mSystems最新文献

{"title":"Comparative transcriptional network analysis reveals ecological specialization in infant-associated species of <i>Bifidobacterium</i>.","authors":"Felipe Melis-Arcos, Masanori Arita, Daniel Garrido","doi":"10.1128/msystems.01082-26","DOIUrl":"https://doi.org/10.1128/msystems.01082-26","url":null,"abstract":"<p><p><i>Bifidobacterium</i> species are important microorganisms in the infant gut microbiota displaying substantial genomic diversity, yet how this variability is reflected in transcriptional regulatory architecture remains an open question. Here, we integrated pangenome analysis with transcription factor binding site inference and network-based approaches to compare regulatory architectures across <i>Bifidobacterium longum</i> subsp. <i>infantis</i>, <i>Bifidobacterium breve</i>, and <i>B. longum</i> subsp. <i>longum</i> using over 300 high-quality genomes. All three species exhibited open pangenomes, with regulatory interactions frequently involving accessory genes. Inferred network metrics were compared with score-randomized controls across motif-score thresholds. Increasing score stringency reduced network size while increasing the number of detected communities, indicating greater fragmentation of the retained networks rather than a measured increase in modularity. <i>NrdR</i> showed an intermediate overlap in the Clusters of Orthologous Groups (COG) category sets represented among its predicted targets and species-dependent target prevalence. HMO-related regulators (<i>FucR</i>, <i>NanR</i>, and <i>NagR</i>) differed descriptively between <i>Bifidobacterium infantis</i> and <i>B. breve</i>, the two species included in the complete three-regulator comparison, in predicted target counts, represented COG category sets, and genomic-prevalence patterns; only <i>FucR</i> showed a significant difference in accessory-target fraction. These findings identify species-dependent differences in predicted regulon composition and genomic prevalence and provide testable hypotheses about how regulatory architecture may relate to ecological specialization in the infant gut.</p><p><strong>Importance: </strong><i>Bifidobacterium</i> species are among the most abundant microorganisms in the breast-fed infant gut microbiota, where they display distinct patterns of genomic diversification and host association. However, the transcriptional regulatory mechanisms underlying these species-specific differences remain incompletely characterized. Here, we reconstructed and compared genome-scale transcriptional regulatory networks across three infant-associated <i>Bifidobacterium</i> species, integrating pangenome structure with transcription factor binding site inference across more than 300 genomes. Our analyses identified predicted regulatory interactions involving accessory genes and species-specific differences in network structure, regulon composition, and target prevalence. These associations provide hypotheses for experimental studies of how gene content and regulatory architecture may contribute to niche adaptation. This pangenome-scale framework can support the prioritization of regulatory hypotheses for future functional studies of infant-associated <i>Bifidobacterium</i>.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0108226"},"PeriodicalIF":5.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A global atlas of the gut virome reveals subtype-specific and functional alterations in irritable bowel syndrome.","authors":"Peiwei Xie, Mei Luo, Jiahui Fan, Lishou Xiong","doi":"10.1128/msystems.00901-26","DOIUrl":"https://doi.org/10.1128/msystems.00901-26","url":null,"abstract":"<p><p>The gut virome is a critical component of the microbiome-gut-brain axis; however, its role in irritable bowel syndrome (IBS) remains poorly understood due to limited sample sizes and geographic bias. We aimed to construct a comprehensive global atlas of the IBS gut virome to elucidate its composition, functional potential, and clinical relevance across diverse populations and IBS subtypes. We integrated multi-cohort data comprising 1,104 samples (790 IBS patients and 314 healthy controls) from 11 cohorts across 10 geographic regions. A standardized bioinformatic pipeline was employed to perform viral mining from metagenomic and virus-like particle-enriched metaviromic data. The IBS virome exhibited significant taxonomic alterations, with specific viral signatures distinguishing IBS-D, IBS-C, and IBS-M subtypes. Geographic region was identified as a significant factor influencing the viral community structure. Functionally, the IBS virome was enriched in auxiliary metabolic genes involved in carbon metabolism and neurotransmitter precursor synthesis (histidine and tryptophan metabolism), as well as a distinct profile of virulence factors and antibiotic resistance genes. Furthermore, in a specific cohort, certain viral taxa were significantly correlated with the severity of anxiety and depression. Machine learning models based on viral signatures achieved robust performance for IBS subtyping (area under the curve = 0.92). This study establishes a global baseline for the IBS gut virome, demonstrating that viral communities are dynamically shaped by geography and disease subtypes while encoding gene repertoires with the potential to influence host physiology, thereby providing a foundational resource for precision medicine.IMPORTANCEResearch on the human gut microbiome in IBS has focused primarily on bacteria, leaving the viral component as a vast and poorly understood reservoir. By profiling over 1,000 human samples globally, this study characterizes the taxonomic and functional features of the IBS gut virome. We demonstrate that these viral communities vary across geographic populations and IBS subtypes and are enriched in specific auxiliary metabolic genes, virulence factors, and antibiotic resistance genes. In addition, certain viral profiles show significant correlations with patient psychological symptoms such as anxiety and depression. This study also evaluates the potential of virome-based diagnostic biomarkers. Consequently, our findings provide a valuable reference for future in-depth research into the specific roles and mechanistic contributions of the gut virome in the pathogenesis of IBS.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0090126"},"PeriodicalIF":5.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Capture sequencing enables enhanced genome recovery of <i>Borrelia burgdorferi</i> in mice.","authors":"Santiago Sanchez-Vicente, Joseph Park, W Ian Lipkin, Rafal Tokarz","doi":"10.1128/msystems.01064-26","DOIUrl":"https://doi.org/10.1128/msystems.01064-26","url":null,"abstract":"<p><p>The Lyme disease spirochete, <i>Borrelia burgdorferi</i>, maintains a low burden during vertebrate infection. This limitation has historically proven to be particularly challenging for genome-based studies of <i>B. burgdorferi</i> infection and spirochete presence after antibiotic treatment. Here, we used TBDCapSeq, an oligo capture-based next- generation sequencing assay, to demonstrate its utility for genome recovery of <i>B. burgdorferi</i> directly from C3H- and BALB/c-infected mice. Tissue fragments from the ear, heart, tarsus, and infection-site skin were collected at 3 and 6 months post-tick infection from antibiotic-treated and untreated animals. We evaluated 59 tissues from 20 untreated mice and 48 tissues from 17 doxycycline-treated mice for spirochete burden and extent of genome recovery. In the untreated mice, genome recovery from each tissue was determined by the amount of borrelial DNA present in the sequencing library and was highest in the ear and heart, followed by the skin, and lowest in the tarsus. We established that approximately 50% of the genome could be recovered with as few as 10 spirochetes per assay and >90% recovery could be achieved with only 35 spirochete genomes. In the antibiotic-treated mice, trace quantities of fragmented <i>Borrelia</i> DNA were still present in tissues at 3 and 6 months. However, none of the tissue samples from these mice yielded an intact <i>B. burgdorferi</i> genome characteristic of a viable spirochete. Combined, our findings demonstrate that capture sequencing enables genomic analyses of <i>B. burgdorferi</i> directly within animal hosts.IMPORTANCELyme disease, caused by the spirochete <i>Borrelia burgdorferi</i>, is the most common tick-borne infection in the United States. Low pathogen burden is a major limitation of <i>B. burgdorferi</i> studies in animal hosts and humans that has impacted a wide range of studies ranging from diagnostics, evolutionary analyses, and pathogenesis. It has also contributed to the controversies regarding <i>B. burgdorferi</i> persistence after antibiotic treatment. We show that a next-generation capture sequencing-based approach can readily overcome the current limitations of <i>B. burgdorferi</i> genomic analyses within animal hosts. We successfully recovered abundant genomic information directly from mouse tissues, and we did not find genetic evidence of intact bacteria present after antibiotic treatment. This approach can be employed to gain further insights into <i>B. burgdorferi</i> and provide critical genome data during animal and human infection.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0106426"},"PeriodicalIF":5.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of quantitative sputum <i>Candida</i> load with respiratory dysbiosis and airway inflammation in suspected invasive pulmonary candidiasis.","authors":"Guangli Wang, Ningqing Zhang, Yanfeng Peng, Xu Wen, Xianlian Chen, Mei Zou, Song Gao, Changhang Min, Xun Min, Jian Huang","doi":"10.1128/msystems.00837-26","DOIUrl":"https://doi.org/10.1128/msystems.00837-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The clinical significance of &lt;i&gt;Candida&lt;/i&gt; species isolation from sputum remains ambiguous due to the colonization-infection dilemma. Integrating quantitative culture with microbiome profiling may clarify its role, yet systematic evidence is scarce. In this exploratory study (June 2023-June 2026), we enrolled 140 hospitalized patients suspected of invasive pulmonary candidiasis (IPC) and stratified them into possible IPC (&lt;i&gt;n&lt;/i&gt; = 36), probable IPC (&lt;i&gt;n&lt;/i&gt; = 71), and negative control (&lt;i&gt;n&lt;/i&gt; = 33) groups based on clinical criteria. All underwent quantitative fungal culture of sputum and metagenomic next-generation sequencing (mNGS). Patients were stratified by sputum &lt;i&gt;Candida&lt;/i&gt; species load into low (&lt;10&lt;sup&gt;5&lt;/sup&gt; CFU/mL), high (≥10&lt;sup&gt;5&lt;/sup&gt; CFU/mL), and negative control (0 CFU/mL) groups. We investigated associations between &lt;i&gt;Candida&lt;/i&gt; species burden, respiratory microbiota, local inflammation (IL-8), and clinical outcomes. Higher &lt;i&gt;Candida&lt;/i&gt; species load was significantly associated with prolonged hospitalization, elevated sputum IL-8, an increased microbial dysbiosis index, and depletion of key commensals (e.g., &lt;i&gt;Neisseria, Prevotella, Rothia, Streptococcus, and Veillonella&lt;/i&gt;). Counterintuitively, it correlated negatively with several classic bacterial pathogens (such as &lt;i&gt;Acinetobacter baumannii&lt;/i&gt;, &lt;i&gt;Escherichia coli&lt;/i&gt;, &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt;, &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt;, and &lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt;). A random forest model identified a nine-species microbiome signature that effectively discriminated probable from possible IPC (AUC, 0.877; 95% CI, 0.662-0.944). In patients with suspected IPC, higher sputum &lt;i&gt;Candida&lt;/i&gt; species load is associated with exacerbated respiratory dysbiosis and airway inflammation. Quantitative &lt;i&gt;Candida&lt;/i&gt; species assessment combined with microbiome signatures may serve as a complementary tool for stratifying disease severity and ecological disruption, meriting further validation in larger, multicenter cohorts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Respiratory specimens dominate clinical fungal cultures, yet interpreting the role of &lt;i&gt;Candida&lt;/i&gt; spp. in sputum remains a diagnostic dilemma. Here, by integrating quantitative culture with metagenomic sequencing, we show that a high sputum &lt;i&gt;Candida&lt;/i&gt; species load is a marker of profound ecological disruption. High &lt;i&gt;Candida&lt;/i&gt; species burden was associated with significant depletion of key commensals, an elevated dysbiosis index, and heightened local inflammation. Counterintuitively, it correlated negatively with several classic bacterial pathogens, revealing a distinct dysbiotic signature. Moreover, a microbiome-based model accurately discriminated patients with probable invasive pulmonary candidiasis. Our findings suggest that quantitative sputum &lt;i&gt;Candida&lt;/i&gt; species load, interpreted within the context of the microbial community, may be a practical biomarker for identifying patients with significant ","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0083726"},"PeriodicalIF":5.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics elucidate octapeptin mechanisms in alleviating intestinal injury in mice challenged with ETEC K88 via modulated microbial and host pathways.","authors":"Jianfei Zhao, Zhongqian Lu, Qiuyang Liu, Jingbo Liu, Li Wang, Jinxiu Huang, Feiyun Yang, Haitao Yu","doi":"10.1128/msystems.01032-26","DOIUrl":"https://doi.org/10.1128/msystems.01032-26","url":null,"abstract":"<p><p>The mechanisms whereby antimicrobial peptides (AMPs) confer intestinal protection during enteric bacterial infection remain unclear. Here, we examined the protective effects and underlying mechanisms of the AMP, octapeptin, against intestinal infection induced by enterotoxigenic <i>Escherichia coli</i> K88 (ETEC K88) in mice. Octapeptin ameliorated intestinal injury by modulating gut microbiome-host interactions. When compared with ETEC K88 mice, octapeptin significantly attenuated growth retardation, systemic oxidative stress, pro-inflammatory cytokine elevation, and ileal morphological damage. Integrated cecal microbiome, metabolome, and ileal transcriptome analyses revealed that octapeptin reversed ETEC K88-induced dysbiosis, notably increasing beneficial genera abundance. Concomitantly, octapeptin altered microbial metabolite profiles and significantly influenced ileal gene expression in circadian rhythm regulation. Correlation analysis and variance partitioning further identified a coherent \"microbiota-metabolite-transcriptome\" axis underlying these phenotypic improvements. Thus, octapeptin alleviates ETEC K88-induced intestinal injury via multi-level interactions that restore microbial ecology and regulate host circadian and immune pathways, thereby highlighting host-directed AMP mechanisms.IMPORTANCEAntimicrobial peptides are promising alternatives to antibiotics, but how they work inside the body remains poorly understood. Using a multi-omics approach, this study shows that octapeptin, a natural cyclic lipopeptide, protects mice against intestinal infection by reshaping the gut microbiota, reprogramming gut metabolites, and stabilizing host circadian clock genes that are disrupted by infection. These findings reveal a previously unrecognized link between gut microbes and the intestinal circadian clock. This mechanistic framework could guide the development of peptide-based strategies to prevent enteric infections in animals.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0103226"},"PeriodicalIF":5.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative performance of reference-based metagenomic tools to identify species-level taxa among families of bacteria: benchmarking <i>Mycobacteriaceae</i> and <i>Neisseriaceae</i>.","authors":"Luke B Harrison, Juba O Ahmed, Gnéré M Coulibaly, Frédéric J Veyrier","doi":"10.1128/msystems.00444-26","DOIUrl":"https://doi.org/10.1128/msystems.00444-26","url":null,"abstract":"<p><p>Hypotheses concerning the ecology and evolution of bacteria commonly relate to the presence and abundance of species in various settings and conditions. Shotgun metagenomics may address these hypotheses, which previously relied on PCR or culture. However, the problem of determining the presence/absence of a given species of interest is not trivial, particularly when closely related species are present in the reference database or metagenomic sample. Reference-based methods for detecting species-level taxa mostly rely on thresholding of aligned reads or mapped k-mers, or derivative metrics such as genomic coverage, creating a trade-off between recall/completeness and precision/purity. New methods for species-level profiling (YACHT, Metapresence, and sylph) have recently been published. Here, we test the performance of these methods, along with Kraken2/bracken and MetaPhlAn4, to detect related species of interest using simulated metagenomic samples from genomes in the families <i>Mycobacteriaceae</i> and <i>Neisseriaceae</i>, which contain closely related genomes. Among methods tested, Metapresence, when used with an alignment quality filter, and sylph offer the best overall performance. Sylph maintains high precision but requires a depth of coverage greater than approximately 0.1× to reliably detect a genome's presence. Metapresence has a lower limit of detection of hundreds of reads, but this is balanced against relatively lower precision. Both methods are relatively robust to the presence of reads from genomes outside the groups of interest. We demonstrate the application of these methods in two real-world data sets: a mycobacterial community in a drinking water system and the community of <i>Neisseriaceae</i> present in the human oral cavity.</p><p><strong>Importance: </strong>Detecting which bacterial species of interest are present in a given sample is fundamental to studies of microbial ecology and evolution and to applied microbiology (e.g., clinical diagnostics). Culture-dependent and culture-independent (e.g., PCR) approaches are increasingly complemented by metagenomic approaches, but methods to accurately identify specific low-abundance species-level genomes in a shotgun metagenomic sample are still being refined. Here, we comprehensively test YACHT, Kraken2/bracken, Metapresence, MetaPhlAn4, and sylph using two simulated data sets of bacterial families, <i>Mycobacteriaceae</i> and <i>Neisseriaceae</i>, that contain closely related species. Our simulations exploit natural genomic diversity to create a challenging benchmark. We demonstrate that Metapresence and sylph perform best, with the former being well suited to low-biomass host-associated data sets and the latter with environmental metagenomic samples. This study is the first extensive benchmark of these methods for this use case and demonstrates that these methods can accurately identify closely related species of interest.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0044426"},"PeriodicalIF":5.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated multi-omics and metabolic modeling links structure to function in high-performing electrosynthetic biofilm communities.","authors":"Rozanne Stroek, Minke Gabriëls, Marijn Winkelhorst, Marcel van den Broek, Martin Pabst, Ludovic Jourdin, Jean-Marc Daran, Djordje Bajic","doi":"10.1128/msystems.00803-26","DOIUrl":"https://doi.org/10.1128/msystems.00803-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Microbial electrosynthesis (MES) is a promising technology for the valorization of CO&lt;sub&gt;2&lt;/sub&gt; into industrially relevant building blocks. The high-performing MES systems in terms of production rates of acetate (12.5-19.7 mmol L&lt;sup&gt;-1&lt;/sup&gt;&lt;sub&gt;catholyte&lt;/sub&gt; day&lt;sup&gt;-1&lt;/sup&gt;), butyrate (1.9-12.2 mmol L&lt;sup&gt;-1&lt;/sup&gt;&lt;sub&gt;catholyte&lt;/sub&gt; day&lt;sup&gt;-1&lt;/sup&gt;), and caproate (0.6-0.9 mmol L&lt;sup&gt;-1&lt;/sup&gt;&lt;sub&gt;catholyte&lt;/sub&gt; day&lt;sup&gt;-1&lt;/sup&gt;) discussed in this study consist of mixed microbial communities. However, the microbial community members, metabolic pathways, and interactions driving product formation in MES communities remain poorly understood. To overcome these challenges, we conducted a comprehensive characterization of three high-performing MES communities, combining multi-omics with metagenome-scale metabolic modeling. Using a high-resolution metagenomic pipeline, we reconstructed high-quality genomes of 25 metagenome-assembled genomes present in our reactors, including six fully circular genomes. We report the presence of &lt;i&gt;Clostridium aromativorans&lt;/i&gt; for the first time in a gas-fermenting system. In particular, our findings identified three acetogenic species, &lt;i&gt;Eubacterium limosum&lt;/i&gt;, &lt;i&gt;Sporomusa sphaeroides&lt;/i&gt;, and &lt;i&gt;C. aromativorans&lt;/i&gt;, as key contributors to the production of acetate, butyrate, and caproate via the Wood-Ljungdahl and the reverse β-oxidation pathways. In addition, we found genes related to lactate and ethanol production from acetyl-CoA, along with proteomic evidence of lactate production. This paves the way for investigating the role of cross-fed metabolites such as lactate and ethanol as electron donors in chain elongation. Finally, meta-genome-scale metabolic modeling suggests that the communities might be sustained by the cross-feeding of specific cofactors such as pyridoxine, pantothenate, biotin, and thiamin. This study provides key insights into the structure and function of electrosynthetic communities, bringing us closer to the rational engineering of MES systems.IMPORTANCEMicrobial electrosynthesis (MES) offers a promising route to transform CO&lt;sub&gt;2&lt;/sub&gt; and renewable electricity into valuable platform chemicals. However, the microbial ecology governing the assembly and function of these systems remains poorly understood, limiting our ability to engineer them. By integrating high-resolution multi-omics with metabolic modeling, this study provides a systems-level framework to dissect the structure and function of electrosynthetic microbial communities. Understanding which organisms drive carbon fixation and chain elongation, how electrons and intermediates are transferred within the biofilm, and how metabolic dependencies structure these communities is essential for improving productivity and product specificity in MES. More broadly, this work highlights how integrated multi-omics approaches can resolve the functional organization of complex microbial ecosystems and provides methodological adv","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0080326"},"PeriodicalIF":5.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota-derived indole-3-propionic acid preserves dorsal hippocampal catecholamines to prevent post-stroke cognitive impairment.","authors":"Yisi Liu, Huaying Zhang, Fangbo Xia, Xuxuan Gao, Fan Wu, Xin Zhao, Mengxi Li, Yanni Zheng, Siqi Yan, Kaiyu Xu, Muxuan Chen, Yueran Ren, Weike Hu, Zhuang Li, Jia Yin, Hongwei Zhou, Dongxin Zhang","doi":"10.1128/msystems.00907-26","DOIUrl":"https://doi.org/10.1128/msystems.00907-26","url":null,"abstract":"<p><p>Gut dysbiosis has been increasingly implicated in post-stroke cognitive impairment (PSCI); however, the causal contribution and therapeutic potential of gut microbiota-derived metabolites remain unclear. This study aimed to identify key microbiota-derived metabolites involved in PSCI and elucidate their underlying mechanisms. We found that both PSCI patients and middle cerebral artery occlusion (MCAO) mice exhibited distinct gut microbial alterations, characterized by a marked reduction in tryptophan-metabolizing bacteria and indole-3-propionic acid (IPA), a gut microbiota-derived tryptophan metabolite. Exogenous IPA administration alleviated PSCI-like phenotypes in MCAO mice. Mechanistically, IPA preserved tyrosine hydroxylase-positive (Th⁺) fibers and catecholamine levels in the dorsal hippocampus. Further analyses showed that IPA binds to the adaptor protein Ywhab, promotes ERK activation, and enhances neuronal survival, thereby counteracting neuronal apoptosis-associated inflammation, and subsequent Th⁺ fiber degeneration. These findings identify IPA as a gut microbiota-derived neuromodulator that mitigates PSCI by preserving dorsal hippocampal catecholaminergic transmission. IPA may therefore serve as a therapeutic candidate for PSCI.</p><p><strong>Importance: </strong>The advance of the present work lies in defining a mechanistic link between microbiota-derived IPA deficiency and post-stroke cognitive dysfunction rather than acute ischemic injury alone. We show that circulating IPA is persistently reduced in patients who develop PSCI and in MCAO mice and that early IPA supplementation improves post-stroke memory by preserving dorsal hippocampal TH-positive fibers and catecholamine availability. Mechanistically, we identify Ywhab as an IPA-binding protein and demonstrate that modulation of the Ywhab-ERK pathway promotes neuronal survival, limits secondary neuroinflammation, and preserves catecholaminergic projections. Importantly, Ywhab knockdown reproduced several protective effects of IPA, including reduced neuronal apoptosis and microglial activation, preservation of TH-positive fibers, and improved cognitive performance. These findings nominate Ywhab as a potential therapeutic target for PSCI and distinguish the present study from previous reports describing only the general neuroprotective effects of IPA.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0090726"},"PeriodicalIF":5.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Escherichia coli</i>-derived enterobactin is associated with delayed gut microbiome maturation in infants born to mothers with obesity.","authors":"Artur Kovenskiy, Nurislam Mukhanbetzhanov, Zharkyn Jarmukhanov, Arailym Duisebayeva, Marina Morenko, Alibek Kossumov, Laura Chulenbayeva, Elizaveta Vinogradova, Maxim Popov, Almagul Kushugulova, Samat Kozhakmetov","doi":"10.1128/msystems.00986-26","DOIUrl":"https://doi.org/10.1128/msystems.00986-26","url":null,"abstract":"<p><p>Maternal obesity has been increasingly recognized as a factor influencing early-life microbiome development. However, its impact on the infant gut resistome and virulome remains insufficiently characterized. In this prospective longitudinal study, we investigated gut microbiome composition, antibiotic resistance genes (ARGs), and virulence factor profiles in infants born to mothers with obesity and normal weight during the first year of life. Shotgun metagenomic sequencing was performed on maternal and infant fecal samples collected at birth and at 1, 3, 6, and 12 months. Infants born to obese mothers exhibited delayed microbiome maturation characterized by early enrichment of Pseudomonadota, particularly <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>, and reduced abundance of <i>Bifidobacterium</i> species. This compositional pattern was accompanied by a significantly higher ARG burden in early life, including enrichment of genes associated with antibiotic inactivation, efflux mechanisms, and β-lactam resistance. Although taxonomic differences between groups were no longer statistically detectable at the 12-month time point, where the sample size was smallest, functional disparities in the resistome persisted. Additionally, infants born to obese mothers demonstrated increased relative abundance of secretory virulence-associated genes and <i>E. coli</i>-derived enterobactin, suggesting enhanced iron-scavenging capacity and competitive potential of Enterobacteriaceae. Together, these findings suggest that maternal obesity is associated with altered early microbial ecological dynamics, promotes resistome expansion, and may delay transition toward a stable Bacteroidota- and Bacillota-dominated microbiome.IMPORTANCEThe first year of life is a critical window for gut microbiome development, during which early microbial disturbances may influence later health. This study shows that maternal obesity is associated not only with altered infant microbial succession but also with functional changes in the infant gut microbiome, including greater antibiotic resistance gene burden and enrichment of virulence-associated traits. The finding of increased <i>Escherichia coli</i>-derived enterobactin suggests that iron-scavenging mechanisms may help Enterobacteriaceae persist during early infancy and may contribute to delayed microbial maturation. By linking maternal obesity with infant microbiome development, resistome expansion, and virulence-related functions, this work provides new insight into how maternal metabolic status may shape early microbial ecology and potential microbiome-associated risks.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0098626"},"PeriodicalIF":5.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of IgA-Seq in schizophrenia to identify key gut bacteria that promote abnormal behavior in mice.","authors":"Caihong Liu, Huixiong Chen, Xing Wan, Chunming Zhong, Ruibin Luo, Litao Yang, Yinmei Wang, Haiyan Cui, Cheng Jiang, Mingbang Wang, Chen-Zhong Li, Ruihuan Xu","doi":"10.1128/msystems.00786-26","DOIUrl":"https://doi.org/10.1128/msystems.00786-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Schizophrenia (SCZ) has a complex etiology, and growing evidence implicates the microbiota-gut-brain axis. Because abundance-based profiling does not identify taxa closely engaged by mucosal immunity, we used immunoglobulin A (IgA)-based bacterial sorting to prioritize candidate SCZ-associated gut bacteria and evaluated cultured consortia in mouse models. Fecal samples were collected from participants with SCZ, other mental disorders, and healthy controls, which underwent 16S rRNA gene sequencing before and after magnetic separation of IgA-coated (IgA+) and non-IgA-coated (IgA-) bacteria. Taxa prioritized by the IgA coating index were anaerobically cultured, pooled into defined IgA+ and IgA- consortia, and administered to germ-free (GF) C57BL/6J, antibiotic-pretreated &lt;i&gt;Rag1&lt;/i&gt;&lt;sup&gt;-/-&lt;/sup&gt; SPF, and conventional SPF C57BL/6J mice. In the bacterial treatment groups, MK-801 was introduced only during the final 7 days of consortium gavage; the GF NaCl control received intraperitoneal saline during the corresponding final 7-day period. Behavioral, serological, colonic, and hippocampal outcomes were assessed according to the endpoints specified for each experiment. Candidate IgA+ taxa included &lt;i&gt;Streptococcus&lt;/i&gt;, &lt;i&gt;Pseudomonas&lt;/i&gt;, and &lt;i&gt;Parabacteroides&lt;/i&gt;, whereas IgA- candidates included &lt;i&gt;Collinsella&lt;/i&gt;, &lt;i&gt;Eggerthella&lt;/i&gt;, &lt;i&gt;Bifidobacterium&lt;/i&gt;, &lt;i&gt;Bacteroides&lt;/i&gt;, &lt;i&gt;Enterococcus&lt;/i&gt;, and &lt;i&gt;Clostridium&lt;/i&gt;. In experiment 1, the GF IgA+ and GF IgA- groups differed in open-field center-zone time (&lt;i&gt;P&lt;/i&gt; = 0.032). Marble-burying behavior showed a significant overall difference among the five groups (&lt;i&gt;P&lt;/i&gt; = 0.040), with a significant pairwise difference between GF IgA+ and GF IgA- mice (&lt;i&gt;P&lt;/i&gt; = 0.022). Y-maze spontaneous alternation showed no overall group difference (&lt;i&gt;P&lt;/i&gt; = 0.81). Forced-swim immobility showed a significant overall group effect (&lt;i&gt;P&lt;/i&gt; = 0.020), with significant pairwise differences between GF IgA+ and GF IgA- mice (&lt;i&gt;P&lt;/i&gt; = 0.020) and between GF IgA- and &lt;i&gt;Rag1&lt;/i&gt;&lt;sup&gt;-/-&lt;/sup&gt; IgA- mice (&lt;i&gt;P&lt;/i&gt; = 0.030). IL-6 was frequently undetectable and was not compared statistically; TNF-α showed a significant overall analysis of variance group effect (&lt;i&gt;P&lt;/i&gt; = 0.040), but no Tukey-adjusted pairwise comparison was significant. Colon length also showed a significant overall group effect (&lt;i&gt;P&lt;/i&gt; = 0.010), with shorter colons in the GF IgA+ group than in the GF saline and GF IgA- groups (both pairwise &lt;i&gt;P&lt;/i&gt; = 0.016), although colonic histology was largely normal. Descriptive hippocampal alterations were observed in GF IgA+ consortium mice. In conventional specific pathogen-free mice, MK-801 was introduced after the first 7 days of consortium gavage and continued during the final 7 days; under this exposure schedule, the IgA+ consortium was associated with greater colonic mucosal injury than the IgA- consortium. IgA-based prioritization identified candidate SCZ-associated taxa, and the resulting conso","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0078626"},"PeriodicalIF":5.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}