA reduced EHEC O157:H7 biofilm formation by indirectly repressing the expression of biofilm-related genes. Furthermore, LmiA-mediated regulation of acid resistance and biofilm formation is highly conserved and widespread among EHEC and enteropathogenic <i>E. coli</i> (EPEC). Our findings provide essential insight into the regulatory function of LmiA in EHEC O157:H7, particularly its role in regulating acid resistance and biofilm formation.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2443107"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846257","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 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":"Gut microbiota modulation via fecal microbiota transplantation mitigates hyperoxaluria and calcium oxalate crystal depositions induced by high oxalate diet.","authors":"Lingyue An, Shujue Li, Zhenglin Chang, Min Lei, Zhican He, Peng Xu, Shike Zhang, Zheng Jiang, Muhammad Sarfaraz Iqbal, Xinyuan Sun, Hongxing Liu, Xiaolu Duan, Wenqi Wu","doi":"10.1080/19490976.2025.2457490","DOIUrl":"10.1080/19490976.2025.2457490","url":null,"abstract":"<p><p>Hyperoxaluria, including primary and secondary hyperoxaluria, is a disorder characterized by increased urinary oxalate excretion and could lead to recurrent calcium oxalate kidney stones, nephrocalcinosis and eventually end stage renal disease. For secondary hyperoxaluria, high dietary oxalate (HDOx) or its precursors intake is a key reason. Recently, accumulated studies highlight the important role of gut microbiota in the regulation of oxalate homeostasis. However, the underlying mechanisms involving gut microbiota and metabolite disruptions in secondary hyperoxaluria remain poorly understood. Here, we investigated the therapeutic efficacy of fecal microbiota transplantation (FMT) sourced from healthy rats fed with standard pellet diet against urinary oxalate excretion, renal damage and calcium oxalate (CaOx) crystal depositions via using hyperoxaluria rat models. We observed dose-dependent increases in urinary oxalate excretion and CaOx crystal depositions due to hyperoxaluria, accompanied by significant reductions in gut microbiota diversity characterized by shifts in <i>Ruminococcaceae_UCG-014</i> and <i>Parasutterella</i> composition. Metabolomic analysis validated these findings, revealing substantial decreases in key metabolites associated with these microbial groups. Transplanting microbes from healthy rats effectively reduced HDOx-induced urinary oxalate excretion and CaOx crystal depositions meanwhile restoring <i>Ruminococcaceae_UCG-014</i> and <i>Parasutterella</i> populations and their associated metabolites. Furthermore, FMT treatment could significantly decrease the urinary oxalate excretion and CaOx crystal depositions in rat kidneys via, at least in part, upregulating the expressions of intestinal barrier proteins and oxalate transporters in the intestine. In conclusion, our study emphasizes the effectiveness of FMT in countering HDOx-induced hyperoxaluria by restoring gut microbiota and related metabolites. These findings provide insights on the complex connection between secondary hyperoxaluria caused by high dietary oxalate and disruptions in gut microbiota, offering promising avenues for targeted therapeutic strategies.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2457490"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052280","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":"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}