Evidence suggests that socioeconomic position (SEP) may shape the gut microbiota (GM), representing a mechanism through which social and environmental factors may drive health inequalities, yet no systematic review has examined this association. In this narrative systematic review, we searched PubMed, Web of Science, and Scopus up to 30 November 2024 for observational studies examining associations between measures of SEP and GM diversity, composition, or function in participants of any age, ethnicity, or location. We identified 1,479 unique studies, of which 26 met the inclusion criteria for this review. Associations were observed between SEP indicators and GM features, including alpha (α) and beta (β) diversity, taxonomic composition, and functional pathways. Notably, socioeconomic patterns in α-diversity differed by context, with greater diversity observed in advantaged groups in high-income countries (HICs) but in disadvantaged groups in low- and middle-income countries (LMICs). Differences in β-diversity suggest that advantaged and disadvantaged groups have distinct GM profiles. Furthermore, considerable heterogeneity was evident across studies, particularly in sampling, sequencing, and analytical methods. Overall, socioeconomic-related differences in the GM are evident globally, highlighting the microbiota as a potential target for interventions aimed at reducing health disparities. Further research employing larger and more diverse cohorts, longitudinal designs, metagenomic sequencing approaches, and comprehensive measurement and adjustment of key covariates is needed to deepen understanding of this relationship.
有证据表明，社会经济地位（SEP）可能会影响肠道微生物群（GM），这是社会和环境因素可能导致健康不平等的一种机制，但尚未有系统的综述研究这种关联。在这篇叙叙性系统综述中，我们检索了PubMed、Web of Science和Scopus，检索了截至2024年11月30日的观察性研究，研究了任何年龄、种族或地点的参与者中SEP和转基因多样性、组成或功能之间的关系。我们确定了1479项独特的研究，其中26项符合本综述的纳入标准。SEP指标与转基因特征(α （α)和β (β)多样性、分类组成和功能通路）之间存在相关性。值得注意的是，α-多样性的社会经济模式因环境而异，在高收入国家（HICs）的优势群体中观察到更大的多样性，而在低收入和中等收入国家（LMICs）的弱势群体中观察到更大的多样性。β多样性的差异表明，优势群体和弱势群体具有不同的转基因概况。此外，相当大的异质性在研究中是明显的，特别是在采样，测序和分析方法。总体而言，基因改造中与社会经济相关的差异在全球范围内是明显的，这突出表明微生物群是旨在减少健康差距的干预措施的潜在目标。进一步的研究需要采用更大、更多样化的队列、纵向设计、宏基因组测序方法以及对关键协变量的综合测量和调整来加深对这种关系的理解。
{"title":"Socioeconomic position and the gut microbiota: a narrative synthesis of the association and recommendations.","authors":"Jasmine Samantha Ratcliff,Meena Kumari,Patrick Varga-Weisz,Rick O'Gorman","doi":"10.1080/19490976.2026.2623356","DOIUrl":"https://doi.org/10.1080/19490976.2026.2623356","url":null,"abstract":"Evidence suggests that socioeconomic position (SEP) may shape the gut microbiota (GM), representing a mechanism through which social and environmental factors may drive health inequalities, yet no systematic review has examined this association. In this narrative systematic review, we searched PubMed, Web of Science, and Scopus up to 30 November 2024 for observational studies examining associations between measures of SEP and GM diversity, composition, or function in participants of any age, ethnicity, or location. We identified 1,479 unique studies, of which 26 met the inclusion criteria for this review. Associations were observed between SEP indicators and GM features, including alpha (α) and beta (β) diversity, taxonomic composition, and functional pathways. Notably, socioeconomic patterns in α-diversity differed by context, with greater diversity observed in advantaged groups in high-income countries (HICs) but in disadvantaged groups in low- and middle-income countries (LMICs). Differences in β-diversity suggest that advantaged and disadvantaged groups have distinct GM profiles. Furthermore, considerable heterogeneity was evident across studies, particularly in sampling, sequencing, and analytical methods. Overall, socioeconomic-related differences in the GM are evident globally, highlighting the microbiota as a potential target for interventions aimed at reducing health disparities. Further research employing larger and more diverse cohorts, longitudinal designs, metagenomic sequencing approaches, and comprehensive measurement and adjustment of key covariates is needed to deepen understanding of this relationship.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"84 1","pages":"2623356"},"PeriodicalIF":12.2,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095514","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}
The human gut microbiome is a cornerstone of health, yet conventional probiotic therapies often exhibit limited efficacy owing to heterogeneity in host-microbe-environment dynamics. This review dissects the biological and environmental drivers of such variability and highlights emerging frameworks that integrate cross-sectional and longitudinal multi-omics data to predict probiotic treatment outcomes and host metabolic responses. We further spotlight breakthroughs in methodological development in efficient mining and engineering of probiotic strains, which enable the rational design of functionally enhanced, personalized probiotics. By synthesizing these advances, the review underscores the transformative potential of combining data-driven models with precision-engineered microbial therapeutics to address current limitations and usher in a new era of future microbiome-informed nutrition and personalized interventions.
{"title":"Precise probiotic therapy: Advances, bottlenecks, and the road to microbiome-informed nutrition.","authors":"Yuesong Jiang,Shuaiming Jiang,Zhengting Wang,Pengfei Zhu,Jiachao Zhang,Fei Teng,Shi Huang","doi":"10.1080/19490976.2026.2623359","DOIUrl":"https://doi.org/10.1080/19490976.2026.2623359","url":null,"abstract":"The human gut microbiome is a cornerstone of health, yet conventional probiotic therapies often exhibit limited efficacy owing to heterogeneity in host-microbe-environment dynamics. This review dissects the biological and environmental drivers of such variability and highlights emerging frameworks that integrate cross-sectional and longitudinal multi-omics data to predict probiotic treatment outcomes and host metabolic responses. We further spotlight breakthroughs in methodological development in efficient mining and engineering of probiotic strains, which enable the rational design of functionally enhanced, personalized probiotics. By synthesizing these advances, the review underscores the transformative potential of combining data-driven models with precision-engineered microbial therapeutics to address current limitations and usher in a new era of future microbiome-informed nutrition and personalized interventions.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"1 1","pages":"2623359"},"PeriodicalIF":12.2,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089075","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}
Glioblastoma (GBM) is the most common and malignant brain tumor in adult humans. Recent studies have demonstrated a link between the composition of the gut microbiota and glioma progression. Here, we describe that the growth of glioma in mice is inversely correlated with the relative abundance of the anaerobic bacterium Muribaculum intestinale in the feces. We found that M. intestinale administration: 1) induced an inflammatory environment in the gut; 2) reduced glioma growth; 3) increased the pro-inflammatory profile of tumor-associated microglial cells and the frequency of CD8+ T cells; and 4) increased the peripheral TNF-α levels. The effects induced by M. intestinale administration were significantly attenuated upon toll-like receptor 2 (TLR2) silencing using TLR2-targeting siRNA. As a pattern-recognition receptor, TLR2 detects microbial-associated molecular patterns and orchestrates host immune responses to infection. Collectively, these data demonstrate that M. intestinale induces a pro-inflammatory response in glioma bearing mice, inhibiting tumor growth via TLR2-dependent signaling.
{"title":"Muribaculum intestinale negatively impacts glioma growth in mice through the toll-like receptor 2.","authors":"Francesco Marrocco,Germana Cocozza,Fabrizio Antonangeli,Rizwan Khan,Giuseppe Pietropaolo,Abdechakour Elkihel,Gabriele Favaretto,Xingzi Lin,Romina Mancinelli,Ludovica Maria Busdraghi,Alice Reccagni,Gianluca Scarno,Giuseppe Sciumè,Mattia Laffranchi,Ling Peng,Valerio Iebba,Silvano Sozzani,Giuseppina D'Alessandro,Cristina Limatola","doi":"10.1080/19490976.2026.2623349","DOIUrl":"https://doi.org/10.1080/19490976.2026.2623349","url":null,"abstract":"Glioblastoma (GBM) is the most common and malignant brain tumor in adult humans. Recent studies have demonstrated a link between the composition of the gut microbiota and glioma progression. Here, we describe that the growth of glioma in mice is inversely correlated with the relative abundance of the anaerobic bacterium Muribaculum intestinale in the feces. We found that M. intestinale administration: 1) induced an inflammatory environment in the gut; 2) reduced glioma growth; 3) increased the pro-inflammatory profile of tumor-associated microglial cells and the frequency of CD8+ T cells; and 4) increased the peripheral TNF-α levels. The effects induced by M. intestinale administration were significantly attenuated upon toll-like receptor 2 (TLR2) silencing using TLR2-targeting siRNA. As a pattern-recognition receptor, TLR2 detects microbial-associated molecular patterns and orchestrates host immune responses to infection. Collectively, these data demonstrate that M. intestinale induces a pro-inflammatory response in glioma bearing mice, inhibiting tumor growth via TLR2-dependent signaling.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"8 1","pages":"2623349"},"PeriodicalIF":12.2,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073215","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}
Colostrum secretory immunoglobulin A (sIgA) confers the first immune defense line for neonates to adapt to the external environment, while gut microbes have received attention for their high reactivity with sIgA. Here, we report that high levels of sIgA in sow colostrum are associated with the enrichment of Akkermansia muciniphila and branched-chain amino acid (BCAA) metabolism in the intestine. Mechanistically, we demonstrate through mice models that A. muciniphila-derived nifJ mediates BCAA degradation to branched short-chain fatty acids, which further enhance transforming growth factor-β (TGF-β) and C-C motif chemokine ligand 28 (CCL28) expression in mammary tissues through the G protein-coupled receptor pathway, ultimately increasing sIgA content in colostrum. These findings establish a mechanistic link between the maternal gut microbiota and offspring immune development, highlighting the specific functional localization of the nifJ gene of A. muciniphila.
{"title":"Akkermansia muciniphila's nifJ gene enhances colostrum sIgA synthesis by branched-chain amino acid degradation to branched short-chain fatty acids.","authors":"Deyuan Wu,Fuyong Li,Wenyu Xiong,Zihao Huang,Kaidi Ma,Jun Huang,Sensen Cai,Jinping Deng,Jie Peng,Xiong Xia,Chengquan Tan","doi":"10.1080/19490976.2026.2620128","DOIUrl":"https://doi.org/10.1080/19490976.2026.2620128","url":null,"abstract":"Colostrum secretory immunoglobulin A (sIgA) confers the first immune defense line for neonates to adapt to the external environment, while gut microbes have received attention for their high reactivity with sIgA. Here, we report that high levels of sIgA in sow colostrum are associated with the enrichment of Akkermansia muciniphila and branched-chain amino acid (BCAA) metabolism in the intestine. Mechanistically, we demonstrate through mice models that A. muciniphila-derived nifJ mediates BCAA degradation to branched short-chain fatty acids, which further enhance transforming growth factor-β (TGF-β) and C-C motif chemokine ligand 28 (CCL28) expression in mammary tissues through the G protein-coupled receptor pathway, ultimately increasing sIgA content in colostrum. These findings establish a mechanistic link between the maternal gut microbiota and offspring immune development, highlighting the specific functional localization of the nifJ gene of A. muciniphila.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"1 1","pages":"2620128"},"PeriodicalIF":12.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073047","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}
Gut microbiota dysbiosis has been implicated in the pathogenesis of irritable bowel syndrome (IBS), a globally prevalent functional gastrointestinal disorder; however, mechanistic insights remain limited. We determined that the bacterium Fusobacterium nucleatum (F. nucleatum) played a pathogenic role in a murine model of IBS. Monocolonization of antibiotic-treated or germ-free mice with F. nucleatum induced IBS-like symptoms, including visceral hypersensitivity, increased fecal water content, and accelerated gastrointestinal transit, accompanied by mast cell activation. These effects were effectively prevented by treatment with the antibiotic metronidazole, as well as by the mast cell depleting agent imatinib or the mast cell stabilizer sodium cromoglicate. Mechanistically, F. nucleatum upregulated the expression of purine nucleoside phosphorylase (PNP) in intestinal epithelial cells (IECs), a key enzyme in the purine degradation pathway. The elevated PNP activity promoted purine degradation and uric acid production in IECs, which in turn directly activated mast cells. This F. nucleatum-driven mast cell activation mediated IBS-like symptoms in ABX treated mice but was abrogated by blocking uric acid synthesis. In summary, our findings highlight the crucial role of purine metabolism reprogramming and low-grade mucosal immune responses in F. nucleatum-mediated IBS-like symptoms in mice, providing promising therapeutic perspectives for targeting F. nucleatum-positive IBS patients.
{"title":"Fusobacterium nucleatum plays a pathogenic role in a murine model of irritable bowel syndrome by modulating intestinal purine metabolism and promoting mast cell activation.","authors":"Songyuan Hou,Tingting Ning,Si Liu,Xinyi Yang,Haozhen Ye,Yesheng Zhou,Chenxu Wang,Jiaqi Zhu,Shaochong Lu,Nan Zhang,Shengtao Zhu","doi":"10.1080/19490976.2026.2620124","DOIUrl":"https://doi.org/10.1080/19490976.2026.2620124","url":null,"abstract":"Gut microbiota dysbiosis has been implicated in the pathogenesis of irritable bowel syndrome (IBS), a globally prevalent functional gastrointestinal disorder; however, mechanistic insights remain limited. We determined that the bacterium Fusobacterium nucleatum (F. nucleatum) played a pathogenic role in a murine model of IBS. Monocolonization of antibiotic-treated or germ-free mice with F. nucleatum induced IBS-like symptoms, including visceral hypersensitivity, increased fecal water content, and accelerated gastrointestinal transit, accompanied by mast cell activation. These effects were effectively prevented by treatment with the antibiotic metronidazole, as well as by the mast cell depleting agent imatinib or the mast cell stabilizer sodium cromoglicate. Mechanistically, F. nucleatum upregulated the expression of purine nucleoside phosphorylase (PNP) in intestinal epithelial cells (IECs), a key enzyme in the purine degradation pathway. The elevated PNP activity promoted purine degradation and uric acid production in IECs, which in turn directly activated mast cells. This F. nucleatum-driven mast cell activation mediated IBS-like symptoms in ABX treated mice but was abrogated by blocking uric acid synthesis. In summary, our findings highlight the crucial role of purine metabolism reprogramming and low-grade mucosal immune responses in F. nucleatum-mediated IBS-like symptoms in mice, providing promising therapeutic perspectives for targeting F. nucleatum-positive IBS patients.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"71 1","pages":"2620124"},"PeriodicalIF":12.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069978","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}
Pub Date : 2026-01-28DOI: 10.1080/19490976.2026.2615490
Selvin Solis,Elaina M Maldonado,Subhankar Mukhopadhyay,Gwénaël Jan,José María Landete,Carlos Maluquer de Motes,Jorge Gutierrez-Merino
The gut microbiome plays a critical role in health, disease and immunity. To date, we have access to large datasets describing how the microbial diversity present in the gut correlates with many clinical conditions. However, the microbiome composition is taxonomically complex; influenced by many environmental factors; and variable between individuals and communities, thereby limiting functional and mechanistic insights into the microbiota‒host interactions. We are still unsure of the molecular mechanisms by which gut commensal microbes intrinsically possess to interact with the immune system and induce beneficial responses. This study has addressed this important question by revealing that only certain members of Lactobacillaceae, a bacterial family very well known for its probiotic properties, interact very intimately with macrophages because of their ability to simultaneously overexpress adhesive cell wall proteins and to self-aggregate, leading to significant production of type I interferon (IFN-I) cytokines. IFN-I cytokines are essential to confer protection against viral infections and auto-immune disorders. Specifically, we have proved that this enhanced IFN-I feature is strain-dependent and predominantly driven by cGAS, a molecule that activates the cytosolic sensor STING upon the recognition of bacterial DNA. Furthermore, another cytosolic sensor, NOD2, seems to be an additional stimulus to amplify IFN-I production, suggesting the involvement of successive molecular events for a prominent probiotic response. Our findings provide insight into how specific molecules of probiotic bacteria modulate or stimulate host responses, providing a better understanding of the molecular crosstalk between the microbiome and immune cells.
{"title":"Self-aggregating Lactiplantibacillus plantarum enhances type-I interferon responses via the cytosolic sensors NOD2 and cGAS.","authors":"Selvin Solis,Elaina M Maldonado,Subhankar Mukhopadhyay,Gwénaël Jan,José María Landete,Carlos Maluquer de Motes,Jorge Gutierrez-Merino","doi":"10.1080/19490976.2026.2615490","DOIUrl":"https://doi.org/10.1080/19490976.2026.2615490","url":null,"abstract":"The gut microbiome plays a critical role in health, disease and immunity. To date, we have access to large datasets describing how the microbial diversity present in the gut correlates with many clinical conditions. However, the microbiome composition is taxonomically complex; influenced by many environmental factors; and variable between individuals and communities, thereby limiting functional and mechanistic insights into the microbiota‒host interactions. We are still unsure of the molecular mechanisms by which gut commensal microbes intrinsically possess to interact with the immune system and induce beneficial responses. This study has addressed this important question by revealing that only certain members of Lactobacillaceae, a bacterial family very well known for its probiotic properties, interact very intimately with macrophages because of their ability to simultaneously overexpress adhesive cell wall proteins and to self-aggregate, leading to significant production of type I interferon (IFN-I) cytokines. IFN-I cytokines are essential to confer protection against viral infections and auto-immune disorders. Specifically, we have proved that this enhanced IFN-I feature is strain-dependent and predominantly driven by cGAS, a molecule that activates the cytosolic sensor STING upon the recognition of bacterial DNA. Furthermore, another cytosolic sensor, NOD2, seems to be an additional stimulus to amplify IFN-I production, suggesting the involvement of successive molecular events for a prominent probiotic response. Our findings provide insight into how specific molecules of probiotic bacteria modulate or stimulate host responses, providing a better understanding of the molecular crosstalk between the microbiome and immune cells.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"143 1","pages":"2615490"},"PeriodicalIF":12.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069963","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}
Pub Date : 2026-01-27DOI: 10.1080/19490976.2026.2616066
Tyrus J Perdue,Cassandra E Newkirk,Robert Beblavy,Antti E Seppo,Erin C Davis,Michael B Sohn,Kirsi M Järvinen,Cynthia L Monaco
Atopic disease prevalence, including atopic dermatitis, food allergy, asthma, and allergic rhinitis, has risen dramatically in industrialized countries. Traditional, single family farming lifestyles protect against atopic disease, but the mechanisms are incompletely understood. While there are established epidemiologic connections between childhood respiratory viral infections and the infant gut bacterial microbiome with allergic disease development, the influence of the early enteric virome on atopic disease development is unknown. We analyzed the enteric virome in 131 infants from high-atopy-risk urban/suburban environments and low-atopic-risk single-family farming communities. While similar at 12 months, enteric bacteriophage communities significantly differed by farm-life versus urban lifestyle at six weeks and six months of age. A lifestyle protective from atopic disease demonstrated higher colonization rates of Bifidobacterium longum subsp. infantis (B. infantis), an important beneficial commensal, with phageome communities differing in infants colonized by B. infantis at all time points. Simultaneously, Mastadenovirus and Bocaparvovirus were more prevalent in urban infant stools at six months of age. Sparser phage-phage networks were found at all timepoints in infants who later developed atopic disease. These data suggest that the early infant enteric DNA virome develops differently in farming and urban lifestyles and may factor into risk of atopic disease development.
{"title":"The enteric DNA virome differs in infants at risk for atopic disease.","authors":"Tyrus J Perdue,Cassandra E Newkirk,Robert Beblavy,Antti E Seppo,Erin C Davis,Michael B Sohn,Kirsi M Järvinen,Cynthia L Monaco","doi":"10.1080/19490976.2026.2616066","DOIUrl":"https://doi.org/10.1080/19490976.2026.2616066","url":null,"abstract":"Atopic disease prevalence, including atopic dermatitis, food allergy, asthma, and allergic rhinitis, has risen dramatically in industrialized countries. Traditional, single family farming lifestyles protect against atopic disease, but the mechanisms are incompletely understood. While there are established epidemiologic connections between childhood respiratory viral infections and the infant gut bacterial microbiome with allergic disease development, the influence of the early enteric virome on atopic disease development is unknown. We analyzed the enteric virome in 131 infants from high-atopy-risk urban/suburban environments and low-atopic-risk single-family farming communities. While similar at 12 months, enteric bacteriophage communities significantly differed by farm-life versus urban lifestyle at six weeks and six months of age. A lifestyle protective from atopic disease demonstrated higher colonization rates of Bifidobacterium longum subsp. infantis (B. infantis), an important beneficial commensal, with phageome communities differing in infants colonized by B. infantis at all time points. Simultaneously, Mastadenovirus and Bocaparvovirus were more prevalent in urban infant stools at six months of age. Sparser phage-phage networks were found at all timepoints in infants who later developed atopic disease. These data suggest that the early infant enteric DNA virome develops differently in farming and urban lifestyles and may factor into risk of atopic disease development.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"42 1","pages":"2616066"},"PeriodicalIF":12.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056780","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}
Pub Date : 2026-01-26DOI: 10.1080/19490976.2026.2617694
Alex Peh,Evany Dinakis,Michael Nakai,Rikeish R Muralitharan,Samoda Rupasinghe,Jenny L Wilson,Connie H Y Wong,Hamdi A Jama,Charlotte M O Barker,Mahnaz Modarresi,Barbara K Kemp-Harper,Tenghao Zheng,Francine Z Marques,Brad R S Broughton
Systemic infections are a common cause of complications and death after stroke. These infections can occur due to the breakdown of the gut epithelial barrier and the translocation of bacteria from the gut to peripheral systemic tissues. However, it remains unclear whether gut bacteria also translocate to the brain and contribute to stroke-induced neuronal damage. In this study, we observed a significant number of peptidoglycan- and lipopolysaccharide-positive bacteria in the ischemic hemisphere of mice subjected to either photothrombotic (PT) stroke or middle cerebral artery occlusion (MCAO). In contrast, no bacteria were observed in the ischemic brains of germ-free mice following MCAO. Absolute quantification via PCR also revealed increased bacteria in the ischemic hemisphere and blood of PT mice. Bacterial translocation to the brain is associated with the breakdown of the gut-epithelial and blood-brain barriers. Although inhibition of sympathetic tone reduces gut-epithelial barrier permeability, the bacterial load in the brain and functional deficits poststroke, it does not affect cerebral apoptosis, neuroinflammation or infarct volume. Collectively, these findings indicate that activation of the sympathetic nervous system after stroke promotes the migration of gut-derived bacteria into the ischemic brain, and this process worsens motor function in mice.
{"title":"Gut bacteria presence in the brain is increased after ischemic stroke in mice.","authors":"Alex Peh,Evany Dinakis,Michael Nakai,Rikeish R Muralitharan,Samoda Rupasinghe,Jenny L Wilson,Connie H Y Wong,Hamdi A Jama,Charlotte M O Barker,Mahnaz Modarresi,Barbara K Kemp-Harper,Tenghao Zheng,Francine Z Marques,Brad R S Broughton","doi":"10.1080/19490976.2026.2617694","DOIUrl":"https://doi.org/10.1080/19490976.2026.2617694","url":null,"abstract":"Systemic infections are a common cause of complications and death after stroke. These infections can occur due to the breakdown of the gut epithelial barrier and the translocation of bacteria from the gut to peripheral systemic tissues. However, it remains unclear whether gut bacteria also translocate to the brain and contribute to stroke-induced neuronal damage. In this study, we observed a significant number of peptidoglycan- and lipopolysaccharide-positive bacteria in the ischemic hemisphere of mice subjected to either photothrombotic (PT) stroke or middle cerebral artery occlusion (MCAO). In contrast, no bacteria were observed in the ischemic brains of germ-free mice following MCAO. Absolute quantification via PCR also revealed increased bacteria in the ischemic hemisphere and blood of PT mice. Bacterial translocation to the brain is associated with the breakdown of the gut-epithelial and blood-brain barriers. Although inhibition of sympathetic tone reduces gut-epithelial barrier permeability, the bacterial load in the brain and functional deficits poststroke, it does not affect cerebral apoptosis, neuroinflammation or infarct volume. Collectively, these findings indicate that activation of the sympathetic nervous system after stroke promotes the migration of gut-derived bacteria into the ischemic brain, and this process worsens motor function in mice.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"29 1","pages":"2617694"},"PeriodicalIF":12.2,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044598","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}
Pub Date : 2026-01-23DOI: 10.1080/19490976.2026.2620127
Yunfeng Gao,Shima Shahbaz,Shokrollah Elahi,Tanya M Monaghan, ,Dina Kao
Fecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection (rCDI), yet its immunological mechanisms remain poorly defined. While bacterial engraftment and recovery of microbial diversity are central to FMT efficacy, accumulating evidence suggests that host immune reprogramming is involved. In murine models, regulatory CD4⁺ T cells are indispensable for clearing C. difficile. To address this mechanistic gap, we examined systemic immune reprogramming following FMT by performing flow cytometry and single-cell RNA sequencing (scRNA-seq) on a subset of successfully treated participants from a clinical trial comparing lyophilized FMT (LFMT) with lyophilized sterile fecal filtrate (LSFF, no live bacteria) for preventing rCDI. Flow cytometry was performed on peripheral mononuclear cells from 19 LFMT recipients and 18 LSFF recipients, and scRNA-seq analysis was performed on two LFMT recipients. Although flow cytometry results did not show significant changes in the assessed markers after rCDI resolution in either treatment group, exploratory scRNA-seq in the two LFMT recipients revealed distinct LFMT-associated transcriptional signatures across adaptive and innate-like lymphocyte populations. LFMT was associated with upregulated activation and regulatory genes (CD69, STAT1, TOX, RORA, FOXP3) in CD4⁺ and CD8⁺ T cells, suggesting enhanced immune regulation with reduced cytotoxic gene expression (GZMB, PRF1, GNLY). Innate-like lymphocytes displayed broad activation, with natural killer cells showing increased KLRD1, PRF1, and IL2RB and mucosal-associated invariant T cells (MAIT cells) upregulating STAT1, JUN, and RORA while downregulating KLRB1 and STAT3. These transcriptional programs are consistent with recalibration of T cell homeostasis and innate-like lymphocyte activation, potentially driven by microbial restoration. Collectively, this exploratory study provides the first single-cell immune atlas of LFMT in rCDI, identifying coordinated activation of regulatory, effector, and innate immune pathways. Given the small sample size, these findings should be considered hypothesis-generating, requiring validation in larger cohorts.
{"title":"Distinct T and innate-like lymphocyte reprogramming following lyophilized fecal microbiota transplantation in recurrent C. difficile infection.","authors":"Yunfeng Gao,Shima Shahbaz,Shokrollah Elahi,Tanya M Monaghan, ,Dina Kao","doi":"10.1080/19490976.2026.2620127","DOIUrl":"https://doi.org/10.1080/19490976.2026.2620127","url":null,"abstract":"Fecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection (rCDI), yet its immunological mechanisms remain poorly defined. While bacterial engraftment and recovery of microbial diversity are central to FMT efficacy, accumulating evidence suggests that host immune reprogramming is involved. In murine models, regulatory CD4⁺ T cells are indispensable for clearing C. difficile. To address this mechanistic gap, we examined systemic immune reprogramming following FMT by performing flow cytometry and single-cell RNA sequencing (scRNA-seq) on a subset of successfully treated participants from a clinical trial comparing lyophilized FMT (LFMT) with lyophilized sterile fecal filtrate (LSFF, no live bacteria) for preventing rCDI. Flow cytometry was performed on peripheral mononuclear cells from 19 LFMT recipients and 18 LSFF recipients, and scRNA-seq analysis was performed on two LFMT recipients. Although flow cytometry results did not show significant changes in the assessed markers after rCDI resolution in either treatment group, exploratory scRNA-seq in the two LFMT recipients revealed distinct LFMT-associated transcriptional signatures across adaptive and innate-like lymphocyte populations. LFMT was associated with upregulated activation and regulatory genes (CD69, STAT1, TOX, RORA, FOXP3) in CD4⁺ and CD8⁺ T cells, suggesting enhanced immune regulation with reduced cytotoxic gene expression (GZMB, PRF1, GNLY). Innate-like lymphocytes displayed broad activation, with natural killer cells showing increased KLRD1, PRF1, and IL2RB and mucosal-associated invariant T cells (MAIT cells) upregulating STAT1, JUN, and RORA while downregulating KLRB1 and STAT3. These transcriptional programs are consistent with recalibration of T cell homeostasis and innate-like lymphocyte activation, potentially driven by microbial restoration. Collectively, this exploratory study provides the first single-cell immune atlas of LFMT in rCDI, identifying coordinated activation of regulatory, effector, and innate immune pathways. Given the small sample size, these findings should be considered hypothesis-generating, requiring validation in larger cohorts.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"86 1","pages":"2620127"},"PeriodicalIF":12.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021680","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}
Pub Date : 2026-01-23DOI: 10.1080/19490976.2026.2614054
Eunike Tiffany,Kyoung Su Kim,Panida Sittipo,Dong-Woo Lee,Yun Kyung Lee
Akkermansia muciniphila, Bacteroides thetaiotaomicron, Mediterraneibacter (formerly Ruminococcus) gnavus, and other mucin-degrading (MD) bacteria play pivotal roles in shaping gut microbial ecosystems, maintaining gut barrier function, and mediating host-microbiota crosstalk. These bacteria influence intestinal homeostasis by modulating epithelial cell differentiation, immune responses, and gut microbiota composition through mucin degradation and the production of bioactive metabolites. Their abundance and functional activities fluctuate dynamically in response to dietary components, host immunity, and environmental factors, resulting in context-dependent effects on gastrointestinal and systemic health. This review summarizes current insights into the ecology and metabolic capabilities of MD bacteria, highlighting their dual roles in metabolic disorders, inflammatory diseases, infection susceptibility, and neuroimmune conditions. Understanding the ecological niches and molecular interactions of MD bacteria offers promising approaches for microbiota-targeted therapies aimed at restoring gut and systemic homeostasis.
{"title":"Mucin-degrading gut bacteria: context-dependent roles in intestinal homeostasis and disease.","authors":"Eunike Tiffany,Kyoung Su Kim,Panida Sittipo,Dong-Woo Lee,Yun Kyung Lee","doi":"10.1080/19490976.2026.2614054","DOIUrl":"https://doi.org/10.1080/19490976.2026.2614054","url":null,"abstract":"Akkermansia muciniphila, Bacteroides thetaiotaomicron, Mediterraneibacter (formerly Ruminococcus) gnavus, and other mucin-degrading (MD) bacteria play pivotal roles in shaping gut microbial ecosystems, maintaining gut barrier function, and mediating host-microbiota crosstalk. These bacteria influence intestinal homeostasis by modulating epithelial cell differentiation, immune responses, and gut microbiota composition through mucin degradation and the production of bioactive metabolites. Their abundance and functional activities fluctuate dynamically in response to dietary components, host immunity, and environmental factors, resulting in context-dependent effects on gastrointestinal and systemic health. This review summarizes current insights into the ecology and metabolic capabilities of MD bacteria, highlighting their dual roles in metabolic disorders, inflammatory diseases, infection susceptibility, and neuroimmune conditions. Understanding the ecological niches and molecular interactions of MD bacteria offers promising approaches for microbiota-targeted therapies aimed at restoring gut and systemic homeostasis.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"64 1","pages":"2614054"},"PeriodicalIF":12.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021683","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：