Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-01-15DOI: 10.1080/19490976.2025.2450871
Ying Zhang, Aiting Wang, Wei Zhao, Jia'an Qin, Yu Zhang, Bing Liu, Chengcheng Yao, Jianglan Long, Mingxia Yuan, Dan Yan
{"title":"Microbial succinate promotes the response to metformin by upregulating secretory immunoglobulin a in intestinal immunity.","authors":"Ying Zhang, Aiting Wang, Wei Zhao, Jia'an Qin, Yu Zhang, Bing Liu, Chengcheng Yao, Jianglan Long, Mingxia Yuan, Dan Yan","doi":"10.1080/19490976.2025.2450871","DOIUrl":"10.1080/19490976.2025.2450871","url":null,"abstract":"<p><p>Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus; however, many patients respond poorly to this drug in clinical practice. The potential involvement of microbiota-mediated intestinal immunity and related signals in metformin responsiveness has not been previously investigated. In this study, we successfully constructed a humanized mouse model by fecal transplantation of the gut microbiota from clinical metformin-treated - responders and non-responders, and reproduced the difference in clinical phenotypes of responsiveness to metformin. The abundance of <i>Bacteroides thetaiotaomicron</i>, considered a representative differential bacterium of metformin responsiveness, and the level of secretory immunoglobulin A (SIgA) in intestinal immunity increased significantly in responder recipient mice following metformin treatment. In contrast, no significant alterations in <i>B. thetaiotaomicron</i> and SIgA were observed in non-responder recipient mice. The study of IgA<sup>-/-</sup> mice confirmed that downregulated expression or deficiency of SIgA resulted in non-response to metformin, meaning that metformin was unable to improve dysfunctional glucose metabolism and reduce intestinal and adipose tissue inflammation, ultimately leading to systemic insulin resistance. Furthermore, supplementation with succinate, a microbial product of <i>B. thetaiotaomicron</i>, potentially reversed the non-response to metformin by inducing the production of SIgA. In conclusion, we demonstrated that upregulated SIgA, which could be regulated by succinate, was functionally involved in metformin response through its influence on immune cell-mediated inflammation and insulin resistance. Conversely, an inability to regulate SIgA may result in a lack of response to metformin.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2450871"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983437","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-02-05DOI: 10.1080/19490976.2025.2455506
Andrea Fumagalli, Anna Castells-Nobau, Dakshat Trivedi, Josep Garre-Olmo, Josep Puig, Rafel Ramos, Lluís Ramió-Torrentà, Vicente Pérez-Brocal, Andrés Moya, Jonathan Swann, Elena Martin-Garcia, Rafael Maldonado, José Manuel Fernández-Real, Jordi Mayneris-Perxachs
{"title":"Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolism.","authors":"Andrea Fumagalli, Anna Castells-Nobau, Dakshat Trivedi, Josep Garre-Olmo, Josep Puig, Rafel Ramos, Lluís Ramió-Torrentà, Vicente Pérez-Brocal, Andrés Moya, Jonathan Swann, Elena Martin-Garcia, Rafael Maldonado, José Manuel Fernández-Real, Jordi Mayneris-Perxachs","doi":"10.1080/19490976.2025.2455506","DOIUrl":"10.1080/19490976.2025.2455506","url":null,"abstract":"<p><p>The relationship between bacteria, cognitive function and obesity is well established, yet the role of archaeal species remains underexplored. We used shotgun metagenomics and neuropsychological tests to identify microbial species associated with cognition in a discovery cohort (IRONMET, <i>n</i> = 125). Interestingly, methanogen archaeas exhibited the strongest positive associations with cognition, particularly <i>Methanobrevibacter smithii</i> (<i>M. smithii</i>). Stratifying individuals by median-centered log ratios (CLR) of <i>M. smithii</i> (low and high <i>M. smithii</i> groups: LMs and HMs) revealed that HMs exhibited better cognition and distinct gut bacterial profiles (PERMANOVA <i>p</i> = 0.001), characterized by increased levels of Verrucomicrobia, Synergistetes and Lentisphaerae species and reduced levels of Bacteroidetes and Proteobacteria. Several of these species were linked to the cognitive test scores. These findings were replicated in a large-scale validation cohort (Aging Imageomics, <i>n</i> = 942). Functional analyses revealed an enrichment of energy, butyrate, and bile acid metabolism in HMs in both cohorts. Global plasma metabolomics by CIL LC-MS in IRONMET identified an enrichment of methylhistidine, phenylacetate, alpha-linolenic and linoleic acid, and secondary bile acid metabolism associated with increased levels of 3-methylhistidine, phenylacetylgluamine, adrenic acid, and isolithocholic acid in the HMs group. Phenylacetate and linoleic acid metabolism also emerged in the Aging Imageomics cohort performing untargeted HPLC-ESI-MS/MS metabolic profiling, while a targeted bile acid profiling identified again isolithocholic acid as one of the most significant bile acid increased in the HMs. 3-Methylhistidine levels were also associated with intense physical activity in a second validation cohort (IRONMET-CGM, <i>n</i> = 116). Finally, FMT from HMs donors improved cognitive flexibility, reduced weight, and altered SCFAs, histidine-, linoleic acid- and phenylalanine-related metabolites in the dorsal striatum of recipient mice. <i>M. smithii</i> seems to interact with the bacterial ecosystem affecting butyrate, histidine, phenylalanine, and linoleic acid metabolism with a positive impact on cognition, constituting a promising therapeutic target to enhance cognitive performance, especially in subjects with obesity.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2455506"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255514","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":"M28 family peptidase derived from <i>Peribacillus frigoritolerans</i> initiates trained immunity to prevent MRSA via the complosome-phosphatidylcholine axis.","authors":"Cheng-Kai Zhou, Zhen-Zhen Liu, Zi-Ran Peng, Xue-Yue Luo, Xiao-Mei Zhang, Jian-Gang Zhang, Liang Zhang, Wei Chen, Yong-Jun Yang","doi":"10.1080/19490976.2025.2484386","DOIUrl":"10.1080/19490976.2025.2484386","url":null,"abstract":"<p><p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) represents a major global health threat due to its resistance to conventional antibiotics. The commensal microbiota maintains a symbiotic relationship with the host, playing essential roles in metabolism, energy regulation, immune modulation, and pathogen control. Mammals harbor a wide range of commensal bacteria capable of producing unique metabolites with potential therapeutic properties. This study demonstrated that M28 family peptidase (M28), derived from commensal bacteria <i>Peribacillus frigoritolerans</i> (<i>P. f</i>), provided protective effects against MRSA-induced pneumonia. M28 enhanced the phagocytosis and bactericidal activity of macrophages by inducing trained immunity. RNA sequencing and metabolomic analyses identified the CFB-C3a-C3aR-HIF-1α axis-mediated phosphatidylcholine accumulation as the key mechanism for M28-induced trained immunity. Phosphatidylcholine, like M28, also induced trained immunity. To enhance M28-mediated therapeutic potential, it was encapsulated in liposomes (M28-LNPs), which exhibited superior immune-stimulating properties compared to M28 alone. In vivo experiments revealed that M28-LNPs significantly reduced bacterial loads and lung damage following MRSA infection, which also provided enhanced protection against <i>Klebsiella pneumoniae</i> and <i>Candida albicans</i>. We first confirmed a link between complement activation and trained immunity, offering valuable insights into the treatment and prevention of complement-related autoimmune diseases.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2484386"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752384","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-04-06DOI: 10.1080/19490976.2025.2483780
Boobalan Thulasinathan, Kanve N Suvilesh, Sumanas Maram, Erik Grossmann, Yezaz Ghouri, Emma Pernas Teixeiro, Joshua Chan, Jussuf T Kaif, Satyanarayana Rachagani
{"title":"The impact of gut microbial short-chain fatty acids on colorectal cancer development and prevention.","authors":"Boobalan Thulasinathan, Kanve N Suvilesh, Sumanas Maram, Erik Grossmann, Yezaz Ghouri, Emma Pernas Teixeiro, Joshua Chan, Jussuf T Kaif, Satyanarayana Rachagani","doi":"10.1080/19490976.2025.2483780","DOIUrl":"10.1080/19490976.2025.2483780","url":null,"abstract":"<p><p>Cancer is a long-term illness that involves an imbalance in cellular and immune functions. It can be caused by a range of factors, including exposure to environmental carcinogens, poor diet, infections, and genetic alterations. Maintaining a healthy gut microbiome is crucial for overall health, and short-chain fatty acids (SCFAs) produced by gut microbiota play a vital role in this process. Recent research has established that alterations in the gut microbiome led to decreased production of SCFA's in lumen of the colon, which associated with changes in the intestinal epithelial barrier function, and immunity, are closely linked to colorectal cancer (CRC) development and its progression. SCFAs influence cancer progression by modifying epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA functions thereby affecting tumor initiation and metastasis. This suggests that restoring SCFA levels in colon through microbiota modulation could serve as an innovative strategy for CRC prevention and treatment. This review highlights the critical relationship between gut microbiota and CRC, emphasizing the potential of targeting SCFAs to enhance gut health and reduce CRC risk.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2483780"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795248","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":"Chikungunya virus drives gut microbiota shifts and IFN-Mediated intestinal repair: insights into microbiota-immune interplay.","authors":"Hongyu Chen, Kaiyun Ding, Cong Tang, Jingwen Xu, Fengyuan Zhang, Yao Yan, Bai Li, Yanan Zhou, Yun Yang, Hao Yang, Qing Huang, Wenhai Yu, Haixuan Wang, Daoju Wu, Shuaiyao Lu, Hongqi Liu","doi":"10.1080/19490976.2025.2512900","DOIUrl":"10.1080/19490976.2025.2512900","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) infection causes joint damage and gastrointestinal clinical symptoms, including vomiting and diarrhea, particularly in elderly populations, reflecting the potential role of gut immunity in infection. However, the mechanisms by which CHIKV induces gastrointestinal diseases remain largely unexplored. This study investigated the characteristics of fecal and gut microbiota, gut metabolites, and gut immunity post-infection using multi-omics analysis. The role of gut microbiota was further validated through Oral antibiotic depletion (Abx). Importantly, a systematic comparison of age-dependent differences in gut microbiota composition and immune responses following CHIKV infection was conducted to elucidate the involvement of gut microbiota in CHIKV pathogenesis. CHIKV joint inoculation induces gastrointestinal infection and histological damage, drives fluctuations in gut microbiota, markedly increasing the abundance of <i>Bacteroides fragilis</i> and <i>Prevotella sp</i>. and upregulates conjugates of taurine and bile acids. CHIKV infection further exacerbates systemic inflammatory burden and activates intestinal interferon (IFN) signaling cascades, which supports gut repair and mucosal regeneration, but low antiviral responses to CHIKV infection compared with that of adult animals. Our results suggest that the gastrointestinal tract, along with its microbes and metabolites, modulates CHIKV infection in an age-dependent manner, providing critical insights for diagnosis, treatment, and novel therapeutic development.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2512900"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225313","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-04-01DOI: 10.1080/19490976.2025.2486519
Mingyao Huang, Quansong Ji, Huiyan Huang, Xiaoqian Wang, Lin Wang
{"title":"Gut microbiota in hepatocellular carcinoma immunotherapy: immune microenvironment remodeling and gut microbiota modification.","authors":"Mingyao Huang, Quansong Ji, Huiyan Huang, Xiaoqian Wang, Lin Wang","doi":"10.1080/19490976.2025.2486519","DOIUrl":"10.1080/19490976.2025.2486519","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with limited treatment options at advanced stages. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, plays a pivotal role in regulating immune responses through the gut-liver axis. Emerging evidence underscores its impact on HCC progression and the efficacy of immunotherapy. This review explores the intricate interactions between gut microbiota and the immune system in HCC, with a focus on key immune cells and pathways involved in tumor immunity. Additionally, it highlights strategies for modulating the gut microbiota - such as fecal microbiota transplantation, dietary interventions, and probiotics - as potential approaches to enhancing immunotherapy outcomes. A deeper understanding of these mechanisms could pave the way for novel therapeutic strategies aimed at improving patient prognosis.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2486519"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752382","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-06-11DOI: 10.1080/19490976.2025.2516703
Yan Hui, Dennis Sandris Nielsen, Lukasz Krych
{"title":"<i>De novo</i> clustering of long-read amplicons improves phylogenetic insight into microbiome data.","authors":"Yan Hui, Dennis Sandris Nielsen, Lukasz Krych","doi":"10.1080/19490976.2025.2516703","DOIUrl":"10.1080/19490976.2025.2516703","url":null,"abstract":"<p><p>Long-read amplicon profiling through read classification limits phylogenetic analysis of amplicons while community analysis of multicopy genes, relying on unique molecular identifier (UMI) corrections, often demands deep sequencing. To address this, we present a long amplicon consensus analysis (LACA) workflow employing multiple <i>de novo</i> clustering approaches based on sequence dissimilarity. LACA controls the average error rate of corrected sequences below 1% for the Oxford Nanopore Technologies (ONT) R9.4.1 and ONT R10.3 data, 0.2% for ONT R10.4.1, and 0.1% for high-accuracy ONT Duplex and Pacific Biosciences (PacBio) circular consensus sequencing (CCS) data in both simulated 16S rRNA and real 16-23S rRNA amplicon datasets. In high-accuracy PacBio CCS data, the clustering-based correction matched UMI correction, while outperforming 4× UMI correction in noisy ONT R10.3 and R9.4.1 data. Notably, LACA preserved phylogenetic fidelity in long operational taxonomic units and enhanced microbiome-wide phenotype characterization for synthetic mock communities and human vaginal samples.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2516703"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266130","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-03-11DOI: 10.1080/19490976.2025.2474141
Bryson W Katona, Ashutosh Shukla, Weiming Hu, Thomas Nyul, Christina Dudzik, Alex Arvanitis, Daniel Clay, Michaela Dungan, Marina Weber, Vincent Tu, Fuhua Hao, Shuheng Gan, Lillian Chau, Anna M Buchner, Gary W Falk, David L Jaffe, Gregory Ginsberg, Suzette N Palmer, Xiaowei Zhan, Andrew D Patterson, Kyle Bittinger, Josephine Ni
{"title":"Microbiota and metabolite-based prediction tool for colonic polyposis with and without a known genetic driver.","authors":"Bryson W Katona, Ashutosh Shukla, Weiming Hu, Thomas Nyul, Christina Dudzik, Alex Arvanitis, Daniel Clay, Michaela Dungan, Marina Weber, Vincent Tu, Fuhua Hao, Shuheng Gan, Lillian Chau, Anna M Buchner, Gary W Falk, David L Jaffe, Gregory Ginsberg, Suzette N Palmer, Xiaowei Zhan, Andrew D Patterson, Kyle Bittinger, Josephine Ni","doi":"10.1080/19490976.2025.2474141","DOIUrl":"10.1080/19490976.2025.2474141","url":null,"abstract":"<p><p>Despite extensive investigations into the microbiome and metabolome changes associated with colon polyps and colorectal cancer (CRC), the microbiome and metabolome profiles of individuals with colonic polyposis, including those with (Gene-pos) and without (Gene-neg) a known genetic driver, remain comparatively unexplored. Using colon biopsies, polyps, and stool from patients with Gene-pos adenomatous polyposis (<i>N</i> = 9), Gene-neg adenomatous polyposis (<i>N</i> = 18), and serrated polyposis syndrome (SPS, <i>N</i> = 11), we demonstrated through 16S rRNA sequencing that the mucosa-associated microbiota in individuals with colonic polyposis is representative of the microbiota associated with small polyps, and that both Gene-pos and SPS cohorts exhibit differential microbiota populations relative to Gene-neg polyposis cohorts. Furthermore, we used these differential microbiota taxa to perform linear discriminant analysis to differentiate Gene-neg subjects from Gene-pos and from SPS subjects with an accuracy of 89% and 93% respectively. Stool metabolites were quantified via <sup>1</sup>H NMR, revealing an increase in alanine in SPS subjects relative to non-polyposis subjects, and Partial Least Squares Discriminant Analysis (PLS-DA) analysis indicated that the proportion of leucine to tyrosine in fecal samples may be predictive of SPS. Use of these microbial and metabolomic signatures may allow for better diagnostric and risk-stratification tools for colonic polyposis patients and their families as well as promote development of microbiome-targeted approaches for polyp prevention.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2474141"},"PeriodicalIF":11.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604543","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2025-04-07DOI: 10.1080/19490976.2025.2477819
Fatima A Aboulalazm, Alexis B Kazen, Orlando deLeon, Susanne Müller, Fatima L Saravia, Valery Lozada-Fernandez, Matthew A Hadiono, Robert F Keyes, Brian C Smith, Stephanie L Kellogg, Justin L Grobe, Tammy L Kindel, John R Kirby
{"title":"Reutericyclin, a specialized metabolite of <i>Limosilactobacillus reuteri</i>, mitigates risperidone-induced weight gain in mice.","authors":"Fatima A Aboulalazm, Alexis B Kazen, Orlando deLeon, Susanne Müller, Fatima L Saravia, Valery Lozada-Fernandez, Matthew A Hadiono, Robert F Keyes, Brian C Smith, Stephanie L Kellogg, Justin L Grobe, Tammy L Kindel, John R Kirby","doi":"10.1080/19490976.2025.2477819","DOIUrl":"10.1080/19490976.2025.2477819","url":null,"abstract":"<p><p>The role of xenobiotic disruption of microbiota, corresponding dysbiosis, and potential links to host metabolic diseases are of critical importance. In this study, we used a widely prescribed antipsychotic drug, risperidone, known to influence weight gain in humans, to induce weight gain in C57BL/6J female mice. We hypothesized that microbes essential for maintaining gut homeostasis and energy balance would be depleted following treatment with risperidone, leading to enhanced weight gain relative to controls. Thus, we performed metagenomic analyses on stool samples to identify microbes that were excluded in risperidone-treated animals but remained present in controls. We identified multiple taxa including <i>Limosilactobacillus reuteri</i> as a candidate for further study. Oral supplementation with <i>L. reuteri</i> protected against risperidone-induced weight gain (RIWG) and was dependent on cellular production of a specialized metabolite, reutericyclin. Further, synthetic reutericyclin was sufficient to mitigate RIWG. Both synthetic reutericyclin and <i>L. reuteri</i> restored energy balance in the presence of risperidone to mitigate excess weight gain and induce shifts in the microbiome associated with leanness. In total, our results identify reutericyclin production by <i>L. reuteri</i> as a potential probiotic to restore energy balance induced by risperidone and to promote leanness.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2477819"},"PeriodicalIF":11.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795245","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}
Gut MicrobesPub Date : 2025-12-01Epub Date: 2024-12-23DOI: 10.1080/19490976.2024.2439105
Matthieu Minty, Alberic Germain, Jiuwen Sun, Gracia Kaglan, Florence Servant, Benjamin Lelouvier, Emiri Misselis, Radu Mircea Neagoe, Menghini Rossella, Marina Cardellini, Rémy Burcelin, Massimo Federici, José Manuel Fernandez-Real, Vincent Blasco-Baque
{"title":"Identifying the location-dependent adipose tissue bacterial DNA signatures in obese patients that predict body weight loss.","authors":"Matthieu Minty, Alberic Germain, Jiuwen Sun, Gracia Kaglan, Florence Servant, Benjamin Lelouvier, Emiri Misselis, Radu Mircea Neagoe, Menghini Rossella, Marina Cardellini, Rémy Burcelin, Massimo Federici, José Manuel Fernandez-Real, Vincent Blasco-Baque","doi":"10.1080/19490976.2024.2439105","DOIUrl":"https://doi.org/10.1080/19490976.2024.2439105","url":null,"abstract":"<p><p>Recent sets of evidence have described profiles of 16S rDNA sequences in host tissues, notably in fat pads that are significantly overrepresented and can serve as signatures of metabolic disease. However, these recent and original observations need to be further detailed and functionally defined. Here, using state-of-the-art targeted DNA sequencing and discriminant predictive approaches, we describe, from the longitudinal FLORINASH cohort of patients who underwent bariatric surgery, visceral, and subcutaneous fat pad-specific bacterial 16SrRNA signatures. The corresponding <i>Porphyromonadaceae</i>, <i>Campylobacteraceae</i>, <i>Prevotellaceae</i>, <i>Actimomycetaceae</i>, <i>Veillonellaceae</i>, <i>Anaerivoracaceae</i>, <i>Fusobacteriaceae</i>, and the <i>Clostridium family XI</i> 16SrRNA DNA segment profiles are signatures of the subcutaneous adipose depot while <i>Pseudomonadaceae</i> and <i>Micrococcacecae</i>, 16SrRNA DNA sequence profiles characterize the visceral adipose depot. In addition, we have further identified that a specific pre-bariatric surgery adipose tissue bacterial DNA signature predicts the efficacy of body weight loss in obese patients 5-10 years after the surgery. 16SrRNA signatures discriminate (ROC ~ 1) the patients who did not maintain bodyweight loss and those who did. Second, from the 16SrRNA sequences we infer potential pathways suggestive of catabolic biochemical activities that could be signatures of subcutaneous adipose depots that predict body weight loss.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2439105"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876909","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}