Gut Microbes最新文献

{"title":"Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine.","authors":"Izabella Sall, Randi Foxall, Lindsey Felth, Soren Maret, Zachary Rosa, Anirudh Gaur, Jennifer Calawa, Nadia Pavlik, Jennifer L Whistler, Cheryl A Whistler","doi":"10.1080/19490976.2024.2446423","DOIUrl":"10.1080/19490976.2024.2446423","url":null,"abstract":"<p><p>The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2446423"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970564","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>In vitro</i> competition with <i>Bifidobacterium</i> strains impairs potentially pathogenic growth of <i>Clostridium perfringens</i> on 2'-fucosyllactose.","authors":"Aruto Nakajima, Aleksandr A Arzamasov, Mikiyasu Sakanaka, Ryuta Murakami, Tomoya Kozakai, Keisuke Yoshida, Toshihiko Katoh, Miriam N Ojima, Junko Hirose, Saeko Nagao, Jin-Zhong Xiao, Toshitaka Odamaki, Dmitry A Rodionov, Takane Katayama","doi":"10.1080/19490976.2025.2478306","DOIUrl":"10.1080/19490976.2025.2478306","url":null,"abstract":"<p><p>Fortifying infant formula with human milk oligosaccharides, such as 2'-fucosyllactose (2'-FL), is a global trend. Previous studies have shown the inability of pathogenic gut microbes to utilize 2'-FL. However, the present study demonstrates that the type strain (JCM 1290^T) of <i>Clostridium perfringens</i>, a pathobiont species often more prevalent and abundant in the feces of C-section-delivered infants, exhibits potentially pathogenic growth on 2'-FL. The expression of genes for α-toxin, an activator of NLRP3 inflammasome, and ethanolamine ammonia-lyase, a factor responsible for the progression of gas gangrene, was significantly upregulated during 2'-FL assimilation compared to growth on lactose. However, colony-forming unit of <i>C. perfringens</i> JCM 1290^T markedly decreased when co-cultivated with selected strains of <i>Bifidobacterium</i>, a taxon frequently detected in the breastfed infant gut. Moreover, during co-cultivation, the expression of virulence-related genes, including the gene for perfringolysin O - another activator of NLRP3 inflammasome - were significantly downregulated, while the lactate oxidation genes were upregulated. This can occur through two different mechanisms: direct competition for 2'-FL between the two organisms, or cross-feeding of lactose, released from 2'-FL by <i>C. perfringens</i> JCM 1290^T, to <i>Bifidobacterium</i>. Attenuation of α-toxin production by the selected <i>Bifidobacterium</i> strains was observed to varying extents in 2'-FL-utilizing <i>C. perfringens</i> strains clinically isolated from healthy infants. Our results warrant detailed <i>in vivo</i> studies using animal models with dysbiotic microbiota dominated by various types of <i>C. perfringens</i> strains to further validate the safety of 2'-FL for clinical interventions, particularly on vulnerable preterm infants.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2478306"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657014","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":"AhR Activation Transcriptionally Induces Anti-Microbial Peptide Alpha-Defensin 1 Leading to Reversal of Gut Microbiota Dysbiosis and Colitis.","authors":"Manikandan Palrasu, Khadija Kakar, Amarnath Marudamuthu, Hamida Hamida, Shruthi Thada, Yin Zhong, Shanieka Staley, Philip Brandon Busbee, Jie Li, Monica Garcia-Buitrago, Mitzi Nagarkatti, Prakash Nagarkatti","doi":"10.1080/19490976.2025.2460538","DOIUrl":"10.1080/19490976.2025.2460538","url":null,"abstract":"<p><p>Alpha-defensin 1 is a small antimicrobial peptide that acts as the first line of defense against pathogens. It is induced following microbial cues and inflammatory signals in neutrophils and Paneth cells in the small intestine, which suggests that it plays a role in microbial homeostasis in the gut. The gut microbial products also serve as ligands for the aryl hydrocarbon receptor (AhR), an environmental sensor. In the current study, we investigated if there is any crosstalk between AhR and alpha-defensin 1. Interestingly, we found a positive correlation between AhR and alpha-defensin 1 protein levels in ileal tissues from active Crohn's' (CD) patients and epithelial cells (IECs) from multiple models of murine colitis. <i>In vitro</i> downregulation of AhR led to inhibition of α-defensin 1, while activation of AhR induced α-defensin 1 in IECs. AhR directly targeted the dioxin response element 3 (DRE3) region on the α-defensin 1 promoter in IECs. AhR-mediated induction of α-defensin 1 in colitis mice reversed the gut microbial dysbiosis and alleviated colitis. Our data identify a novel signaling pathway in which AhR acts as a transcription factor for α-defensin 1, leading to regulation of homeostasis between gut microbiota, intestinal mucosa, and mucosal immunity.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2460538"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079035","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":"Mucus-penetrating microbiota drive chronic low-grade intestinal inflammation and metabolic dysregulation.","authors":"Melissa C Kordahi, Noëmie Daniel, Andrew T Gewirtz, Benoit Chassaing","doi":"10.1080/19490976.2025.2455790","DOIUrl":"10.1080/19490976.2025.2455790","url":null,"abstract":"<p><p>Metabolic syndrome is, in humans, associated with alterations in the composition and localization of the intestinal microbiota, including encroachment of bacteria within the colon's inner mucus layer. Possible promoters of these events include dietary emulsifiers, such as carboxymethylcellulose (CMC) and polysorbate-80 (P80), which, in mice, result in altered microbiota composition, encroachment, low-grade inflammation and metabolic syndrome. While assessments of gut microbiota composition have largely focused on fecal/luminal samples, we hypothesize an outsized role for changes in mucus microbiota in driving low-grade inflammation and its consequences. In support of this notion, we herein report that both CMC and P80 led to stark changes in the mucus microbiome, markedly distinct from those observed in feces. Moreover, transfer of mucus microbiota from CMC- and P80-fed mice to germfree mice resulted in microbiota encroachment, low-grade inflammation, and various features of metabolic syndrome. Thus, we conclude that mucus-associated bacteria are pivotal determinants of intestinal inflammatory tone and host metabolism.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2455790"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046572","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":"Indole derivatives ameliorated the methamphetamine-induced depression and anxiety via aryl hydrocarbon receptor along \"microbiota-brain\" axis.","authors":"Xi Wang, Miaoyang Hu, Weilan Wu, Xinyu Lou, Rong Gao, Tengfei Ma, S Thameem Dheen, Jie Cheng, Jianping Xiong, Xufeng Chen, Jun Wang","doi":"10.1080/19490976.2025.2470386","DOIUrl":"10.1080/19490976.2025.2470386","url":null,"abstract":"<p><p>In addition to the high neurotoxicity, depression, and anxiety are the most prominent characteristics of methamphetamine (Meth) withdrawal. Studies to date on the issue of Meth-associated depression and anxiety are focused on the brain, however, whether peripheral homeostasis, especially the \"microbiota-gut\" axis participates in these adverse outcomes, remains poorly understood. In the current study, with the fecal microbiota transplantation (FMT) assay, the mice received microbiota from Meth withdrawal mice displayed marked depression and anxiety behaviors. The 16S rRNA sequencing results showed that Meth withdrawal contributed to a striking reduction of <i>Akkermansia, Bacteroides, Faecalibaculum, Desulfovibrio, and Anaerostipes</i>, which are known to be associated with tryptophan (TRP) metabolism. Noteworthily, the substantial decreases of the indole derivatives from the TRP metabolic pathway, including IAA, IPA, ILA, IET, IArA, IAld, and TRM were observed in the serum of both Meth abusing humans and mice during Meth withdrawal with the UHPLC-MS/MS analysis. Combining the high and low TRP diet mouse model, the mice with high TRP diet obviously impeded Meth-associated depression and anxiety behaviors, and these results were further strengthened by the evidence that administration of IPA, IAA, and indole dramatically ameliorated the Meth induced aberrant behaviors. Importantly, these protective effects were remarkably counteracted in aryl hydrocarbon receptor knockout (AhR KO) mice, underlining the key roles of microbiota-indoles-AhR signaling in Meth-associated depression and anxiety. Collectively, the important contribution of the present work is that we provide the first evidence that peripheral gut homeostasis disturbance but not limited to the brain, plays a key role in driving the Meth-induced depression and anxiety in the periods of withdrawal, especially the microbiota and the indole metabolic disturbance. Therefore, targeting AhR may provide novel insight into the therapeutic strategies for Meth-associated psychological disorders.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2470386"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491811","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":"Exploring the mechanism of intestinal bacterial translocation after severe acute pancreatitis: the role of Toll-like receptor 5.","authors":"Cheng Zhang, Shiyin Chen, Zhien Wang, Jian Zhang, Wenqiao Yu, Yanshuai Wang, Weiwei Si, Yuwei Zhang, Yun Zhang, Tingbo Liang","doi":"10.1080/19490976.2025.2489768","DOIUrl":"https://doi.org/10.1080/19490976.2025.2489768","url":null,"abstract":"<p><p>Severe acute pancreatitis (SAP)-induced intestinal bacterial translocation and enterogenic infection are among the leading causes of mortality in patients. However, the mechanisms by which SAP disrupted the intestinal barrier and led to bacterial translocation remained unclear. Therefore, we employed multi-omics analysis including microbiome, metabolome, epigenome, transcriptome, and mass cytometry (CyTOF) to identify potential targets, followed by functional validation using transgenic mice. The integrated multi-omics analysis primarily indicated overgrowth of intestinal flagellated bacteria, upregulation of intestinal Toll-like receptor 5 (TLR5) and acute inflammatory response, and increased infiltration of intestinal high-expressing TLR5 lamina propria dendritic cells (TLR5^hi LPDC) after SAP. Subsequently, intestinal flagellin-TLR5 signaling was activated after SAP. Intestinal barrier disruption, bacterial translocation, and helper T cells (Th) differentiation imbalance caused by SAP were alleviated in TLR5 knocked out (<i>Tlr5</i>^-/-) or conditionally knocked out on LPDC (<i>Tlr5</i>^ΔDC) mice. However, TLR5 conditional knockout on intestinal epithelial cells (<i>Tlr5</i>^ΔIEC) failed to improve SAP-induced bacterial translocation. Moreover, depletion of LPDC and regulatory T cells (Treg) ameliorated bacterial translocation after SAP. Our findings identify TLR5 on LPDC as a potential novel target for preventing or treating intestinal bacterial translocation caused by SAP.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2489768"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964258","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":"Human microbiota influence the immune cell composition and gene expression in the tumor environment of a murine model of glioma.","authors":"George B H Green, Alexis N Cox-Holmes, Gillian H Marlow, Anna Claire E Potier, Yong Wang, Lianna Zhou, Dongquan Chen, Casey D Morrow, Braden C McFarland","doi":"10.1080/19490976.2025.2508432","DOIUrl":"https://doi.org/10.1080/19490976.2025.2508432","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has shown success against other cancers but not glioblastoma. Previous data has revealed that microbiota influences anti-PD-1 efficacy. We have previously found that, when using gnotobiotic mice transplanted with human fecal microbiota, the gut microbial composition influenced the response to anti-PD-1 in a mouse model of glioma. However, the role of the human microbiota in influencing the mouse immune cells in the glioma microenvironment and anti-PD-1 response was largely unknown. Using two distinct humanized microbiome (HuM) lines, we used single-cell RNA sequencing (scRNA-seq) to determine how gut microbiota affect immune infiltration and gene expression in a murine glioma model.</p><p><strong>Methods: </strong>16S rRNA sequencing was performed on fecal samples from HuM1 (H1) and HuM2 (H2) mice. Mice were intracranially injected with murine glioma cells (GL261), and on day 13 treated with one dose of isotype control or anti-PD1. Mice were euthanized on day 14 for analysis of all immune cells in the tumors by scRNA-seq.</p><p><strong>Results: </strong>HuM1 and HuM2 mice had different microbial populations, with HuM1 being primarily dominated via <i>Alistipes</i>, and HuM2 being primarily composed of <i>Odoribacter</i>. Sc-RNA-seq of the tumor immune cells revealed 21 clusters with significant differences between H1 and H2 samples with a larger population of M1 type macrophages in H1 samples. Gene expression analysis revealed higher expression of inflammatory markers in the M1 population in H2 mice treated with anti-PD-1.</p><p><strong>Conclusions: </strong>Microbial gut communities influence the presence and gene activation patterns of immune cells in the brain tumors of mice both under control (isotype) and following anti-PD-1 treatment.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2508432"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181788","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":"Faecal metaproteomics analysis reveals a high cardiovascular risk profile across healthy individuals and heart failure patients.","authors":"Chaoran Yang, Leticia Camargo Tavares, Han-Chung Lee, Joel R Steele, Rosilene V Ribeiro, Anna L Beale, Stephanie Yiallourou, Melinda J Carrington, David M Kaye, Geoffrey A Head, Ralf B Schittenhelm, Francine Z Marques","doi":"10.1080/19490976.2024.2441356","DOIUrl":"https://doi.org/10.1080/19490976.2024.2441356","url":null,"abstract":"<p><p>The gut microbiota is a crucial link between diet and cardiovascular disease (CVD). Using fecal metaproteomics, a method that concurrently captures human gut and microbiome proteins, we determined the crosstalk between gut microbiome, diet, gut health, and CVD. Traditional CVD risk factors (age, BMI, sex, blood pressure) explained < 10% of the proteome variance. However, unsupervised human protein-based clustering analysis revealed two distinct CVD risk clusters (low-risk and high-risk) with different blood pressure (by 9 mmHg) and sex-dependent dietary potassium and fiber intake. In the human proteome, the low-risk group had lower angiotensin-converting enzymes, inflammatory proteins associated with neutrophil extracellular trap formation and auto-immune diseases. In the microbial proteome, the low-risk group had higher expression of phosphate acetyltransferase that produces SCFAs, particularly in fiber-fermenting bacteria. This model identified severity across phenotypes in heart failure patients and long-term risk of cardiovascular events in a large population-based cohort. These findings underscore multifactorial gut-to-host mechanisms that may underlie risk factors for CVD.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2441356"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871925","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":"Bacteriophage-driven DNA inversions shape bacterial functionality and long-term co-existence in <i>Bacteroides fragilis</i>.","authors":"Shaqed Carasso, Roni Keshet-David, Jia Zhang, Haitham Hajjo, Dana Kadosh-Kariti, Tal Gefen, Naama Geva-Zatorsky","doi":"10.1080/19490976.2025.2501492","DOIUrl":"https://doi.org/10.1080/19490976.2025.2501492","url":null,"abstract":"<p><p>Bacterial genomic DNA inversions, which govern molecular phase-variations, provide the bacteria with functional plasticity and phenotypic diversity. These targeted rearrangements enable bacteria to respond to environmental challenges, such as bacteriophage predation, evading immune detection or gut colonization. This study investigated the short- and long-term effects of the lytic phage Barc2635 on the functional plasticity of <i>Bacteroides fragilis</i>, a gut commensal. Germ-free mice were colonized with <i>B. fragilis</i> and exposed to Barc2635 to identify genomic alterations driving phenotypic changes. Phage exposure triggered dynamic and prolonged bacterial responses, including significant shifts in phase-variable regions (PVRs), particularly in promoter orientations of polysaccharide biosynthesis loci. These shifts coincided with increased entropy in PVR inversion ratios, reflecting heightened genomic variability. In contrast, <i>B. fragilis</i> in control mice exhibited stable genomic configurations after gut adaptation. The phase-variable Type 1 restriction-modification system, which affects broad gene expression patterns, showed variability in both groups. However, phage-exposed bacteria displayed more restrained variability, suggesting phage-derived selection pressures. Our findings reveal that <i>B. fragilis</i> employs DNA inversions to adapt rapidly to phage exposure and colonization, highlighting a potential mechanism by which genomic variability contributes to its response to phage. This study demonstrates gut bacterial genomic and phenotypic plasticity upon exposure to the mammalian host and to bacteriophages.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2501492"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994588","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":"Integrating multi-omics data to reveal the host-microbiota interactome in inflammatory bowel disease.","authors":"Fengyuan Su, Meng Su, Wenting Wei, Jiayun Wu, Leyan Chen, Xiqiao Sun, Moyan Liu, Shiqiang Sun, Ren Mao, Arno R Bourgonje, Shixian Hu","doi":"10.1080/19490976.2025.2476570","DOIUrl":"10.1080/19490976.2025.2476570","url":null,"abstract":"<p><p>Numerous studies have accelerated the knowledge expansion on the role of gut microbiota in inflammatory bowel disease (IBD). However, the precise mechanisms behind host-microbe cross-talk remain largely undefined, due to the complexity of the human intestinal ecosystem and multiple external factors. In this review, we introduce the <i>interactome</i> concept to systematically summarize how intestinal dysbiosis is involved in IBD pathogenesis in terms of microbial composition, functionality, genomic structure, transcriptional activity, and downstream proteins and metabolites. Meanwhile, this review also aims to present an updated overview of the relevant mechanisms, high-throughput multi-omics methodologies, different types of multi-omics cohort resources, and computational methods used to understand host-microbiota interactions in the context of IBD. Finally, we discuss the challenges pertaining to the integration of multi-omics data in order to reveal host-microbiota cross-talk and offer insights into relevant future research directions.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2476570"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596839","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}