Gut Microbes最新文献

{"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":"Gut microbiome-driven regulation of sex hormone homeostasis: a potential neuroendocrine connection.","authors":"Anna Clapp Organski, Bartek Rajwa, Anjali Reddivari, Joan S Jorgensen, Tzu-Wen L Cross","doi":"10.1080/19490976.2025.2476562","DOIUrl":"10.1080/19490976.2025.2476562","url":null,"abstract":"<p><p>The gut microbiome is known to have a bidirectional relationship with sex hormone homeostasis; however, its role in mediating interactions between the primary regulatory axes of sex hormones and their productions is yet to be fully understood. We utilized both conventionally raised and gnotobiotic mouse models to investigate the regulatory role of the gut microbiome on the hypothalamic-pituitary-gonadal (HPG) axis. Male and female conventionally raised mice underwent surgical modifications as follows: (1) hormonally intact controls; (2) gonadectomized males and females; (3) gonadectomized males and females supplemented with testosterone and estrogen, respectively. Fecal samples from these mice were used to colonize sex-matched, intact, germ-free recipient mice through fecal microbiota transplant (FMT). Serum gonadotropins, gonadal sex hormones, cecal microbiota, and the serum global metabolome were assessed. FMT recipients of gonadectomized-associated microbiota showed lower circulating gonadotropin levels than recipients of intact-associated microbiota, opposite to that of FMT donors. FMT recipients of gonadectomized-associated microbiota also had greater testicular weights compared to recipients of intact-associated microbiota. The gut microbiota composition of recipient mice differed significantly based on the FMT received, with the male microbiota having a more concerted impact in response to changes in the HPG axis. Network analyses showed that multiple metabolically unrelated pathways may be involved in driving differences in serum metabolites due to sex and microbiome received in the recipient mice. In sum, our findings indicate that the gut microbiome responds to the HPG axis and subsequently modulates its feedback mechanisms. A deeper understanding of interactions between the gut microbiota and the neuroendocrine-gonadal system may contribute to the development of therapies for sexually dimorphic diseases.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2476562"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604541","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":"Assessing live microbial therapeutic transmission.","authors":"Jeremiah J Faith","doi":"10.1080/19490976.2024.2447836","DOIUrl":"10.1080/19490976.2024.2447836","url":null,"abstract":"<p><p>The development of fecal microbiota transplantation and defined live biotherapeutic products for the treatment of human disease has been an empirically driven process yielding a notable success of approved drugs for the treatment of recurrent <i>Clostridioides difficile</i> infection. Assessing the potential of this therapeutic modality in other indications with mixed clinical results would benefit from consistent quantitative frameworks to characterize drug potency and composition and to assess the impact of dose and composition on the frequency and duration of strain engraftment. Monitoring these drug properties and engraftment outcomes would help identify minimally sufficient sets of microbial strains to treat disease and provide insights into the intersection between microbial function and host physiology. Broad and correct usage of strain detection methods is essential to this advancement. This article describes strain detection approaches, where they are best applied, what data they require, and clinical trial designs that are best suited to their application.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2447836"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921237","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":"Biofilm-associated proteins: from the gut biofilms to neurodegeneration.","authors":"Jaione Valle","doi":"10.1080/19490976.2025.2461721","DOIUrl":"10.1080/19490976.2025.2461721","url":null,"abstract":"<p><p>Human microbiota form a biofilm with substantial consequences for health and disease. Numerous studies have indicated that microbial communities produce functional amyloids as part of their biofilm extracellular scaffolds. The overlooked interplay between bacterial amyloids and the host may have detrimental consequences for the host, including neurodegeneration. This work gives an overview of the biofilm-associated amyloids expressed by the gut microbiota and their potential role in neurodegeneration. It discusses the biofilm-associated proteins (BAPs) of the gut microbiota, maps the amyloidogenic domains of these proteins, and analyzes the presence of <i>bap</i> genes within accessory genomes linked with transposable elements. Furthermore, the evidence supporting the existence of amyloids in the gut are presented. Finally, it explores the potential interactions between BAPs and α-synuclein, extending the literature on amyloid cross-kingdom interactions. Based on these findings, this study propose that BAP amyloids act as transmissible catalysts, facilitating the misfolding, accumulation, and spread of α-synuclein aggregates. This review contributes to the understanding of complex interactions among the microbiota, transmissible elements, and host, which is crucial for developing novel therapeutic approaches to combat microbiota-related diseases and improve overall health outcomes.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2461721"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079036","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":"The immune response modulated by inoculation of commensal bacteria at birth impacts the gut microbiota and prevents <i>Salmonella</i> colonization.","authors":"Florent Kempf, Rosanna Drumo, Anne Marie Chaussé, Pierrette Menanteau, Tereza Kubasova, Sylvie Roche, Anne Christine Lalmanach, Rodrigo Guabiraba, Thierry Chaumeil, Guillaume Larivière-Gauthier, Ignacio Caballero-Posadas, Béatrice Laroche, Ivan Rychlík, Isabelle Virlogeux-Payant, Philippe Velge","doi":"10.1080/19490976.2025.2474151","DOIUrl":"10.1080/19490976.2025.2474151","url":null,"abstract":"<p><p>Super- and low-shedding phenomena have been observed in genetically homogeneous hosts infected by a single bacterial strain. To decipher the mechanisms underlying these phenotypes, we conducted an experiment with chicks infected with <i>Salmonella</i> Enteritidis in a non-sterile isolator, which prevents bacterial transmission between animals while allowing the development of the gut microbiota. We investigated the impact of four commensal bacteria called Mix4, inoculated at hatching, on chicken systemic immune response and intestinal microbiota composition and functions, before and after <i>Salmonella</i> infection. Our results revealed that these phenotypes were not linked to changes in cell invasion capacity of bacteria during infection. Mix4 inoculation had both short- and long-term effects on immune response and microbiota and promoted the low-shedder phenotype. Kinetic analysis revealed that Mix4 activated immune response from day 4, which modified the microbiota on day 6. This change promotes a more fermentative microbiota, using the aromatic compounds degradation pathway, which inhibited <i>Salmonella</i> colonization by day 11 and beyond. In contrast, control animals exhibited a delayed TNF-driven pro-inflammatory response and developed a microbiota using anaerobic respiration, which facilitates <i>Salmonella</i> colonization and growth. This strategy offers promising opportunities to strengthen the barrier effect against <i>Salmonella</i> and possibly other pathogens.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2474151"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624416","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":"Seasonal variations in circulating endocannabinoidome mediators and gut microbiota composition in humans.","authors":"Sophie Castonguay-Paradis, Élisabeth Demers-Potvin, Gabrielle Rochefort, Sébastien Lacroix, Julie Perron, Cyril Martin, Nicolas Flamand, Frédéric Raymond, Vincenzo Di Marzo, Alain Veilleux","doi":"10.1080/19490976.2025.2476563","DOIUrl":"10.1080/19490976.2025.2476563","url":null,"abstract":"<p><strong>Background: </strong>The human gut microbiome-endocannabinoidome axis is crucial for several homeostatic processes, including inflammation and energy metabolism, and is influenced by many endogenous and exogenous factors, such as dietary habits. Changes in the gut microbiome in response to seasonal variations were previously reported and tentatively attributed to shifts in dietary patterns. However, there is a need for longitudinal studies in industrialized populations to comprehensively explore seasonal variations independently of lifestyle confounding factors.</p><p><strong>Objective: </strong>To investigate the longitudinal effects of seasonal variations on the composition of the gut microbiome and the circulating levels of endocannabinoidome mediators in humans, while elucidating the contributing factors underlying these changes.</p><p><strong>Methods: </strong>Plasma and fecal samples were collected at the end of both the winter and summer in a longitudinal cohort of 48 individuals living in Québec City (Canada). Dietary habits, medical history, fecal microbiota taxonomic composition and plasma levels of circulating <i>N‑</i>acyl‑ethanolamines (NAEs) and 2<i>‑</i>monoacyl-glycerols (2<i>‑</i>MAGs) were obtained at each time point.</p><p><strong>Results: </strong>Lower circulating levels of most NAEs were observed at the end of summer. These changes were accompanied by a reduction in the relative abundance of the <i>Bifidobacteriaceae</i> and <i>Lachnospiraceae</i> families, along with an increase in the abundance of the <i>Bacteroidaceae</i> and <i>Ruminococcaceae</i> families. These seasonal variations were not associated with concurrent changes in adiposity parameters, dietary intakes, physical activity habits, or vitamin D status. Importantly, the magnitude of the shift in gut microbiota composition from winter to summer was found to be associated with the seasonal variations in circulating endocannabinoidome (eCBome) mediators.</p><p><strong>Conclusion: </strong>This study identified specific seasonal changes in gut microbiota composition and circulating levels of several NAEs, which were not associated with vitamin D status and lifestyle habits. It underscores the importance of the gut microbiota-endocannabinoidome axis in the pathophysiology of seasonal changes, and of considering seasons in clinical trials on these systems.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2476563"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663341","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":"Upregulation of <i>Lactobacillus spp</i>. in gut microbiota as a novel mechanism for environmental eustress-induced anti-pancreatic cancer effects.","authors":"Yiyi Liang, Min Du, Xin Li, Jian Gao, Qian Li, Huimin Li, Jin Li, Xiang Gao, Hui Cong, Yimeng Huang, Xinran Li, Liwei Wang, Jiujie Cui, Yu Gan, Hong Tu","doi":"10.1080/19490976.2025.2470372","DOIUrl":"10.1080/19490976.2025.2470372","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited effective treatment options. Emerging evidence links enriched environment (EE)-induced eustress to PDAC inhibition. However, the underlying mechanisms remain unclear. In this study, we explored the role of gut microbiota in PDAC-suppressive effects of EE. We demonstrated that depletion of gut microbiota with antibiotics abolished EE-induced tumor suppression, while fecal microbiota transplantation (FMT) from EE mice significantly inhibited tumor growth in both subcutaneous and orthotopic PDAC models housed in standard environment. 16S rRNA sequencing revealed that EE enhanced gut microbiota diversity and selectively enriched probiotic <i>Lactobacillus</i>, particularly <i>L. reuteri</i>. Treatment with <i>L. reuteri</i> significantly suppressed PDAC tumor growth and increased natural killer (NK) cell infiltration into the tumor microenvironment. Depletion of NK cells alleviated the anti-tumor effects of <i>L. reuteri</i>, underscoring the essential role of NK cell-mediated immunity in anti-tumor response. Clinical analysis of PDAC patients showed that higher fecal <i>Lactobacillus</i> abundance correlated with improved progression-free and overall survival, further supporting the therapeutic potential of <i>L. reuteri</i> in PDAC. Overall, this study identifies gut microbiota as a systemic regulator of PDAC under psychological stress. Supplementation of psychobiotic <i>Lactobacillus</i> may offer a novel therapeutic strategy for PDAC.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2470372"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482959","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 dysbiosis exacerbates long-term cognitive impairments by promoting intestinal dysfunction and neuroinflammation following neonatal hypoxia-ischemia.","authors":"Andi Chen, Chengqian Teng, Jianjie Wei, Xuyang Wu, Honghong Zhang, Pinzhong Chen, Dingliang Cai, Haitao Qian, Hui Zhu, Xiaochun Zheng, Xiaohui Chen","doi":"10.1080/19490976.2025.2471015","DOIUrl":"10.1080/19490976.2025.2471015","url":null,"abstract":"<p><p>Neonatal hypoxic-ischemic brain damage (HIBD) is considered as a major cause of long-term cognitive impairments in newborns. It has been demonstrated that gut microbiota is closely associated with the prognosis of various neurological disorders. However, the role of microbiota-gut-brain axis on cognitive function following neonatal HIBD remains elusive. In this experiment, the correlation analysis supported the involvement of gut microbial changes following hypoxic-ischemic (HI) insult in the development of long-term cognitive impairments. Subsequent experiment revealed the involvement of the intestinal dysfunction in the hippocampal neuroinflammation and synaptic injury. In causal relationship validation experiments, fecal microbiota transplantation (FMT) from cognitively normal rats could restore gut microbial composition, improve intestinal dysfunction, reduce the serum levels of lipopolysaccharides (LPS) and inflammatory mediators, and alleviate neuroinflammation, synaptic damage and cognitive impairments in neonatal HIBD recipient rats. Conversely, the FMT from neonatal HIBD rats could induce above adverse pathological changes in the normal recipient rats. Moreover, oral administration of anti-inflammatory agent dexamethasone (DEX) exhibited the potential to alleviate these detrimental effects in neonatal HIBD rats, with the efficacy being partly reliant on gut microbiota. Further experiment on the potential molecular mechanisms using RNA sequencing indicated a significant increase in the toll-like receptor 4 (TLR4) gene in the intestinal tissues of neonatal HIBD rats. Additionally, the interventions such as TLR4 inhibitor TLR4-IN-C34 administration, FMT, and oral DEX were demonstrated to modulate intestinal function by inhibiting the LPS/TLR4 signaling pathway, thereby exerting neuroprotective effects. Collectively, these findings underscore the contribution of gut microbial dysbiosis post HI insult in activating the LPS/TLR4 signaling pathway, triggering intestinal inflammation and dysfunction, exacerbating systemic inflammation, and consequently worsening synaptic and cognitive impairments in neonatal HIBD rats. Hence, rectifying gut microbial dysbiosis or regulating intestinal function may represent a promising strategy for alleviating long-term cognitive impairments in neonates affected by HIBD.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2471015"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500669","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>Faecalibacterium prausnitzii</i> regulates carbohydrate metabolic functions of the gut microbiome in C57BL/6 mice.","authors":"Peiling Geng, Ni Zhao, Yufan Zhou, Reuben S Harris, Yong Ge","doi":"10.1080/19490976.2025.2455503","DOIUrl":"10.1080/19490976.2025.2455503","url":null,"abstract":"<p><p>The probiotic impact of microbes on host metabolism and health depends on both host genetics and bacterial genomic variation. <i>Faecalibacterium prausnitzii</i> is the predominant human gut commensal emerging as a next-generation probiotic. Although this bacterium exhibits substantial intraspecies diversity, it is unclear whether genetically distinct <i>F. prausnitzii</i> strains might lead to functional differences in the gut microbiome. Here, we isolated and characterized a novel <i>F. prausnitzii</i> strain (UT1) that belongs to the most prevalent but underappreciated phylogenetic clade in the global human population. Genome analysis showed that this butyrate-producing isolate carries multiple putative mobile genetic elements, a clade-specific defense system, and a range of carbohydrate catabolic enzymes. Multiomic approaches were used to profile the impact of UT1 on the gut microbiome and associated metabolic activity of C57BL/6 mice at homeostasis. Both 16S rRNA and metagenomic sequencing demonstrated that oral administration of UT1 resulted in profound microbial compositional changes including a significant enrichment of <i>Lactobacillus</i>, <i>Bifidobacterium</i>, and <i>Turicibacter</i>. Functional profiling of the fecal metagenomes revealed a markedly higher abundance of carbohydrate-active enzymes (CAZymes) in UT1-gavaged mice. Accordingly, UT1-conditioned microbiota possessed the elevated capability of utilizing starch <i>in vitro</i> and exhibited a lower availability of microbiota-accessible carbohydrates in the gut. Further analysis uncovered a functional network wherein UT1 reduced the abundance of mucin-degrading CAZymes and microbes, which correlated with a concomitant reduction of fecal mucin glycans. Collectively, our results reveal a crucial role of UT1 in facilitating the carbohydrate metabolism of the gut microbiome and expand our understanding of the genetic and phenotypic diversity of <i>F. prausnitzii</i>.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2455503"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004535","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":"Adaptations in gut Bacteroidales facilitate stable co-existence with their lytic bacteriophages.","authors":"Adrián Cortés-Martín, Colin Buttimer, Jessie L Maier, Ciara A Tobin, Lorraine A Draper, R Paul Ross, Manuel Kleiner, Colin Hill, Andrey N Shkoporov","doi":"10.1080/19490976.2025.2507775","DOIUrl":"10.1080/19490976.2025.2507775","url":null,"abstract":"<p><p>Bacteriophages (phages) and bacteria within the gut microbiome persist in long-term stable coexistence. These interactions are driven by eco-evolutionary dynamics, where bacteria employ a variety of mechanisms to evade phage infection, while phages rely on counterstrategies to overcome these defenses. Among the most abundant phages in the gut are the crAss-like phages that infect members of the order Bacteroidales, in particular, genus <i>Bacteroides</i>. In this study, we explored some of the mechanisms enabling the co-existence of four phage-Bacteroidales host pairs <i>in vitro</i> using a multi-omics approach (transcriptomics, proteomics and metabolomics). These included three <i>Bacteroides</i> species paired with three crAss-like phages (<i>Bacteroides intestinalis</i> and фcrAss001, <i>Bacteroides xylanisolvens</i> and фcrAss002, and an acapsular mutant of <i>Bacteroides thetaiotaomicron</i> with DAC15), and <i>Parabacteroides distasonis</i> paired with the siphovirus фPDS1. We show that phase variation of individual capsular polysaccharides (CPSs) is the primary mechanism promoting phage co-existence in Bacteroidales, but this is not the only strategy. Alternative resistance mechanisms, while potentially less efficient than CPS phase variation, can be activated to support bacterial survival by regulating gene expression and resulting in metabolic adaptations, particularly in amino acid degradation pathways. These mechanisms, also likely regulated by phase variation, enable bacterial populations to persist in the presence of phages, and <i>vice versa</i>. An acapsular variant of <i>B. thetaiotaomicron</i> demonstrated broader transcriptomic, proteomic, and metabolomic changes, supporting the involvement of additional resistance mechanisms beyond CPS variation. This study advances our understanding of long-term phage-host interaction, offering insights into the long-term persistence of crAss-like phages and extending these observations to other phages, such as фPDS1. Knowledge of the complexities of phage-bacteria interactions is essential for designing effective phage therapies and improving human health through targeted microbiome interventions.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2507775"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127486","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}