Pub Date : 2026-01-23DOI: 10.1080/19490976.2026.2615494
Shuyu Guo,Bingyong Mao,Xin Tang,Qiuxiang Zhang,Jianxin Zhao,Wei Chen,Shumao Cui
In natural and engineered ecosystems, diverse species interact in complex ways to form highly efficient microecologies. One key orchestrator of these interactions is autoinducer-2 (AI-2), a signaling molecule that plays a crucial role in microbial community assembly, metabolic flux, and resilience to environmental disturbances. This review provides the systematic synthesis of AI-2's dual structural dynamics (S-THMF-borate/R-THMF interconversion) and its context-dependent roles in mediating bacterial crosstalk. It also reveals the receptor diversity (such as LuxP and LsrB) of AI-2 in bacterial kingdom and the signal transduction mechanism. Systematically elaborated on AI-2's regulation of cellular metabolic flux and its ability to autonomously exhibit a series of coordinated behaviors in response to environmental changes. The review explores the ramifications of AI-2 on bacterial community interactions in synthetic biology and natural ecosystems. The wide application of AI-2-mediated interspecific communication in various fields including host health, agriculture, industry and environmental ecology has also been widely discussed. Factors influencing AI-2 production are thoroughly examined, including internal factors such as strain specificity, cell density, growth form and the phenotypic heterogeneity. Additionally, external biological factors (such as nutritional status and environmental stress) and abiotic factors (aggregation, diffusion, and flow) are discussed in detail. By examining knowledge gaps in AI-2-mediated spatial heterogeneity and multi-QS system coordination, this work charts a roadmap for harnessing microbial communication in chemical engineering and environmental sustainability.
{"title":"Autoinducer 2 as a universal language in microbial consortia: decoding molecular mechanisms, ecological impacts, and application.","authors":"Shuyu Guo,Bingyong Mao,Xin Tang,Qiuxiang Zhang,Jianxin Zhao,Wei Chen,Shumao Cui","doi":"10.1080/19490976.2026.2615494","DOIUrl":"https://doi.org/10.1080/19490976.2026.2615494","url":null,"abstract":"In natural and engineered ecosystems, diverse species interact in complex ways to form highly efficient microecologies. One key orchestrator of these interactions is autoinducer-2 (AI-2), a signaling molecule that plays a crucial role in microbial community assembly, metabolic flux, and resilience to environmental disturbances. This review provides the systematic synthesis of AI-2's dual structural dynamics (S-THMF-borate/R-THMF interconversion) and its context-dependent roles in mediating bacterial crosstalk. It also reveals the receptor diversity (such as LuxP and LsrB) of AI-2 in bacterial kingdom and the signal transduction mechanism. Systematically elaborated on AI-2's regulation of cellular metabolic flux and its ability to autonomously exhibit a series of coordinated behaviors in response to environmental changes. The review explores the ramifications of AI-2 on bacterial community interactions in synthetic biology and natural ecosystems. The wide application of AI-2-mediated interspecific communication in various fields including host health, agriculture, industry and environmental ecology has also been widely discussed. Factors influencing AI-2 production are thoroughly examined, including internal factors such as strain specificity, cell density, growth form and the phenotypic heterogeneity. Additionally, external biological factors (such as nutritional status and environmental stress) and abiotic factors (aggregation, diffusion, and flow) are discussed in detail. By examining knowledge gaps in AI-2-mediated spatial heterogeneity and multi-QS system coordination, this work charts a roadmap for harnessing microbial communication in chemical engineering and environmental sustainability.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"321 1","pages":"2615494"},"PeriodicalIF":12.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021682","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}
Excess energy intake contributes to adiposity in obesity. We investigated whether the human intestinal bacterium Phascolarctobacterium faecium could prevent obesity via enteroendocrine pathways in a mouse model of diet-induced obesity (DIO). Daily administration of P. faecium (2 × 109 cells/mouse) reduced food intake through the early overproduction of the satiety hormone peptide YY (PYY) compared to untreated DIO mice. Moreover, P. faecium increased the intestinal levels of branched-chain amino acids, which, in turn, stimulated PYY secretion in neuroendocrine cell cultures and also modified gut microbiota composition. A pair-feeding study demonstrated that the anorexigenic effect of P. faecium contributes to its effects in attenuating body weight gain in DIO mice, but that other mechanisms are also involved in its metabolic benefits. Specifically, P. faecium accelerated gut transit and serum lipid clearance, thereby limiting adiposity independently of food intake. This study identifies the mode of action of a human intestinal bacterium recently linked to obesity protection, providing valuable insights into host-microbe interactions governing body weight.
{"title":"Phascolarctobacterium faecium reduces food intake via PYY signaling, contributing to the mitigation of body weight gain in diet-induced obese mice.","authors":"Clara Bullich-Vilarrubias,Marina Romaní-Pérez,Inmaculada López-Almela,Carlos Pomares-Díaz,Silvia Basili Franzin,Giuseppe Esposito,Alfonso Benítez-Páez,Verónica Tolosa-Enguís,Yolanda Sanz","doi":"10.1080/19490976.2026.2617691","DOIUrl":"https://doi.org/10.1080/19490976.2026.2617691","url":null,"abstract":"Excess energy intake contributes to adiposity in obesity. We investigated whether the human intestinal bacterium Phascolarctobacterium faecium could prevent obesity via enteroendocrine pathways in a mouse model of diet-induced obesity (DIO). Daily administration of P. faecium (2 × 109 cells/mouse) reduced food intake through the early overproduction of the satiety hormone peptide YY (PYY) compared to untreated DIO mice. Moreover, P. faecium increased the intestinal levels of branched-chain amino acids, which, in turn, stimulated PYY secretion in neuroendocrine cell cultures and also modified gut microbiota composition. A pair-feeding study demonstrated that the anorexigenic effect of P. faecium contributes to its effects in attenuating body weight gain in DIO mice, but that other mechanisms are also involved in its metabolic benefits. Specifically, P. faecium accelerated gut transit and serum lipid clearance, thereby limiting adiposity independently of food intake. This study identifies the mode of action of a human intestinal bacterium recently linked to obesity protection, providing valuable insights into host-microbe interactions governing body weight.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"37 1","pages":"2617691"},"PeriodicalIF":12.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014927","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 : 2026-01-20DOI: 10.1080/19490976.2026.2617699
Jing Xu,Ziyi Han,Qing Xue,Haoran Wang,Jiyu Song,Yutong Li,Yongfeng Zhang,Di Wang,Min Hu
The link between hyperlipidemia and periodontitis is well-established, but the underlying mechanisms remain incompletely understood. Here, we reveal a critical role for a 'gut-oral' axis in mediating this interaction. Integrating multi-omics analyses of clinical samples and mouse models, we identified that a significant reduction of intestinal Limosilactobacillus mucosae is a key feature of hyperlipidemic periodontitis (HPD). Fecal microbiota transplantation established a causal link between this gut dysbiosis and exacerbated periodontitis. Mechanistically, oral administration of live L. mucosae ameliorates HPD by restoring intestinal levels of the key metabolite, glycerophosphocholine (α-GPC). Notably, supplementation with α-GPC alone recapitulated this protective effect by upregulating the tight junction protein Claudin-1 (CLDN1) in periodontal tissue. This reinforcement of the epithelial barrier curtailed inflammatory infiltration and restored bone homeostasis. Our findings uncover a protective 'L. mucosae-α-GPC-CLDN1' axis, providing mechanistic insight into how gut microbiota mediates metabolism-associated inflammation and proposing a potential therapeutic strategy for HPD.
{"title":"Limosilactobacillus mucosae attenuates hyperlipidemic periodontitis via the gut-oral axis.","authors":"Jing Xu,Ziyi Han,Qing Xue,Haoran Wang,Jiyu Song,Yutong Li,Yongfeng Zhang,Di Wang,Min Hu","doi":"10.1080/19490976.2026.2617699","DOIUrl":"https://doi.org/10.1080/19490976.2026.2617699","url":null,"abstract":"The link between hyperlipidemia and periodontitis is well-established, but the underlying mechanisms remain incompletely understood. Here, we reveal a critical role for a 'gut-oral' axis in mediating this interaction. Integrating multi-omics analyses of clinical samples and mouse models, we identified that a significant reduction of intestinal Limosilactobacillus mucosae is a key feature of hyperlipidemic periodontitis (HPD). Fecal microbiota transplantation established a causal link between this gut dysbiosis and exacerbated periodontitis. Mechanistically, oral administration of live L. mucosae ameliorates HPD by restoring intestinal levels of the key metabolite, glycerophosphocholine (α-GPC). Notably, supplementation with α-GPC alone recapitulated this protective effect by upregulating the tight junction protein Claudin-1 (CLDN1) in periodontal tissue. This reinforcement of the epithelial barrier curtailed inflammatory infiltration and restored bone homeostasis. Our findings uncover a protective 'L. mucosae-α-GPC-CLDN1' axis, providing mechanistic insight into how gut microbiota mediates metabolism-associated inflammation and proposing a potential therapeutic strategy for HPD.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"6 1","pages":"2617699"},"PeriodicalIF":12.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005013","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 impact of microplastics (MPs) on the diversity and composition of the gut microbiome has been extensively documented in animal studies, but evidence in humans remains limited. Recognizing the potential differences in MP effects between animal and human gut microbiomes, this review synthesizes current evidence concerning their impact on the human gut microbiota. Furthermore, the potential links between microplastic-induced dysbiosis and the pathogenesis of human diseases were analyzed. Cross-sectional studies have been conducted to explore microplastic exposures (such as in humans who consume hot foods served in disposable plastic tableware) and their associations with gut microbiome functionalities in infants, preschool children and adults. Exposure to MPs increased the abundance of Dethiosulfovibrionaceae, Enterobacteriaceae, Moraxellaceae, Actinomycetota, Pseudomonadota, and Veillonella. On the other hand, MPs decreased the abundances of Bacillota, Bacteroidota, Lactobacillales, Rikenellaceae, Parabacteroides, Roseburia, Coprococcus, Turicibacter, and Eubacterium coprostanoligenes. These changes were associated with a decrease in butyrate production and a decrease in short-chain fatty acid levels. However, for some other bacteria, both inductive (on Oscillospiraceae, Adlercreutzia, Phascolarctobacterium, and Collinsella) and repressive effects (on Streptococcus) have been documented. There are contradictory reports about MP-induced changes in Lachnospiraceae (including the Dorea genus), Alistipes and Faecalibacterium, which may be correlated with obesity, gastrointestinal dysfunction, some cancers, inflammatory bowel disease and Crohn's disease. Potential reasons for these discrepancies are proposed. This review also examines putative mechanisms, with a focus on biofilm formation on selective surfaces, and discusses the inherent limitations of current MP exposure assessments in human gut microbiota studies.
{"title":"Gut microbiome remodeling induced by microplastic exposure in humans.","authors":"Xin-Yue Yang,Zhong-Wei Zhang,Guang-Deng Chen,Shu Yuan","doi":"10.1080/19490976.2026.2617696","DOIUrl":"https://doi.org/10.1080/19490976.2026.2617696","url":null,"abstract":"The impact of microplastics (MPs) on the diversity and composition of the gut microbiome has been extensively documented in animal studies, but evidence in humans remains limited. Recognizing the potential differences in MP effects between animal and human gut microbiomes, this review synthesizes current evidence concerning their impact on the human gut microbiota. Furthermore, the potential links between microplastic-induced dysbiosis and the pathogenesis of human diseases were analyzed. Cross-sectional studies have been conducted to explore microplastic exposures (such as in humans who consume hot foods served in disposable plastic tableware) and their associations with gut microbiome functionalities in infants, preschool children and adults. Exposure to MPs increased the abundance of Dethiosulfovibrionaceae, Enterobacteriaceae, Moraxellaceae, Actinomycetota, Pseudomonadota, and Veillonella. On the other hand, MPs decreased the abundances of Bacillota, Bacteroidota, Lactobacillales, Rikenellaceae, Parabacteroides, Roseburia, Coprococcus, Turicibacter, and Eubacterium coprostanoligenes. These changes were associated with a decrease in butyrate production and a decrease in short-chain fatty acid levels. However, for some other bacteria, both inductive (on Oscillospiraceae, Adlercreutzia, Phascolarctobacterium, and Collinsella) and repressive effects (on Streptococcus) have been documented. There are contradictory reports about MP-induced changes in Lachnospiraceae (including the Dorea genus), Alistipes and Faecalibacterium, which may be correlated with obesity, gastrointestinal dysfunction, some cancers, inflammatory bowel disease and Crohn's disease. Potential reasons for these discrepancies are proposed. This review also examines putative mechanisms, with a focus on biofilm formation on selective surfaces, and discusses the inherent limitations of current MP exposure assessments in human gut microbiota studies.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"41 1","pages":"2617696"},"PeriodicalIF":12.2,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994918","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 incidence of type 1 diabetes (T1D) has risen sharply in recent decades, implicating the role of environmental factors in disease pathogenesis. Diet, a primary driver of gut microbiome development and composition, along with other environmental exposures, has emerged as a potential modulator of T1D risk and progression. While nutrients, such as certain vitamins, may exert protective effects, the roles of other dietary factors (e.g., early exposure to dietary antigens) remain unclear. Importantly, diet shapes the gut microbiome, which produces immunomodulatory metabolites, including secondary bile acids, short-chain fatty acids (SCFAs), and others that directly influence immune responses. This review presents evidence on how specific dietary factors, including macronutrients (fats, carbohydrates, proteins, such as gluten and milk proteins), fibers, and breastfeeding, affect the gut microbiome and T1D. We also discuss the effects of microbiome-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, on T1D and their potential as future therapeutic strategies. Although animal studies provide compelling mechanistic insights, the results from human trials remain inconsistent, underscoring the urgent need for longitudinal and interventional studies to establish causality. Understanding the complex interplay between diet, the gut microbiome, and immune homeostasis is essential for developing personalized strategies to prevent and treat T1D and delay-related complications.
{"title":"Diet, gut microbiome, and type 1 diabetes: from risk to translational opportunity.","authors":"Khyati Girdhar,Sandra Dedrick,Lukas Rhodes,David Kim,Amaya Powis,Caitlin Mahon,Hannah Chapdelaine,Liane Obaid,Meghan McNamara,Emrah Altindis","doi":"10.1080/19490976.2026.2614039","DOIUrl":"https://doi.org/10.1080/19490976.2026.2614039","url":null,"abstract":"The incidence of type 1 diabetes (T1D) has risen sharply in recent decades, implicating the role of environmental factors in disease pathogenesis. Diet, a primary driver of gut microbiome development and composition, along with other environmental exposures, has emerged as a potential modulator of T1D risk and progression. While nutrients, such as certain vitamins, may exert protective effects, the roles of other dietary factors (e.g., early exposure to dietary antigens) remain unclear. Importantly, diet shapes the gut microbiome, which produces immunomodulatory metabolites, including secondary bile acids, short-chain fatty acids (SCFAs), and others that directly influence immune responses. This review presents evidence on how specific dietary factors, including macronutrients (fats, carbohydrates, proteins, such as gluten and milk proteins), fibers, and breastfeeding, affect the gut microbiome and T1D. We also discuss the effects of microbiome-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, on T1D and their potential as future therapeutic strategies. Although animal studies provide compelling mechanistic insights, the results from human trials remain inconsistent, underscoring the urgent need for longitudinal and interventional studies to establish causality. Understanding the complex interplay between diet, the gut microbiome, and immune homeostasis is essential for developing personalized strategies to prevent and treat T1D and delay-related complications.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"141 1","pages":"2614039"},"PeriodicalIF":12.2,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968388","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 : 2026-01-13DOI: 10.1080/19490976.2025.2611544
Hyeon Gwon Lee,Ju Yeon Song,Jaekyung Yoon,Yusook Chung,Soon-Kyeong Kwon,Jihyun F Kim
Metagenomic approaches offer unprecedented opportunities to characterize microbial community structure and function, yet several challenges remain unresolved. Inconsistent genome quality impairs reliability of metagenome-assembled genomes, lack of unified taxonomic criteria limits cross-study comparability, and multi-step workflows involving numerous programs and parameters hinder reproducibility and accessibility. We benchmarked existing programs and parameters using simulated metagenomic data to identify optimal configurations. metaFun is an open-source, end-to-end pipeline that integrates quality control, taxonomic profiling, functional profiling, de novo assembly, binning, genome assessment, comparative genomic analysis, pangenome annotation, network analysis, and strain-level microdiversity analysis into a unified framework. Interactive modules support standardized data interpretation and exploratory visualization. The pipeline is implemented with Nextflow and containerized with Apptainer, ensuring environment reproducibility and scalability. Comprehensive documentation is available at https://metafun-doc.readthedocs.io/en/main. The pipeline was validated using a colorectal cancer cohort dataset. By addressing key methodological gaps, metaFun facilitates accessible and reproducible metagenomic analysis for the broader research community.
{"title":"metaFun: An analysis pipeline for metagenomic big data with fast and unified functional searches.","authors":"Hyeon Gwon Lee,Ju Yeon Song,Jaekyung Yoon,Yusook Chung,Soon-Kyeong Kwon,Jihyun F Kim","doi":"10.1080/19490976.2025.2611544","DOIUrl":"https://doi.org/10.1080/19490976.2025.2611544","url":null,"abstract":"Metagenomic approaches offer unprecedented opportunities to characterize microbial community structure and function, yet several challenges remain unresolved. Inconsistent genome quality impairs reliability of metagenome-assembled genomes, lack of unified taxonomic criteria limits cross-study comparability, and multi-step workflows involving numerous programs and parameters hinder reproducibility and accessibility. We benchmarked existing programs and parameters using simulated metagenomic data to identify optimal configurations. metaFun is an open-source, end-to-end pipeline that integrates quality control, taxonomic profiling, functional profiling, de novo assembly, binning, genome assessment, comparative genomic analysis, pangenome annotation, network analysis, and strain-level microdiversity analysis into a unified framework. Interactive modules support standardized data interpretation and exploratory visualization. The pipeline is implemented with Nextflow and containerized with Apptainer, ensuring environment reproducibility and scalability. Comprehensive documentation is available at https://metafun-doc.readthedocs.io/en/main. The pipeline was validated using a colorectal cancer cohort dataset. By addressing key methodological gaps, metaFun facilitates accessible and reproducible metagenomic analysis for the broader research community.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"13 1","pages":"2611544"},"PeriodicalIF":12.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961499","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 : 2026-01-13DOI: 10.1080/19490976.2026.2614030
Emily Connell,Gwénaëlle Le Gall,Simon McArthur,Leonie Lang,Bernadette Breeze,Marrium Liaquat,Matthew G Pontifex,Saber Sami,Line Pourtau,David Gaudout,Michael Müller,David Vauzour
BACKGROUNDAlzheimer's disease (AD) is projected to increase in prevalence, heightening the need for strategies to alleviate its neuropathological burden. The bioactive constituents of a Mediterranean-style diet are well-recognised for their neuroprotective properties. Due to their capacity to alter the gut microbiome composition, these benefits may involve modulation of the microbiota-gut-brain axis. In this study, we investigated whether a novel supplement enriched with key Mediterranean diet-derived bioactives (Neurosyn240) could reduce amyloid deposition and microglial activation in 5xFAD mice, a transgenic model of AD, through microbiota-mediated mechanisms.METHODSMale and female 5xFAD transgenic mice (n = 16 per sex) were randomly assigned to receive either a standard control diet or a diet supplemented with Neurosyn240 for 12 weeks. Employing a multi-omics approach, gut microbiota composition was profiled using 16S rRNA ampliconsequencing, serum metabolites were quantified via targeted metabolomics, and hippocampal gene expression was analysed through qPCR and RNA sequencing. Neuropathological markers, including amyloid-β deposition and microglial activation, were evaluated using immunofluorescence staining. Statistical analyses were performed using two-way ANOVA to examine the main effects of diet and sex and their interaction.RESULTSNeurosyn240 significantly shifted the gut microbiome composition, which was associated with increased circulatory serotonin levels and decreased kynurenine and bile acids (TCA, HDCA, TDCA, CDCA and LCA) concentrations. In the brain, Neurosyn240 consumption led to a significant reduction in hippocampal amyloid deposits and Iba-1 positive microglia (p<0.05), which were associated with decreased LCA and increased serotonin, respectively. Hippocampal RNA sequencing further highlighted the upregulation of genes involved in promoting amyloid beta clearance mechanisms.CONCLUSIONSTogether, these findings highlight novel neuroprotective effects of Neurosyn240 in modulating metabolite-mediated pathways of the microbiota-gut-brain axis, accentuating its therapeutic potential against AD progression.
{"title":"A novel Mediterranean diet-inspired supplement reduces hippocampal amyloid deposits and microglial activation through the modulation of the microbiota gut-brain axis in 5xFAD mice.","authors":"Emily Connell,Gwénaëlle Le Gall,Simon McArthur,Leonie Lang,Bernadette Breeze,Marrium Liaquat,Matthew G Pontifex,Saber Sami,Line Pourtau,David Gaudout,Michael Müller,David Vauzour","doi":"10.1080/19490976.2026.2614030","DOIUrl":"https://doi.org/10.1080/19490976.2026.2614030","url":null,"abstract":"BACKGROUNDAlzheimer's disease (AD) is projected to increase in prevalence, heightening the need for strategies to alleviate its neuropathological burden. The bioactive constituents of a Mediterranean-style diet are well-recognised for their neuroprotective properties. Due to their capacity to alter the gut microbiome composition, these benefits may involve modulation of the microbiota-gut-brain axis. In this study, we investigated whether a novel supplement enriched with key Mediterranean diet-derived bioactives (Neurosyn240) could reduce amyloid deposition and microglial activation in 5xFAD mice, a transgenic model of AD, through microbiota-mediated mechanisms.METHODSMale and female 5xFAD transgenic mice (n = 16 per sex) were randomly assigned to receive either a standard control diet or a diet supplemented with Neurosyn240 for 12 weeks. Employing a multi-omics approach, gut microbiota composition was profiled using 16S rRNA ampliconsequencing, serum metabolites were quantified via targeted metabolomics, and hippocampal gene expression was analysed through qPCR and RNA sequencing. Neuropathological markers, including amyloid-β deposition and microglial activation, were evaluated using immunofluorescence staining. Statistical analyses were performed using two-way ANOVA to examine the main effects of diet and sex and their interaction.RESULTSNeurosyn240 significantly shifted the gut microbiome composition, which was associated with increased circulatory serotonin levels and decreased kynurenine and bile acids (TCA, HDCA, TDCA, CDCA and LCA) concentrations. In the brain, Neurosyn240 consumption led to a significant reduction in hippocampal amyloid deposits and Iba-1 positive microglia (p<0.05), which were associated with decreased LCA and increased serotonin, respectively. Hippocampal RNA sequencing further highlighted the upregulation of genes involved in promoting amyloid beta clearance mechanisms.CONCLUSIONSTogether, these findings highlight novel neuroprotective effects of Neurosyn240 in modulating metabolite-mediated pathways of the microbiota-gut-brain axis, accentuating its therapeutic potential against AD progression.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"385 1","pages":"2614030"},"PeriodicalIF":12.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956206","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 : 2026-01-13DOI: 10.1080/19490976.2026.2614451
Pu Yang,Yifei Pei,Yongqi Huang,Mengyuan Dong,Fangming Cui,Shuang Nie,Xuan Zhang,Fenglin Cao
Early life gut microbiota function as biological sensors for maternal prenatal exposure and play a crucial role in infant neurodevelopment. During pregnancy, air pollution and psychological distress are regarded as general and specific external exposures, respectively; however, the joint influence of these two domains on shaping early life gut microbiota remains unexplored. In this study, 309 mother-infant pairs were recruited from the obstetrics departments of two tertiary hospitals. We collected data on maternal prenatal air pollution exposure and psychological distress, obtained meconium samples within 48 h after birth, and assessed infant neurodevelopmental outcomes using the Ages and Stages Questionnaire-3 at 1, 3, and 6 months postpartum. Maternal prenatal air pollution-psychological distress exposure patterns were identified using a self-organizing map (SOM). The differential features of the meconium microbiota in relation to co-exposure patterns were assessed using multivariate association of linear models. Finally, the mediating role of the meconium microbiota in co-exposure patterns and infant neurodevelopment was analyzed using mediation analysis. We observed that the meconium microbiota at both the phylum and genus levels differed among the three patterns. Ruminococcus mediated the relationship between co-exposure patterns and infant neurodevelopment at 3 months of age (IE = 0.181-0.261, pFDR < 0.001). These findings support the inclusion of infant gut microbiota within frameworks assessing the risks of maternal prenatal co-exposure to environmental pollution and psychological distress, providing a scientific basis for policymakers to identify intervention targets for high-risk populations.
{"title":"Maternal prenatal co-exposure to air pollution and psychological distress shapes the neonatal gut: microbiota-mediated pathways to early neurodevelopment.","authors":"Pu Yang,Yifei Pei,Yongqi Huang,Mengyuan Dong,Fangming Cui,Shuang Nie,Xuan Zhang,Fenglin Cao","doi":"10.1080/19490976.2026.2614451","DOIUrl":"https://doi.org/10.1080/19490976.2026.2614451","url":null,"abstract":"Early life gut microbiota function as biological sensors for maternal prenatal exposure and play a crucial role in infant neurodevelopment. During pregnancy, air pollution and psychological distress are regarded as general and specific external exposures, respectively; however, the joint influence of these two domains on shaping early life gut microbiota remains unexplored. In this study, 309 mother-infant pairs were recruited from the obstetrics departments of two tertiary hospitals. We collected data on maternal prenatal air pollution exposure and psychological distress, obtained meconium samples within 48 h after birth, and assessed infant neurodevelopmental outcomes using the Ages and Stages Questionnaire-3 at 1, 3, and 6 months postpartum. Maternal prenatal air pollution-psychological distress exposure patterns were identified using a self-organizing map (SOM). The differential features of the meconium microbiota in relation to co-exposure patterns were assessed using multivariate association of linear models. Finally, the mediating role of the meconium microbiota in co-exposure patterns and infant neurodevelopment was analyzed using mediation analysis. We observed that the meconium microbiota at both the phylum and genus levels differed among the three patterns. Ruminococcus mediated the relationship between co-exposure patterns and infant neurodevelopment at 3 months of age (IE = 0.181-0.261, pFDR < 0.001). These findings support the inclusion of infant gut microbiota within frameworks assessing the risks of maternal prenatal co-exposure to environmental pollution and psychological distress, providing a scientific basis for policymakers to identify intervention targets for high-risk populations.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"35 1","pages":"2614451"},"PeriodicalIF":12.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961498","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 : 2026-01-11DOI: 10.1080/19490976.2025.2609457
Maarten van de Guchte,Stanislas Mondot,Julie Cadiou,Ruma Raghuvanshi,Colombe Rous,Joël Doré
Fecal microbiota transfer (FMT) has been used with variable success in the experimental treatment of ulcerative colitis (UC), and efforts to improve its efficacy very much remain a matter of trial and error. We recently predicted that atypical donor microbiota could improve results. Here, we provide experimental support for this prediction in a rat model where we induced a transition of the intestinal ecosystem to an alternative state characterized by chronic low-grade inflammation and dysbiosis. While autologous FMT did barely or not enhance the restoration of a healthy microbiota compared to a control group without FMT, the atypical allogenic microbiota from one of two donor rat strains proved remarkably successful in the restoration of a healthy microbiota, in some cases accompanied by a healthy distal colon histology. These results allow the rationalization of research efforts towards improvement of FMT efficacy in humans, and indicate that (initial) success of FMT should be monitored at the microbiota level as much as at the level of clinical symptoms. More importantly, they provide further support for our earlier published, clinical-data-based, conceptual model of the intestinal ecosystem which suggests promising opportunities for therapeutic innovation in UC treatment. This model notably predicts that, and explains why, symbio-therapy, acting on both microbiota and inflammation, may be more efficient than conventional inflammation-directed therapies, and can be used to guide and monitor treatments.
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Pub Date : 2026-01-11DOI: 10.1080/19490976.2025.2611617
Tony W H Tang,Kiramat Ullah,Jia-Jung Lee,Hung-Chih Chen,Patrick C H Hsieh
Gut microbiota research has rapidly expanded our understanding of host-microbe interactions in cardiovascular diseases, yet translation of these insights remains challenged by species-specific differences and substantial population heterogeneity. In this review, we synthesize current evidence across rodents, swine, non-human primates, and multi-ethnic human cohorts to delineate conserved versus context-dependent features of the gut-heart axis. Rodent models remain indispensable for mechanistic discovery, enabling causal testing through germ-free, antibiotic-treated, and humanized microbiota platforms, whereas large-animal models better replicate human cardiac anatomy, physiology, and microbial ecology. Human studies provide essential clinical relevance, demonstrating that patients with myocardial infarction, coronary artery disease, atrial fibrillation, and heart failure harbor distinct microbial and metabolite signatures. However, these findings vary across populations due to differences in diet, lifestyle, host genetics, medication exposure, and environmental transitions. Despite taxonomic variability, several functional pathways, most notably short-chain fatty acid production, bile acid biotransformation, and aromatic amino acid metabolism generating molecules such as trimethylamine-N-oxide and phenylacetylglutamine, consistently associate with cardiovascular risk. At the same time, population-specific features, including glycan-microbe interactions shaped by ABO and FUT2 genotypes, diet-responsive metabolite profiles, and variable drug-microbiome interactions, highlight the importance of genetic and environmental context. By integrating cross-species and cross-population evidence, this review outlines a framework for identifying robust microbial pathways, clarifying their translational boundaries, and guiding the development of microbiota-informed diagnostics and interventions that account for biological, cultural, and environmental diversity.
肠道菌群研究迅速扩展了我们对心血管疾病中宿主-微生物相互作用的理解，但这些见解的翻译仍然受到物种特异性差异和大量种群异质性的挑战。在这篇综述中，我们综合了啮齿类动物、猪、非人类灵长类动物和多种族人类群体的现有证据，以描绘肠-心轴的保守特征与环境依赖特征。啮齿动物模型对于机制发现仍然是不可或缺的，可以通过无菌、抗生素治疗和人源化的微生物群平台进行因果检验，而大型动物模型可以更好地复制人类心脏解剖、生理和微生物生态。人体研究提供了必要的临床相关性，证明心肌梗死、冠状动脉疾病、心房颤动和心力衰竭患者具有不同的微生物和代谢物特征。然而，由于饮食、生活方式、宿主遗传、药物暴露和环境转变的差异，这些发现在人群中有所不同。尽管分类上存在差异，但一些功能途径，尤其是短链脂肪酸产生、胆酸生物转化和芳香族氨基酸代谢产生的分子，如三甲胺- n -氧化物和苯乙酰谷氨酰胺，始终与心血管风险相关。与此同时，人群特异性特征，包括ABO和FUT2基因型形成的聚糖-微生物相互作用，饮食反应代谢物谱和可变的药物-微生物相互作用，突出了遗传和环境背景的重要性。通过整合跨物种和跨种群的证据，本综述概述了一个框架，用于识别强大的微生物途径，澄清其翻译边界，并指导微生物群诊断和干预措施的发展，以解释生物，文化和环境多样性。
{"title":"Comparative insights into the gut-heart axis: cross-species and cross-population perspectives.","authors":"Tony W H Tang,Kiramat Ullah,Jia-Jung Lee,Hung-Chih Chen,Patrick C H Hsieh","doi":"10.1080/19490976.2025.2611617","DOIUrl":"https://doi.org/10.1080/19490976.2025.2611617","url":null,"abstract":"Gut microbiota research has rapidly expanded our understanding of host-microbe interactions in cardiovascular diseases, yet translation of these insights remains challenged by species-specific differences and substantial population heterogeneity. In this review, we synthesize current evidence across rodents, swine, non-human primates, and multi-ethnic human cohorts to delineate conserved versus context-dependent features of the gut-heart axis. Rodent models remain indispensable for mechanistic discovery, enabling causal testing through germ-free, antibiotic-treated, and humanized microbiota platforms, whereas large-animal models better replicate human cardiac anatomy, physiology, and microbial ecology. Human studies provide essential clinical relevance, demonstrating that patients with myocardial infarction, coronary artery disease, atrial fibrillation, and heart failure harbor distinct microbial and metabolite signatures. However, these findings vary across populations due to differences in diet, lifestyle, host genetics, medication exposure, and environmental transitions. Despite taxonomic variability, several functional pathways, most notably short-chain fatty acid production, bile acid biotransformation, and aromatic amino acid metabolism generating molecules such as trimethylamine-N-oxide and phenylacetylglutamine, consistently associate with cardiovascular risk. At the same time, population-specific features, including glycan-microbe interactions shaped by ABO and FUT2 genotypes, diet-responsive metabolite profiles, and variable drug-microbiome interactions, highlight the importance of genetic and environmental context. By integrating cross-species and cross-population evidence, this review outlines a framework for identifying robust microbial pathways, clarifying their translational boundaries, and guiding the development of microbiota-informed diagnostics and interventions that account for biological, cultural, and environmental diversity.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"39 1","pages":"2611617"},"PeriodicalIF":12.2,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949718","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}
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