mSystems最新文献

{"title":"Multi-kingdom gut microbiota analyses identify biomarkers of different types of pediatric short bowel syndrome.","authors":"Qing-Qing Wu, Cheng-Yong Li, Shan-Shan Chen, Juan Xu, Wei-Hui Yan, Li-Na Lu, Hai-Xia Feng, Jin-An Zhou, Lu Wang, Ning-Ning Liu, Lu Jiang, Ying Wang","doi":"10.1128/msystems.00316-26","DOIUrl":"10.1128/msystems.00316-26","url":null,"abstract":"<p><p>Despite recent advances in bacterial profiling across the three anatomical types of pediatric short bowel syndrome (SBS), the gut multi-kingdom remains unexplored. We characterized the four-kingdom gut microbiota using modified DNA extraction and deep shotgun metagenomic sequencing of fecal samples from 26 healthy controls and 34 pediatric SBS patients comprising three types (8 SBS I, 15 SBS II, and 11 SBS III). Overall, children with SBS exhibited a significant reduction in α-diversity compared with controls, with no difference observed among SBS types. Compared with controls, the proportion of archaea was significantly decreased in all SBS types, while bacteria, fungi, and viruses remained similar across types. Different types of SBS exhibited distinct microbial signatures: SBS I was enriched with pathogens (such as species from the <i>Streptococcus</i> and <i>Klebsiella</i> genera); SBS II was marked by a depletion of beneficial short-chain fatty acid-producing species (such as <i>Faecalibacterium prausnitzii</i>); and SBS III displayed loss of bile acid-metabolizing species, alongside a significant expansion of <i>Lactobacillus</i> species. Ecological networks were rewired in SBS, with disruption pronounced in SBS I. Functional analysis revealed that core metabolic pathways were markedly suppressed in SBS I compared with controls. Integrated correlation analyses revealed ileocecal valve loss as the primary determinant of SBS I microbial profiles, linking it to impaired secretory functions and hepatic injury. Our findings deciphered type-specific alterations in the multi-kingdom microbiota and their functional profiles, providing the basis for designing precision microbial therapies aimed at improving long-term outcomes for children with SBS.IMPORTANCEPediatric short bowel syndrome (SBS) is a primary cause of intestinal failure, yet prior research characterizing the gut microbiota has focused almost exclusively on bacteria. In this study, we characterized the multi-kingdom microbiome (including bacteria, fungi, archaea, and viruses) across the three anatomical types of pediatric SBS. We found that different SBS subtypes showed distinct microbial patterns: SBS I was enriched in pathogens, SBS II exhibited a depletion of beneficial short-chain fatty acid-producing species, and SBS III was characterized by a loss of bile acid-metabolizing microbes with an expansion of <i>Lactobacillus</i>. Functional analysis showed that SBS I had markedly suppressed core metabolic pathways, and integrated analyses identified the ileocecal valve as a key determinant of microbial gene profiles, with its loss linked to impaired secretion and liver injury. These findings provide a comprehensive multi-kingdom view of the pediatric SBS microbiome and highlight anatomical determinants shaping host-microbiome dysfunction.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0031626"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The quantitative amino acid economy of yeast reveals public versus private goods and guides syntrophic community design.","authors":"Shabbir Ahmad, Ganesh Muthu, Sunil Laxman","doi":"10.1128/msystems.00333-26","DOIUrl":"10.1128/msystems.00333-26","url":null,"abstract":"<p><p>The biosynthetic capacity of a cell governs the production and exchange of amino acids. Given the distinct metabolic origins and intracellular requirements for amino acids, it is essential to establish quantitative amounts of internal amino acid pools and how these change across growth phases. Using <i>Saccharomyces cerevisiae</i>, here we establish an absolute, quantitative blueprint of the intracellular and extracellular amino acid economy, defining the fluxes of production, secretion, and consumption across 24 hours of cell growth. While the intracellular pool is dominated by a group of amino acids, their relative proportions continuously change over time. The extracellular pool is notably distinct in terms of composition and amounts. Only select amino acids are public goods secreted in significant amounts, and a subset of these (Ala, Val, Gln, Trp, and Phe) are subsequently re-consumed. Five amino acids, Asp, Lys, His, Arg, and Met, remain \"privatized\" even in nutrient abundance. We demonstrate that the strictly privatized amino acid Asp continuously sustains diverse carbon metabolism, while the public Ala is utilized following carbon depletion. Furthermore, nitrogen limitation triggers a significant shift toward storage, privatizing otherwise abundant nitrogen-rich compounds like Gln, Asn, and Pro. We thereby rationally establish pairs of stable synthetic communities of paired public good auxotrophs that show effective growth. Our results identify frameworks for feasible amino acid trade and provide a basis for engineering stable, synthetic communities of amino acid auxotrophs.IMPORTANCEAmino acids are central to a metabolic economy and are extensively exchanged between cells; yet, the scale of this economy remains unknown even in model microbes. This study establishes a quantitative blueprint of the amino acid economy in <i>Saccharomyces cerevisiae</i> by mapping production, secretion, and consumption fluxes. The findings reveal a distinction between public goods-such as alanine, which is secreted and re-consumed-and privatized resources, such as aspartate, which cells retain to sustain carbon metabolism. These pools shift across growth phases and move toward privatization during nitrogen limitation. By defining these frameworks, this study enables the rational design of stable, synthetic communities of auxotrophs.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0033326"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ancestral hydrocarbon metabolism enables PET degradation by a natural bacterial consortium.","authors":"Sabrina Edwards, Danny Rice, Patricio Palomino, Irene Newton, Jay L Mellies","doi":"10.1128/msystems.00829-26","DOIUrl":"10.1128/msystems.00829-26","url":null,"abstract":"<p><p>Plastic biodegradation in natural environments is increasingly recognized as a multi-organism process; however, the mechanisms enabling coordinated depolymerization and metabolism of polyethylene terephthalate (PET) remain poorly understood. Previously, we demonstrated that a full consortium containing three <i>Pseudomonas</i> and two <i>Bacillus</i> strains isolated from hydrocarbon-rich coastal soils of Galveston Bay, Texas, can synergistically depolymerize PET plastic and utilize it as a sole carbon source, a capacity not observed in individual isolates. In this report, using integrated comparative genomics, proteomics, and chemical analyses, we show that PET degradation in this system reflects exaptation of hydrocarbon metabolism, reinforced by metabolic division of labor. Within this naturally occurring consortium, <i>Bacillus</i> strains persist under environmental stress, establish biofilms, and perform essential secondary hydrolysis, while <i>Pseudomonas</i> strains catabolize aromatic monomers and buffer oxidative stress. Genes supporting these functions are enriched within the accessory genomes of the consortium strains, indicating consortium-enriched horizontal gene transfer. In addition to the canonical two-step hydrolytic pathway well documented in PET biodegradation, we identify a secondary methylation- and redox-associated process, mechanisms where the full consortium acts on the oligomer mono(2-hydroxyethyl) terephthalate (MHET), yielding nearly complete conversion to terephthalic acid and methylated MHET. Together, these findings support a model in which PET degradation is driven by pre-existing hydrocarbon metabolic traits distributed across the native consortium, particularly stress-response and redox pathways, aromatic catabolism, and alcohol catabolism.</p><p><strong>Importance: </strong>Environmental plastic degradation is rarely accomplished by a single organism; however, the microbial mechanisms enabling community-level polyethylene terephthalate (PET) plastic breakdown remain poorly understood. This study shows that a bacterial consortium isolated from crude petroleum-contaminated coastal soils degrades PET by coordinating older hydrocarbon, aromatic, stress-response, and redox-associated metabolisms rather than by acquiring a dedicated PET pathway. Predicted horizontal gene transfer events were linked mainly to survival, biofilm formation, and metabolic flexibility, not PET depolymerization itself. These findings shift the focus from searching for single PET-degrading organisms toward understanding how microbial communities combine pre-existing metabolic tools to process synthetic polymers and manage the chemical stress created during biodegradation.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0082926"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Within-host population structure, migration, and parallel adaptive evolution of <i>Pseudomonas aeruginosa</i> in cystic fibrosis lung disease.","authors":"David Ritz, Michelle E Clay, Ted Kim, Rachel D Van Gelder, Jayadevi H Chandrashekhar, Alan J Collins, Alix Ashare, Jay Goddard, Kenneth B Hoehn, Daniel Schultz, Rachel J Whitaker, Deborah A Hogan","doi":"10.1128/msystems.00238-26","DOIUrl":"10.1128/msystems.00238-26","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> infections in adults with cystic fibrosis (CF) are comprised of heterogeneous populations, most often tracing ancestry back to a single recent common ancestor. What is not clear is the physical spatial structure within the lung infection population, its stability over time, and whether this physical structure leads to different evolutionary trajectories in different adaptive environments. To compare the <i>P. aeruginosa</i> populations across a single lung, we performed whole genome sequence analyses of 450 isolates recovered from lavage samples of the three different lobes of the right lung from a person with mild-to-moderate CF lung disease at three time points over the course of ~1.5 years. We found that isolates fell into five distinct phylogenetic lineages with evidence for repeated translocation of isolates from different lineages across lobes and loss-of-function mutations in <i>lasR</i> and <i>mucA</i> were present in all 450 isolates. The well-resolved phylogenetic analyses revealed a structured population in which we find the coexistence of a slowly evolving lineage and more rapidly evolving lineages. There is also support for numerous migration events. Furthermore, strong evidence for parallel adaptive mutations in multiple genes revealed distinct evolutionary paths affecting mucoid phenotypes and genetic variation in antibiotic resistance-associated pathways across coexisting populations within a single individual over time. These results provide an example of within-host evolution leading to microheterogeneity that may be useful to consider in future study of infection metapopulations dynamics over the course of chronic infection.IMPORTANCEIndividuals with cystic fibrosis (CF) commonly have chronic lung infections that contain clonally derived <i>Pseudomonas aeruginosa</i> populations with genotypic and phenotypic diversity. This study describes a substantial data set containing 450 isolates from different lobes of the right lung across three time points from an individual with mild-to-moderate CF lung disease. Some regional enrichment for specific lineages with parallel mutations among individual lobes of the lung was observed, but longitudinal analysis also demonstrated that compartmentalization is not strictly maintained and that isolates migrate between lobes of the lung over time. Perspectives on within lung evolution will be important for understanding the pathogen populations in chronic respiratory infections in CF and other diseases.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0023826"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-adjusted machine learning identifies facial skin microbes associated with skin quality among Korean women.","authors":"Sangbeen Park, Hye-Been Kim, Hyunsoo Ahn, Geunyeong Lee, Woomin Song, Misun Kim, Eunjin Park, Byung Sun Yu, Miyang Han, Seyoung Mun, Dong-Geol Lee, Chun Ho Park, Seunghyun Kang, HyungWoo Jo, Sanguk Kim","doi":"10.1128/msystems.00840-26","DOIUrl":"10.1128/msystems.00840-26","url":null,"abstract":"<p><p>Recognizing specific microbes that significantly influence skin quality is becoming an essential aspect of personalized skincare. However, conventional large-scale cohort skin microbiome studies often overlook important confounders, such as age, leading to missing meaningful microbe-skin relationships. In this study, we developed an age-adjusted machine learning (AAML) framework to identify microbial candidates associated with skin quality by determining optimal age ranges that enhance age-independent signals of skin microbes. It allowed the identification of distinct age groups that clearly explain specific skin microbial effects, as well as potential microbes showing notable age-independent links to skin quality, which were not observed in analyses across the entire age spectrum. In particular, <i>Corynebacterium propinquum</i> (<i>C. propinquum</i>) was recognized as a key species that positively impacts the middle-aged group, especially regarding skin tone. We further validated its dermatological significance using functional assays in human skin cell lines, performed a gene-level functional analysis, and suggested a potential mechanism. Our AAML method can be adapted to other microbiome analyses to precisely measure factors unaffected by age-related confounding factors.IMPORTANCEAge is a crucial but often intractable confounder in microbiome studies, obscuring how specific microbes affect human traits. We developed an age-adjusted machine learning (AAML) framework that automatically finds age ranges where the microbiome best predicts skin quality, rather than relying on arbitrary age groups. In a Korean facial skin cohort, AAML revealed three biologically meaningful age windows and uncovered microbial effects that are invisible in whole-age analyses. AAML identified <i>Corynebacterium propinquum</i> as a previously unrecognized commensal microbe that improves skin tone in the middle-aged group, and we mechanistically linked this effect to resveratrol production. Our framework provides a general, confounder-aware strategy for discovering age-independent microbiome-host relationships.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0084026"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing anti-phage defenses to differentially arrest the viral lifecycle reveals the regulatory logic of a parasitic satellite.","authors":"S Tansu Bagdatli, Kimberley D Seed","doi":"10.1128/msystems.00428-26","DOIUrl":"10.1128/msystems.00428-26","url":null,"abstract":"<p><p>Mobile genetic elements frequently encode defense mechanisms to protect their bacterial hosts from viral attack. In <i>Vibrio cholerae</i>, these defensive elements include phage-inducible chromosomal island-like elements (PLEs), which are phage satellites that act as highly specialized parasites of the lytic phage ICP1. While PLE transcriptional activation upon ICP1 infection is known to be temporally regulated, the underlying regulatory logic and dependencies on the progression of the phage's developmental program required for activation remain unclear. In this study, we took a novel approach to define these dependencies by introducing independent anti-phage defense systems, BREX and DarTG, as molecular roadblocks to impede the ICP1 lifecycle. We discovered that, for both ICP1 and PLE, late-stage gene expression is fundamentally uncoupled from genome replication, representing a striking departure from the standard paradigm for double-stranded DNA phages. While BREX restricts ICP1 to an immediate-early transcriptional state that stalls PLE activation, DarTG allows the phage to execute its full transcriptional cascade despite the total block in DNA replication. This permissive environment provides the necessary cue(s) for complete PLE induction, revealing that robust PLE activation is profoundly dependent on the transcriptional progression of its helper phage.IMPORTANCEBacteria and their viruses (phages) are locked in perpetual evolutionary conflict. Some bacteria harbor phage satellites, specialized parasites that are activated to hijack the phage's components to spread all the while inhibiting viral production. While some satellites respond to a single viral trigger, the regulation of many satellites, including clinically relevant phage-inducible chromosomal island-like elements (PLEs) in <i>Vibrio cholerae</i>, remains poorly understood. Here, we used bacterial defense systems as molecular roadblocks to probe how PLE activation depends on its helper phage. We found that severe disruptions to viral transcription stall PLE activation. Unexpectedly, both the virus and the satellite can execute their full transcriptional programs even when DNA replication is completely blocked, challenging a fundamental paradigm in virology. These insights reveal a sophisticated level of phage-satellite coordination, illustrating how satellite activation is tightly linked to the transcriptional state of its helper phage, a dependency that ultimately drives the dissemination of mobile genetic elements.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0042826"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking evolutionary inference in metagenomic time series.","authors":"Alexander Eiler","doi":"10.1128/msystems.00693-26","DOIUrl":"10.1128/msystems.00693-26","url":null,"abstract":"<p><p>As ecologists increasingly use metagenomic time series to track evolution in the wild, there is a risk of misinterpreting ecological dynamics as rapid adaptation. This Perspective identifies methodological limitations that generate misleading signatures of microbial evolution. A primary issue is confusing evolutionary change (driven by <i>de novo</i> mutation or horizontal gene transfer) with ecological lineage turnover, such as seasonal oscillations or the reactivation of dormant lineages. Current metagenome-assembled genomes can collapse micro-diverse lineages and decouple adaptive mobile elements, creating inaccurate genomic signatures of sweeps or stasis. To address these issues, I propose a framework integrating long-read sequencing, pangenome graph theory, and forward-time simulations to model populations as temporal genetic networks and better resolve microbial evolutionary dynamics.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0069326"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virome DNA stable isotope probing reveals diverse active soil virus communities across ecosystem contexts.","authors":"Ernest D Osburn, Minjae Kim","doi":"10.1128/msystems.00733-26","DOIUrl":"10.1128/msystems.00733-26","url":null,"abstract":"<p><p>Viruses are increasingly recognized as important players in soil ecosystems, but the active lytic virus populations that influence microbe-mediated terrestrial ecosystem processes remain mostly uncharacterized. Here, we trace ¹³C-labeled glucose from host microorganisms into virus genomic DNA to identify virus populations actively involved in soil carbon (C) cycling, i.e., viruses that lysed ¹³C-incorporating microbes. We present experimental evidence of isotope labeling (i.e., lytic activity) of more than 5,000 virus populations. The active viruses lysed hosts from 197 microbial families across 28 prokaryotic phyla. Viral lysis was greater in C-limited agricultural soils compared with C-rich forest soils, highlighting C availability/inputs as key factors that mediate virus life cycles. Active viruses disproportionately lysed microorganisms in the Bacillota, Bacteroidota, and Pseudomonadota phyla, likely reflecting glucose-induced growth responses of microbial copiotrophs within those groups. Supporting this, we observed that the degree of virus genome isotope labeling was positively correlated with the growth potential of the microbial hosts. Furthermore, the active viruses exhibited unique genomic characteristics compared to the inactive viruses, including a greater prevalence of lysogeny-associated genes and distinct profiles of putative auxiliary metabolism genes in the active virus genomes. Overall, our results demonstrate a link between microbial growth traits and virus activity and suggest that substrate-induced viral lysis significantly influences microbial population turnover in soil. Our results also show that virus activity in response to C inputs is highly variable among soil contexts, with implications for the varying ecosystem-scale influences of viruses among terrestrial environments.IMPORTANCEIn this study, we used a new method of detecting active viruses that lyse (kill) their microorganism hosts in soil. We accomplished this by tracing \"heavy\" versions of carbon from soil microorganisms into the DNA of their virus parasites. This showed that there are thousands of different potentially active virus populations in soil and that the microorganisms that get lysed the most are those that grow the fastest. However, the activity of viruses was very high in some ecosystems (agricultural soils) and much lower in others (forest soils). Our results show that viruses can play an important role in influencing soil microbial communities, but that the size of their effects is very different in different types of ecosystems. Our study also describes a new method that can be extended to further explore the roles and importance of viruses across different environmental conditions and different ecosystem types.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0073326"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel insights into <i>Radix Pseudostellariae</i> saponins assist <i>Mycoplasma gallisepticum</i> attenuated vaccine to enhance the immunoprotection of chicken.","authors":"Qixian Feng, Lihua Liao, Yihua Gong, Jingru Xu, Xiangduan Wei, Zhengrun Xiao, Pengqiang Chen, Beilei Chen, Kaizhao Zhang, Quanxi Wang","doi":"10.1128/msystems.00781-26","DOIUrl":"10.1128/msystems.00781-26","url":null,"abstract":"<p><p><i>Mycoplasma gallisepticum</i> (MG) is a major pathogen causing chronic respiratory disease in chickens, and the MG-attenuated vaccine (MGAV) often fails to induce effective mucosal immunity. <i>Radix Pseudostellariae</i> saponins (RPS), important bioactive components of the traditional Chinese herb, have been utilized for immunomodulation, although the underlying mechanisms remain to be elucidated. In this study, chickens were randomly assigned to groups receiving intranasal MGAV alone, MGAV plus RPS at different doses, or appropriate controls. Serum, tracheal mucosa, and respiratory lavage samples were collected for antibody measurement, cytokine profiling, histological assessment, and metagenomic/metabolomic analyses. RPS significantly increased MG-specific antibody levels and enhanced expression of the immunomodulatory cytokines, while suppressing that of pro-inflammatory factors. It also promoted tracheal mucosal integrity by elevating goblet cell numbers and mucosal epithelial height. Through metagenomic and metabolomic analysis, RPS was found to enrich the respiratory bacterium <i>Lactobacillus</i> sp. UMNPBX13, which was positively correlated with the metabolite phosphatidylcholine (PC). Intranasal administration of <i>Lactobacillus</i> increased mucin 2 (<i>MUC2</i>) and PC levels in tracheal mucosa. Similarly, PC combined with MGAV enhanced mucosal immunity by modulating cytokines and increasing MG-specific antibodies. These findings demonstrate that RPS enhances MGAV-induced respiratory mucosal immunity and provides a novel adjuvant strategy for improving poultry respiratory disease vaccines by modulating the respiratory microbiota, specifically through enrichment of <i>Lactobacillus</i> sp. UMNPBX13, which promotes PC production.IMPORTANCE<i>Mycoplasma gallisepticum</i> (MG) constitutes a notable challenge to poultry health. Although the MG-attenuated vaccine (MGAV) is widely used for disease control, it often fails to induce robust mucosal immunity. Here, we demonstrate that intranasal co-administration of <i>Radix Pseudostellariae</i> saponins (RPS) with MGAV augments mucosal immunoprotection. Integrated metagenomic and metabolomic analyses revealed that RPS enriches respiratory <i>Lactobacillus</i>, which in turn promotes the production of its key metabolite phosphatidylcholine (PC), thereby supporting mucosal immune enhancement. These findings offer a promising strategy for improving poultry vaccine efficacy and may provide a basis for future exploration of mucosal vaccination approaches in other animal species.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0078126"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The FERM guild: a differentially correlated microbial module drives hypertension via metabolic flux perturbations.","authors":"Wenkai Lai, Yuchen Zhang, Shaoping Huang, Shirong Lai, Fuxin Lin, Ziwei Wang, Shanwen Sun, Fenglong Yang","doi":"10.1128/msystems.00358-26","DOIUrl":"10.1128/msystems.00358-26","url":null,"abstract":"<p><p>Hypertension is a major risk factor for cardiovascular diseases, with changes in gut microbiota composition and function being closely associated with its onset and progression. However, the high inter-individual variability in gut microbiota complicates the identification of pathogenic mechanisms using traditional methods. In contrast, the smaller variability in gut microbial metabolites offers a more reliable and consistent basis for cross-individual comparisons. Parsimonious flux balance analysis (pFBA), integrated with double machine learning (DoubleML), identified 17 metabolites significantly associated with hypertension (<i>P</i> < 0.05, robustness value [RV] >0.1). These included meso-2,6-diaminoheptanedioate, p-hydroxyphenylacetic acid, cellobiose, dextran 40 (1,6-α-D-glucan), L-glutamic acid, and kestopentaose, among others. Differential microbial correlation network analysis identified a key microbial subnetwork, termed the FERM guild, consisting of 19 species, with prominent genera including <i>Faecalibacterium, Enterobacter, Roseburia</i>, and <i>Methanobrevibacter</i>. Using Gene Set Enrichment Analysis (GSEA), the dysregulation of this guild was found to be strongly associated with a set of 17 hypertension-related metabolites (<i>P</i> = 0.017). Further analysis revealed that the contribution of FERM genera to key metabolites is significantly associated with blood pressure (<i>P</i> < 0.05), even without significant differences in their abundance; additionally, an imbalance exists between FERM genera and other species. Our findings reveal that hypertension is associated with a disruption of gut microbial diversity, structure, and metabolic function. Seventeen key metabolites related to blood pressure regulation were identified, exhibiting pro- or anti-hypertensive potential and linked to functional microbial modules. These results highlight the gut microbiota and its metabolites as promising targets for therapeutic intervention in hypertension.</p><p><strong>Importance: </strong>Hypertension remains a major global public health burden; however, most studies on its relationship with the gut microbiota rely on traditional species-abundance analyses, which are limited by substantial inter-individual variability. In contrast, microbial metabolites show greater stability across individuals and thus offer a more reliable entry point for mechanistic research. By integrating metabolic modeling, causal inference, and network analysis, this study identified 17 key metabolites significantly associated with blood pressure and uncovered a functionally coordinated microbial community (FERM) whose contribution to critical metabolic fluxes (rather than its taxonomic abundance) was closely linked to hypertension. These findings reveal a metabolite-centered mechanism connecting microbial functions to host blood pressure regulation and provide new potential targets for microbiome-based interventions.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0035826"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}