MicrobiomePub Date : 2026-07-23DOI: 10.1186/s40168-026-02462-1
Matthew Chung, Clea R Barnett, Lars Hunger, Imran Sulaiman, Benjamin G Wu, Yonghua Li, Jun-Chieh J Tsay, Shari B Brosnahan, Cecilia J Chung, Luis Angel, Gregg J Silverman, James T Morton, Leopoldo N Segal, Elodie Ghedin
{"title":"Immunosuppression is associated with loss of airway microbiome resilience in severe COVID-19.","authors":"Matthew Chung, Clea R Barnett, Lars Hunger, Imran Sulaiman, Benjamin G Wu, Yonghua Li, Jun-Chieh J Tsay, Shari B Brosnahan, Cecilia J Chung, Luis Angel, Gregg J Silverman, James T Morton, Leopoldo N Segal, Elodie Ghedin","doi":"10.1186/s40168-026-02462-1","DOIUrl":"https://doi.org/10.1186/s40168-026-02462-1","url":null,"abstract":"<p><strong>Background: </strong>The role of the lower airway microbiome in COVID-19-associated mortality remains poorly understood despite evidence implicating secondary pathogens and non-airway commensals. The influence of prior immunosuppression on the lower airway microbiome and its contribution to mortality in mechanically ventilated patients has been largely unexplored. Given that host-microbiome interactions are dynamic, we assessed longitudinal patterns in the respiratory microbiome associated with mortality and immunosuppression status.</p><p><strong>Results: </strong>We conducted longitudinal forecasting, differential abundance, and comparative network analyses of metatranscriptomic data from 604 upper and lower airway samples collected from 243 mechanically ventilated COVID-19 patients to profile key microbial factors associated with immunosuppression and clinical outcome. SARS-CoV-2 was enriched over time in immunosuppressed patients and in both immunosuppressed and immunocompetent patients who died, highlighting the need for aggressive viral infection control early in the disease course. Using longitudinal forecasting and differential abundance analyses, we observed a progressive increase in opportunistic pathogens, such as Staphylococcus aureus and Escherichia coli, among the taxa most predictive of mortality. Concurrently, immunosuppressed individuals exhibited a significant decrease in typical airway commensals alongside a restructuring and marked destabilization of the microbial community compared with their immunocompetent counterparts.</p><p><strong>Conclusions: </strong>These findings indicate that loss of airway microbiome stability in immunosuppressed patients constitutes an independent factor contributing to increased susceptibility to opportunistic pathogens and poor clinical outcomes. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"14 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2026-07-22DOI: 10.1186/s40168-026-02468-9
Line Fisker Zachariassen, Frederikke Uldall Fløe Mortensen, Caroline Märta Junker Mentzel, Ping-Ping Jiang, Pablo Atienza Lopez, Lukasz Krych, Nuria Canibe, Rikke Kaae Kirk, Andreas Vegge, Morten Arendt Rasmussen, Jakob Stokholm, Camilla Hartmann Friis Hansen
{"title":"Cesarean section-induced changes in the gut microbiota facilitate metabolic disease in high-fat diet-induced obese mice.","authors":"Line Fisker Zachariassen, Frederikke Uldall Fløe Mortensen, Caroline Märta Junker Mentzel, Ping-Ping Jiang, Pablo Atienza Lopez, Lukasz Krych, Nuria Canibe, Rikke Kaae Kirk, Andreas Vegge, Morten Arendt Rasmussen, Jakob Stokholm, Camilla Hartmann Friis Hansen","doi":"10.1186/s40168-026-02468-9","DOIUrl":"10.1186/s40168-026-02468-9","url":null,"abstract":"<p><strong>Background: </strong>The global rate of cesarean section (CS) births is increasing. Growing evidence suggests that CS birth may alter the gut microbiota (i.e., dysbiosis) and increase the risk of immune and metabolic disorders, although confounding factors make causality difficult to establish. The studies presented here aimed to investigate the causal relationship between CS-induced gut dysbiosis and obesity in a diet-induced obese mouse model and explore potential microbiota-targeted therapies.</p><p><strong>Results: </strong>In the first study, male C57BL/6 mice were delivered via CS or vaginally (VD) and fed a high- or low-fat diet (HFD, LFD) for 12 weeks. In the second study, male germ-free BALB/c mice were transplanted with fecal microbiota from 1-month-old infants born by CS or VD and fed a HFD or HFD + human milk oligosaccharides (HMOs) for 16 weeks. CS in mice induced only minor differences in weight gain and had no effect on other metabolic endpoints, likely because there was no difference in the gut microbiota between the CS and VD mice. In contrast, mice colonized with the human CS microbiota weighed significantly more and developed greater insulin resistance than mice colonized with the VD microbiota. These phenotypic changes were accompanied by alterations in serum cytokines, adipokines and metabolic hormones as well as differential gene expression across multiple metabolic tissues. Notably, these manifestations were partially ameliorated by HMO supplementation and by administration of Bacteroides fragilis, a taxon depleted in the CS donor microbiota, which directly reduced circulating FGF-21 levels, implicating this bacterium in host metabolic regulation.</p><p><strong>Conclusions: </strong>CS-induced gut dysbiosis can increase the risk of developing obesity and insulin resistance, but without dysbiosis, the metabolic effects of CS birth in isolation are minimal, suggesting that promising therapeutic targets may be identified in the gut microbiome. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2026-07-21DOI: 10.1186/s40168-026-02470-1
Dan-Yang Cao, Rui-Ting Wu, Huan Du, Mo-Lin Li, Jin-Cheng Ye, Lei Xiang, Nai-Xian Feng, Bai-Lin Liu, Yan-Wen Li, Quan-Ying Cai, Qing X Li, Ce-Hui Mo, Hai-Ming Zhao
{"title":"Rhizobacterial functional assemblies modulate accumulation of phthalates in choysum (Brassica parachinensis L.).","authors":"Dan-Yang Cao, Rui-Ting Wu, Huan Du, Mo-Lin Li, Jin-Cheng Ye, Lei Xiang, Nai-Xian Feng, Bai-Lin Liu, Yan-Wen Li, Quan-Ying Cai, Qing X Li, Ce-Hui Mo, Hai-Ming Zhao","doi":"10.1186/s40168-026-02470-1","DOIUrl":"10.1186/s40168-026-02470-1","url":null,"abstract":"<p><strong>Background: </strong>Rhizomicrobiomes exhibit dynamic adaptability in their structural and functional compositions in response to environmental stressors, playing pivotal roles in modulating host plant tolerance and growth. Nevertheless, the responses of rhizomicrobiomes to pollution stress remain poorly understood. In this study, we investigate how di(2-ethylhexyl) phthalate (DEHP), a widespread soil contaminant, alters the rhizomicrobiomes of two choysum (Brassica parachinensis L.) varieties and how these stress-regulated microbial communities contribute to the distinct response patterns between the low-accumulation variety (LAV) and the high-accumulation variety (HAV).</p><p><strong>Results: </strong>The two choysum varieties exhibited differential recruitment of bacterial taxa in response to DEHP. The DEHP-sensitive LAV variety preferentially recruited DEHP-degrading bacteria, adopting an \"avoidance-like\" pattern to minimize DEHP accumulation. In contrast, the DEHP-tolerant HAV variety recruited plant growth-promoting bacteria, prioritizing growth regardless of DEHP accumulation. Synthetic microbial communities (SynComs) constructed from variety-specific isolates, along with corresponding cross-inoculation experiments, confirmed preferential colonization within host plants and the resulting phenotypic outcomes. These findings suggest that variety-specific rhizomicrobiome assembly confers distinct patterns in response to DEHP contamination, offering a potential mitigation approach to enhance food safety.</p><p><strong>Conclusions: </strong>This study demonstrates variety-specific response patterns to soil organic pollutant (DEHP) from the perspective of rhizosphere microbial assembly, and establishes a direct link between DEHP accumulation phenotypes and functionally divergent rhizobacterial assemblies validated by SynCom experiments. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2026-07-21DOI: 10.1186/s40168-026-02444-3
Yuting Zhai, Yejin Kim, Ga-Hee Ban, Yeo Min Kim, Sam-Churl Kim, Dongryeoul Bae, Kwangcheol C Jeong, Sun Ae Kim
{"title":"Environmental reservoirs and transmission pathways of antimicrobial resistance across the pork production continuum.","authors":"Yuting Zhai, Yejin Kim, Ga-Hee Ban, Yeo Min Kim, Sam-Churl Kim, Dongryeoul Bae, Kwangcheol C Jeong, Sun Ae Kim","doi":"10.1186/s40168-026-02444-3","DOIUrl":"10.1186/s40168-026-02444-3","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance (AMR) is a major One Health challenge linking human, animal, and environmental health, yet the contribution of food production environments to resistance transmission remains poorly understood.</p><p><strong>Results: </strong>We conducted a longitudinal shotgun metagenomic study across the pork production continuum from farm to retail to identify environmental AMR reservoirs and transmission pathways of antimicrobial resistance genes (ARGs). Assembly-based, genome-resolved, and source-tracking analyses were integrated to characterize resistomes, microbial communities, and horizontal gene transfer dynamics. ARG abundance and diversity were highest at farms, slaughterhouses, and processing plants and declined toward retail, although clinically relevant resistance determinants persisted throughout processing. Slaughterhouse environments emerged as major contributors to ARG contamination on carcasses, highlighting the importance of environmental exposure at intermediate stages. Resistome structure was closely linked to microbial community composition, with persistent taxa such as Acinetobacter and Pseudomonas serving as key ARG carriers, including genes conferring resistance to tetracycline, aminoglycosides, macrolide-lincosamide-streptogramin, and β-lactams, multidrug efflux. Co-localization of ARGs with mobile genetic elements demonstrated ongoing potential for horizontal transfer across production stages, and genome-resolved metagenome-assembled genome analyses revealed overlapping resistance and virulence profiles between slaughterhouse- and processing plant-associated bacteria, indicating adaptive persistence within pork production environments.</p><p><strong>Conclusions: </strong>Resistome composition across the pork production chain is largely shaped by stage-specific environmental sources, highlighting potential intervention points to mitigate AMR transmission. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SEVA: structural and evolutionary feature integration for predicting virulence factors and antibiotic resistance genes.","authors":"Kaiqi Li, Xin Peng, Xiuwei Qian, Shuaicheng Li, Xianglilan Zhang","doi":"10.1186/s40168-026-02467-w","DOIUrl":"10.1186/s40168-026-02467-w","url":null,"abstract":"<p><strong>Background: </strong>Infectious diseases continue to pose unprecedented challenges to public health and the global economy. Virulence factors (VFs) enable pathogens to adhere, reproduce, and cause damage to host cells, while antibiotic resistance genes (ARGs) enable pathogens to withstand treatments that would otherwise be effective. The concurrent identification of VFs and ARGs is crucial for efficient pathogen surveillance. However, existing tools for predicting VFs or ARGs typically suffer from high false negative rates and limitations in identifying only high-identity genes against known reference VF or ARG databases.</p><p><strong>Results: </strong>To address these challenges, we developed SEVA, an advanced model that integrates protein language models (pLMs) with structural and evolutionary protein features to predict VFs and ARGs from genome sequencing data. Integrating multiple homologous sequences can identify latent virulence or drug resistance caused by site mutations, reducing false negative rates. Meanwhile, the protein structure remains conserved despite the low sequence identity in some functional domains of VFs or ARGs. The aggregate of protein structure information further improves the identification abilities of VF and ARG. In addition, pLMs enable the model to capture high-dimensional feature representations more effectively. SEVA rigorously collected three datasets with over 20,000 genes and five reference databases. It outperforms state-of-the-art methods, including Diamond, VRprofile, FoldSeek, PreVFs-RG, PLM-ARG, ARG-BERT, and HyperVR, achieving an accuracy of 97.13% and confirming the efficacy of its key components, such as refined feature selection and multiple sequence alignment subsampling.</p><p><strong>Conclusion: </strong>SEVA takes protein sequences as input and derives evolutionary, structural, and statistical representations for prediction, making our model a reliable tool for VF and ARG prediction. This capability is particularly valuable in epidemic prevention and control, where accurate identification of VFs and ARGs is crucial. By providing concurrent and reliable predictions of VFs and ARGs, SEVA enhances our ability to respond to microbial threats effectively. This finding supports robust efforts to mitigate the spread of infectious diseases and safeguard public health, addressing a critical gap in contemporary epidemic response strategies. The SEVA model and data are available at https://github.com/kaiqili2/SEVA . Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2026-07-16DOI: 10.1186/s40168-026-02465-y
Ya-Ning Wang, Jin-Ting Zheng, Xue-Peng Chen, Luo-Qin Shen, Ming-Ming Sun, Mao Ye, Yi-Fei Wang, Roy Neilson, Dong Zhu
{"title":"Invertebrates gut viromes mediate microbial adaptation to pharmaceutical diversity under warming.","authors":"Ya-Ning Wang, Jin-Ting Zheng, Xue-Peng Chen, Luo-Qin Shen, Ming-Ming Sun, Mao Ye, Yi-Fei Wang, Roy Neilson, Dong Zhu","doi":"10.1186/s40168-026-02465-y","DOIUrl":"10.1186/s40168-026-02465-y","url":null,"abstract":"<p><strong>Background: </strong>Pharmaceutical pollution is an emerging environmental concern that can disrupt microbial communities and ecological processes, while climate warming adds further stress with broad ecological consequences. Soil invertebrates such as collembolans harbor gut microbiomes essential for host health and ecosystem stability, yet the responses of these communities-particularly viral communities-to combined pharmaceutical and warming pressures remain unclear. Here, we used controlled microcosm experiments with Folsomia candida to investigate how pharmaceutical diversity and fluctuating warming jointly shape gut microbiomes through bacteria-virus interactions.</p><p><strong>Results: </strong>Pharmaceutical diversity significantly reduced the alpha diversity of gut viral communities in F. candida, an effect not observed in surrounding soils. Diurnal warming increased the proportion of lysogenic phages and enhanced auxiliary metabolic genes (AMGs) such as ACADM and nrdA. Functional validation in Escherichia coli BL21 confirmed that these genes mitigate oxidative stress and improve host thermal tolerance. In contrast, diverse pharmaceuticals increased the proportion of lytic phages, likely driving nutrient turnover through a \"kill-the-winner\" dynamic that stimulated bacterial taxa involved in pharmaceutical degradation. Moreover, warming amplified the disruption of gut bacterial communities caused by pharmaceutical diversity and strengthened bacteria-virus co-occurrence networks.</p><p><strong>Conclusions: </strong>Our findings reveal that gut viruses act as pivotal regulators of microbial adaptation under concurrent chemical and climate stressors. By mediating host resilience and microbial dynamics, the gut virome provides mechanistic insights into ecosystem stability, and may also serve as an early indicator of combined pharmaceutical and warming stress in soil invertebrate systems, underscoring the need to integrate viral-microbial interactions into One Health framework for environmental risk assessment. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Horizontal acquisition of nicotine catabolism gene cluster enhances Arthrobacter fitness within tobacco root microbiota.","authors":"Tomohisa Shimasaki, Yui Nose, Sachiko Masuda, Arisa Shibata, Tsubasa Shoji, Shuhei Yabe, Maiko Furubayashi, Yoshitomo Kikuchi, Ken Shirasu, Kazufumi Yazaki, Yasunori Ichihashi, Akifumi Sugiyama, Ryohei Thomas Nakano","doi":"10.1186/s40168-026-02466-x","DOIUrl":"10.1186/s40168-026-02466-x","url":null,"abstract":"<p><strong>Background: </strong>Plant roots are hotspots for interactions with soil microbes, where a characteristic bacterial community structure is formed. Plant specialized metabolites often play pivotal roles in this assembly process. However, the molecular basis underlying root microbiota responses to these bioactive compounds, and how such metabolic interactions shape the assembly of host-specific root microbiota, remain largely unknown. Nicotine is a toxic alkaloid predominantly produced by the genus Nicotiana, and the genus Arthrobacter is known as one of the nicotine-degrading bacteria in the tobacco root microbiota. In this study, we used the tobacco-Arthrobacter interaction system as a model and integrated comparative genomics and experimental genetic manipulation assays to uncover the role of bacterial catabolism capacity for host specialized metabolites in shaping host-specific root microbiota.</p><p><strong>Results: </strong>Nicotine catabolism genes are uniquely found in the Arthrobacter strains derived from nicotine-containing environments, and this restricted gene distribution is driven by a plasmid-mediated horizontal gene transfer. To assess the ecological consequences of this genomic adaptation in Arthrobacter fitness in tobacco roots, we characterized the nicotine utilization ability of Arthrobacter and conducted adaptation assays under in planta conditions using genetically manipulated Arthrobacter strains and tobacco mutants impaired in nicotine catabolism and biosynthesis, respectively. Nicotine improves Arthrobacter colonization of tobacco roots through a catabolism-dependent mechanism. Bacterial community analysis using a synthetic community approach further demonstrated that this metabolic adaptation enhances Arthrobacter fitness within tobacco root microbiota.</p><p><strong>Conclusions: </strong>Our findings illustrated that bacterial catabolic capacity toward host-derived plant specialized metabolites is key for successful root colonization. This metabolic adaptation is driven by plasmid-mediated horizontal gene transfer and ultimately shapes the structure of the root microbiota community. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2026-07-15DOI: 10.1186/s40168-026-02469-8
Zhiying Zou, Junxiu Xi, Juan Li, Bo Lian, Cairui Fan, Haichao Cao, Weiping Liu, Shengxi Wu, Qianfa Long, Yue Hei
{"title":"Inulin alleviates vascular cognitive impairment by restoring prefrontal GABAergic function via microbiota-SCFA-GPR41/43 axis.","authors":"Zhiying Zou, Junxiu Xi, Juan Li, Bo Lian, Cairui Fan, Haichao Cao, Weiping Liu, Shengxi Wu, Qianfa Long, Yue Hei","doi":"10.1186/s40168-026-02469-8","DOIUrl":"10.1186/s40168-026-02469-8","url":null,"abstract":"<p><strong>Background: </strong>Vascular cognitive impairment (VCI) impairs medial prefrontal cortex (mPFC) function, a cognitive hub reliant on intact GABAergic transmission. Although prebiotics may counteract VCI by remodeling the gut microbiota, the underlying mechanisms remain unclear. This study investigated whether the prebiotic inulin could improve VCI by restoring mPFC GABAergic function via the gut-brain axis.</p><p><strong>Results: </strong>In a mouse model of VCI induced by bilateral carotid artery stenosis (BCAS), inulin supplementation ameliorated cognitive deficits and anxiety-like behaviors and reshaped the gut microbiota, particularly enriching SCFA-producing genera such as Ruminococcaceae. Antibiotic depletion abolished inulin's cognitive and intestinal barrier benefits, confirming microbiota dependence. In the mPFC, inulin reversed VCI-induced reductions in GABAergic synaptic transmission and GABA levels, which positively correlated with elevated colon short-chain fatty acid (SCFA) levels. Mechanistically, these effects were linked to the upregulation of SCFA receptors GPR41/43 and presynaptic restoration. Critically, shRNA-mediated knockdown of GPR41/43 abolished the behavioral and GABAergic benefits of SCFA supplementation, confirming the necessity of this signaling axis. Furthermore, to show the role of GABAergic function as inulin's final common pathway, pharmacological blockade of GABAergic signaling with bicuculline eliminated inulin's cognitive and anti-inflammatory benefits.</p><p><strong>Conclusion: </strong>Inulin alleviates VCI by elevating gut-derived SCFAs, which activate neuronal GPR41/43 in the mPFC to restore GABAergic function. These findings delineate a clear gut-mPFC pathway and support the therapeutic potential of inulin as an intervention targeting the microbiota-SCFA-GABA axis in cognitive disorders. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2026-07-10DOI: 10.1186/s40168-026-02461-2
Zhang-Chao Deng, Yu-Xuan Huang, Ke-Xin Cao, Zhe Peng, Alainaa Refaie, Mahmoud Mohamed Khalil, Ling Zhao, Le Luo Guan, Lv-Hui Sun
{"title":"Duodenal resident Limosilactobacillus improves feed efficiency through ornithine-mediated optimization of gut microbiota and nutrient absorption via the Nrf2 signaling.","authors":"Zhang-Chao Deng, Yu-Xuan Huang, Ke-Xin Cao, Zhe Peng, Alainaa Refaie, Mahmoud Mohamed Khalil, Ling Zhao, Le Luo Guan, Lv-Hui Sun","doi":"10.1186/s40168-026-02461-2","DOIUrl":"10.1186/s40168-026-02461-2","url":null,"abstract":"<p><strong>Background: </strong>The small intestinal microbiota directly influences host intestinal digestive and absorptive responses to dietary nutrients and plays a crucial role in optimizing feed efficiency in food-producing animals. However, the microbial functions of small intestine in regulating feed efficiency in broiler chickens remain to be elucidated.</p><p><strong>Methods: </strong>A total of 150 healthy broilers were individually housed under identical feeding conditions to accurately calculate their feed efficiency. The gut microbiota in different intestinal segments of high and low feed efficiency chickens were compared using 16S rRNA sequencing. Gut bacterial candidates associated with feed efficiency were identified through a two-part model, LEfSe, and the Wilcoxon rank-sum test. Another 1725 1-day-old male broiler chicks were fed either a basal diet (BD) or BD supplemented with four different bacterial candidates isolated from the chicken gut to investigate their roles in regulating gut microbiota and nutrient absorption. The underlying molecular mechanisms by which key Limosilactobacillus strains and their metabolite ornithine improve intestinal health were also examined using an intestinal epithelial cell line.</p><p><strong>Results: </strong>This study found that chickens with high feed efficiency exhibited greater microbial community stability and stronger cooperative interactions compared to low feed efficiency chickens, particularly within the duodenal microbiota. Meanwhile, duodenal resident Limosilactobacillus were significantly positively correlated with feed efficiency. Further validation trials revealed that specific Limosilactobacillus strains (L. vaginalis LD11 and L. ingluviei CC32) significantly improved feed efficiency, concurrently enhancing antioxidant capacity, barrier function, nutrient absorption, as well as increasing Limosilactobacillus abundance in the duodenum. These two bacterial strains could produce high concentrations of ornithine in the duodenum, which effectively alleviated LPS-induced intestinal cell damage by enhancing antioxidant capacity and upregulating the protein expression of nutrient transporters. Mechanistically, both bacterial strains and ornithine enhanced antioxidant capacity and nutrient uptake by activating Nrf2 signaling.</p><p><strong>Conclusions: </strong>Dietary intervention using L. vaginalis LD11 and L. ingluviei CC32 contributes to high feed efficiency by producing ornithine, which modulates the duodenal microbiota and enhances the intestinal physiological functions for nutrient absorption Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multi-omics and functional validation reveal that Methanobrevibacter-derived L-3-aminoisobutyrate alleviates subclinical mastitis in dairy goats via the HSPA1B-p65 signaling pathway.","authors":"Yu Lei, Yangbin Xu, Yiting Yan, Jinrui Zhang, Taiyuan Zhang, Jingjing Huang, Yongliang Huang, Junyu Zhong, Xiaolong Wang, Ke Zhang, Yulin Chen","doi":"10.1186/s40168-026-02464-z","DOIUrl":"10.1186/s40168-026-02464-z","url":null,"abstract":"<p><strong>Background: </strong>Subclinical mastitis (SCM) is prevalent in dairy livestock and compromises milk quality and lactation performance. Although often attributed to bacterial infection, many cases lack identifiable pathogens, suggesting alternative mechanisms. While evidence supports a gut-mammary gland axis, the microbial drivers and microbiota-derived metabolites linking gut dysbiosis to SCM remain unclear. Here, we aimed to identify SCM-associated gut microbial markers, prioritize candidate therapeutic metabolites and define the underlying mechanism.</p><p><strong>Results: </strong>Based on differences in somatic cell count (SCC) and inflammatory phenotypes across a cohort of 167 mid-lactation Saanen dairy goats, we selected 6 healthy and 6 SCM goats for downstream analyses. By integrating metagenomics, metabolomics, cross-species fecal microbiota transplantation (FMT) and functional validation in vitro and in vivo, we found that SCM was accompanied by reduced milk yield and heightened inflammatory signatures. Compared with the Healthy group, SCM goats exhibited marked remodelling of the gut microbiota, with enrichment of opportunistic taxa (Eubacterium and Blautia) and a pronounced depletion of archaeal Methanobrevibacter spp. Notably, FMT from SCM donors recapitulated mammary inflammatory phenotypes in mice, supporting a causal contribution of gut dysbiosis to mammary inflammation. Joint metagenomic functional profiling and metabolomics further identified the branched-chain amino-acid-derived metabolite L-3-aminoisobutyrate (BAIBA) as significantly enriched in the gut of healthy goats. Moreover, Methanobrevibacter spp. harboured key enzyme genes (vorA, vorB and vorD) implicated in BAIBA biosynthesis. In an LPS-challenged MAC-T model, BAIBA attenuated mammary epithelial inflammation by activating endoplasmic reticulum protein quality control programmes and restoring HSPA1B expression, thereby suppressing NF-κB activation and reducing pro-inflammatory cytokine production. Finally, in naturally infected goats, intramammary administration of BAIBA lowered SCC, highlighting translational potential.</p><p><strong>Conclusions: </strong>This study identifies BAIBA as a microbiota-derived metabolite that protects against SCM by restraining mammary inflammation via the HSPA1B-NF-κB axis, establishing a mechanistic gut-mammary link and highlighting a potential non-antibiotic intervention strategy. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}