Gut Microbes最新文献

{"title":"The gut microbiota: an emerging modulator of drug resistance in hepatocellular carcinoma.","authors":"Jiali Yao, Beifang Ning, Jin Ding","doi":"10.1080/19490976.2025.2473504","DOIUrl":"10.1080/19490976.2025.2473504","url":null,"abstract":"<p><p>Liver cancer is usually diagnosed at an advanced stage and is the third most common cause of cancer-related death worldwide. In addition to the lack of effective treatment options, resistance to therapeutic drugs is a major clinical challenge. The gut microbiota has recently been recognized as one of the key factors regulating host health. The microbiota and its metabolites can directly or indirectly regulate gene expression in the liver, leading to gut-liver axis dysregulation, which is closely related to liver cancer occurrence and the treatment response. Gut microbiota disturbance may participate in tumor progression and drug resistance through metabolite production, gene transfer, immune regulation, and other mechanisms. However, systematic reviews on the role of the gut microbiota in drug resistance in liver cancer are lacking. Herein, we review the relationships between the gut microbiota and the occurrence and drug resistance of hepatocellular carcinoma, summarize the emerging mechanisms underlying gut microbiota-mediated drug resistance, and propose new personalized treatment options to overcome this resistance.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2473504"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556252","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 insights into carbohydrate utilisation, antimicrobial resistance, and sporulation potential in <i>Roseburia intestinalis</i> isolates across diverse geographical locations.","authors":"Indrani Mukhopadhya, Jennifer C Martin, Sophie Shaw, Martin Gutierrez-Torrejon, Nikoleta Boteva, Aileen J McKinley, Silvia W Gratz, Karen P Scott","doi":"10.1080/19490976.2025.2473516","DOIUrl":"10.1080/19490976.2025.2473516","url":null,"abstract":"<p><p><i>Roseburia intestinalis</i> is one of the most abundant and important butyrate-producing human gut anaerobic bacteria that plays an important role in maintaining health and is a potential next-generation probiotic. We investigated the pangenome of 16 distinct strains, isolated over several decades, identifying local and time-specific adaptations. More than 50% of the genes in each individual strain were assigned to the core genome, and 77% of the cloud genes were unique to individual strains, revealing the high level of genome conservation. Co-carriage of the same enzymes involved in carbohydrate binding and degradation in all strains highlighted major pathways in carbohydrate utilization and reveal the importance of xylan, starch and mannose as key growth substrates. A single strain had adapted to use rhamnose as a sole growth substrate, the first time this has been reported. The ubiquitous presence of motility and sporulation gene clusters demonstrates the importance of these phenotypes for gut survival and acquisition of this bacterium. More than half the strains contained functional, potentially transferable, tetracycline resistance genes. This study advances our understanding of the importance of <i>R. intestinalis</i> within the gut ecosystem by elucidating conserved metabolic characteristics among different strains, isolated from different locations. This information will help to devise dietary strategies to increase the abundance of this species providing health benefits.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2473516"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633873","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":"Long-term yogurt intake and colorectal cancer incidence subclassified by <i>Bifidobacterium</i> abundance in tumor.","authors":"Satoko Ugai, Li Liu, Keisuke Kosumi, Hidetaka Kawamura, Tsuyoshi Hamada, Kosuke Mima, Kota Arima, Kazuo Okadome, Qian Yao, Kosuke Matsuda, Yuxue Zhong, Hiroki Mizuno, Andrew T Chan, Wendy S Garrett, Mingyang Song, Marios Giannakis, Edward L Giovannucci, Xuehong Zhang, Shuji Ogino, Tomotaka Ugai","doi":"10.1080/19490976.2025.2452237","DOIUrl":"10.1080/19490976.2025.2452237","url":null,"abstract":"<p><p>Evidence suggests a tumor-suppressive effect of the intake of yogurt, which typically contains <i>Bifidobacterium</i>. We hypothesized that long-term yogurt intake might be associated with colorectal cancer incidence differentially by tumor subgroups according to the amount of tissue <i>Bifidobacterium</i>. We utilized the prospective cohort incident-tumor biobank method and resources of two prospective cohort studies. Inverse probability weighted multivariable Cox proportional hazards regression was used to assess differential associations of yogurt intake with the incidence of colorectal carcinomas subclassified by the abundance of tumor tissue <i>Bifidobacterium</i>. During follow-up of 132,056 individuals, we documented 3,079 incident colorectal cancer cases, including 1,121 with available tissue <i>Bifidobacterium</i> data. The association between long-term yogurt intake and colorectal cancer incidence differed by <i>Bifidobacterium</i> abundance (P heterogeneity = 0.0002). Multivariable-adjusted hazard ratios (HRs) (with 95% confidence intervals) in individuals who consumed ≥2 servings/week (vs. <1 serving/month) of yogurt were 0.80 (0.50-1.28) for <i>Bifidobacterium</i>-positive tumor and 1.09 (0.81-1.46) for <i>Bifidobacterium</i>-negative tumor. This differential association was also observed in a subgroup analysis of proximal colon cancer (P heterogeneity = 0.018). Long-term yogurt intake may be differentially associated with the incidence of proximal colon cancer according to <i>Bifidobacterium</i> abundance, suggesting the antitumor effect of yogurt intake on the specific tumor subgroup.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2452237"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398876","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":"Metaproteomics reveals age-specific alterations of gut microbiome in hamsters with SARS-CoV-2 infection.","authors":"Marybeth Creskey, Fabiola Silva Angulo, Qing Wu, Levi Tamming, Emily E F Fekete, Kai Cheng, Zhibin Ning, Angela Wang, Patrícia Brito Rodrigues, Vinícius de Rezende Rodovalho, Marco Aurélio Ramirez Vinolo, Daniel Figeys, Xuguang Li, Francois Trottein, Xu Zhang","doi":"10.1080/19490976.2025.2505117","DOIUrl":"10.1080/19490976.2025.2505117","url":null,"abstract":"<p><p>The gut microbiome's pivotal role in health and disease is well established. SARS-CoV-2 infection often causes gastrointestinal symptoms and is associated with changes of the microbiome in both human and animal studies. While hamsters serve as important animal models for coronavirus research, there exists a notable void in the functional characterization of their microbiomes with metaproteomics. In this study, we present a workflow for analyzing the hamster gut microbiome, including a metagenomics-derived hamster gut microbial protein database and a data-independent acquisition metaproteomics method. Using this workflow, we identified 32,419 protein groups from the fecal microbiomes of young and old hamsters infected with SARS-CoV-2. We showed age-specific changes in the expressions of microbiome functions and host proteins associated with microbiomes, providing further functional insight into the interactions between the microbiome and host in SARS-CoV-2 infection. Altogether, this study established and demonstrated the capability of metaproteomics for the study of hamster microbiomes.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2505117"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127494","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>Lachnospiraceae bacterium</i> alleviates alcohol-associated liver disease by enhancing N-acetyl-glutamic acid levels and inhibiting ferroptosis through the KEAP1-NRF2 pathway.","authors":"Hejiao Zhang, Qiang Hu, Yong Zhang, Lei Yang, Shanfei Tian, Xinru Zhang, Haiyuan Shen, Hang Shu, Linxi Xie, Dongqing Wu, Liangliang Zhou, Xiaoli Wei, Chen Cheng, Jiali Jiang, Hua Wang, Cailiang Shen, Derun Kong, Long Xu","doi":"10.1080/19490976.2025.2517821","DOIUrl":"10.1080/19490976.2025.2517821","url":null,"abstract":"<p><p>Alcohol-associated liver disease (ALD) is a prevalent global health issue primarily caused by excessive alcohol consumption. Recent studies have highlighted the gut-liver axis's protective role against ALD, mainly through gut microbiota. However, the precise mechanism remains ill-defined. Our results showed a significant reduction in <i>Lachnospiraceae bacterium</i> in the gut microbiota of ALD patients and ethanol (EtOH)-fed mice, as revealed by 16S rDNA sequencing. Supplementation with <i>Lachnospiraceae bacterium</i> strains in mice significantly reduced inflammation, hepatic neutrophil infiltration, oxidative stress, and improved gut microbiota and intestinal permeability. Multi-omics analysis identified N-Acetyl-glutamic acid (NAG) as the most significantly altered metabolite following <i>Lachnospiraceae bacterium</i> supplementation, with levels positively correlated to <i>Lachnospiraceae bacterium</i> colonization. NAG treatment exhibited significant protective effects in EtOH-exposed hepatocyte cell lines and EtOH-fed mice. Mechanistically, NAG confers hepatoprotection against ALD by activating the KEAP1-NRF2 pathway, inhibiting ferroptosis. Notably, the protective effects of NAG were reversed by the NRF2 inhibitor. In conclusion, oral supplementation with <i>Lachnospiraceae bacterium</i> mitigates alcohol-induced liver damage both <i>in vivo</i> and <i>in vitro</i> by inhibiting ferroptosis through NAG-mediated activation of the KEAP1-NRF2 pathway. <i>Lachnospiraceae bacterium</i> may serve as promising probiotics for future clinical applications.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2517821"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283551","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 microbial metabolite butyrate suppresses hepatocellular carcinoma growth via CXCL11-dependent enhancement of natural killer cell infiltration.","authors":"Menghan Zhang, Xuefeng Huang, Yanlong Zhang, Minghang Yu, Xiaoxue Yuan, Yifan Xu, Lei Ma, Xi Wang, Huichun Xing","doi":"10.1080/19490976.2025.2519706","DOIUrl":"https://doi.org/10.1080/19490976.2025.2519706","url":null,"abstract":"<p><p>Gut microbiota-derived butyrate plays a vital role in attenuating hepatocellular carcinoma (HCC) in murine models. However, the precise molecular mechanisms by which butyrate exerts its effects are largely undefined. Plasma short-chain fatty acids (SCFAs) were quantitatively measured by using gas chromatography-mass spectrometry (GC-MS) to access their association with HCC prognosis. Tumor-infiltrating immune cells were characterized by flow cytometry. The interactions between butyrate and natural killer (NK) cells were studied using in vitro assays, including migration, cytotoxic degranulation, and co-culture experiments. In vivo validation was conducted through neutralization experiments. The molecular pathways regulated by butyrate were further investigated by employing RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq). A positive correlation was observed between elevated plasma butyrate levels and improved prognosis in HCC patients. Notably, butyrate inhibited tumor progression by enhancing NK cell infiltration into tumor tissues. Mechanistically, butyrate stimulated cytokine secretion, notably significantly enhancing the production of the chemokine CXCL11, thereby facilitating NK cell infiltration. Gene Set Enrichment Analysis (GSEA) of hepatic tumor cell lines revealed that the chemokine signaling and NK cell-mediated cytotoxicity pathways were upregulated following butyrate stimulation. Furthermore, transcriptomic and epigenomic analyses showed that exposure to butyrate induced de novo chromatin accessibility and enhancer remodeling, regulated by STAT family transcription factors. Our study demonstrated that butyrate was able to enhance the expression of CXCL11. This is likely attributed to chromatin remodeling, and then promoting NK cell infiltration and exerting effective anti-tumor effects on HCC.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2519706"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505550","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":"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}