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Population diversity and accelerated mutation drive anaerobic bacterial adaptation during long-term solvent stress. 种群多样性和加速突变驱动厌氧菌适应长期溶剂胁迫。
IF 5.2 2区 生物学
mSystems Pub Date : 2026-10-05 DOI: 10.1128/msystems.00454-26
Tom Zaplana, Magali Boutard, Ivan Dubois, William Rostain, Veronique de Berardinis, Volker Doring, Henri-Pierre Fierobe, Andrew C Tolonen
{"title":"Population diversity and accelerated mutation drive anaerobic bacterial adaptation during long-term solvent stress.","authors":"Tom Zaplana, Magali Boutard, Ivan Dubois, William Rostain, Veronique de Berardinis, Volker Doring, Henri-Pierre Fierobe, Andrew C Tolonen","doi":"10.1128/msystems.00454-26","DOIUrl":"https://doi.org/10.1128/msystems.00454-26","url":null,"abstract":"<p><p>Experimental evolution can uncover general mechanisms by which microorganisms adapt to environmental stress. Here, we investigate evolutionary trajectories of the anaerobic, lignocellulose-fermenting bacterium <i>Lachnoclostridium phytofermentans</i> ISDg (family <i>Lachnospiraceae</i>) during >2,000 generations of automated, log-phase selection at progressively increasing butanol concentrations. Evolved clones showed large gains in fitness, reaching threefold-faster growth rates in standard medium, and robust growth at concentrations of butanol and other alcohols inhibitory to the parental strain. Longitudinal genome sequencing revealed the succession of genetic changes, including expansion of ISL3 insertion sequences, activation of a cryptic phosphotransferase system, and mutations leading to increased cell size and remodeling of membrane fatty acids. The fixation of a hypermutator genotype by generation 940 preceded a burst of genetic diversity and accelerated adaptation, followed by population destabilization as the mutational load accumulated. These findings provide insights into the mechanisms by which anaerobes acquire tolerance to industrially relevant stresses during adaptive laboratory evolution.IMPORTANCELong-term growth selection under controlled conditions can be applied to dissect complex, multigenic traits such as solvent tolerance. Butanol is an industrial solvent whose toxicity remains a major barrier to its efficient microbial production. We adapted <i>Lachnoclostridium phytofermentans</i> ISDg, a lignocellulose-fermenting, strictly anaerobic bacterium, to increasing butanol concentrations by automated cultivation with alternating periods of constant or variable butanol selection pressure. Evolved strains grew faster and tolerated solvent concentrations that completely inhibited the parental strain, attaining tolerance levels similar to those of native butanol producers. Genome analysis identified both previously recognized and novel adaptive changes, revealing how prolonged solvent tolerance arises through the interplay of mobile genetic elements, cellular restructuring, and altered mutation rates.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0045426"},"PeriodicalIF":5.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112297","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}
引用次数: 0
Leviathan: fast, memory-efficient, and scalable taxonomic and pathway profiling for (pan)genome-resolved metagenomics and metatranscriptomics. 利维坦:快速,内存效率高,可扩展的(泛)基因组解析元基因组学和元转录组学的分类和途径分析。
IF 5.2 2区 生物学
mSystems Pub Date : 2026-10-05 DOI: 10.1128/msystems.00970-26
Josh L Espinoza, Allan J Phillips, Chris L Dupont
{"title":"Leviathan: fast, memory-efficient, and scalable taxonomic and pathway profiling for (pan)genome-resolved metagenomics and metatranscriptomics.","authors":"Josh L Espinoza, Allan J Phillips, Chris L Dupont","doi":"10.1128/msystems.00970-26","DOIUrl":"https://doi.org/10.1128/msystems.00970-26","url":null,"abstract":"<p><p>Functional profiling of meta-omics is essential for understanding microbial communities, yet support for custom genome-resolved reference databases is limited. We introduce Leviathan for integrated taxonomic and functional profiling at both genome and pangenome resolution. Leviathan combines Sylph for ultrafast alignment-free taxonomic profiling with Salmon for pseudo-alignment-based read quantification in DNA space against (pan)genome-resolved gene catalogs, producing dual metrics per (pan)genome: pathway abundance and graph-based pathway coverage. Benchmarking alignment backends on synthetic metagenomes, we show that DNA-space pseudo-alignments retain competitive (pan)genome-level classification performance compared to traditional alignment, reducing resource requirements, while translated searches in protein space lose classification resolution from ambiguous mapping events. Leviathan's utility is demonstrated through two case studies: a marine plastisphere metagenomics data set analyzing metabolic shifts between early and mature biofilm communities, and a dental caries metatranscriptomics data set where co-expression network analysis identified organism-specific transcriptional patterns diagnostic of health and disease states. Leviathan is available at https://github.com/jolespin/leviathan.IMPORTANCEUnderstanding what microbes can do, not just which ones are present, is central to translating microbiome research into actionable insight. Existing functional profiling tools either rely on fixed reference databases or require complex multi-step pipelines when applied to custom genome collections, and none natively compute per-(pan)genome pathway abundance and graph-based pathway completeness in a single workflow. This limits the ability for researchers to directly compare functional profiles to tangential analyses on their specific genome catalogs. Leviathan addresses this gap with integrated taxonomic and functional profiling against user-defined (pan)genome-resolved references using pseudo-alignment, achieving competitive classification accuracy, with lower resource requirements compared to current methods. Native pangenome support enables routine quantification of metabolic potential and transcriptional activity at both genome and pangenome resolution, revealing functional variation across related strains that single-genome or community-level analyses obscure.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0097026"},"PeriodicalIF":5.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112278","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}
引用次数: 0
Iron-dependent metabolic rewiring drives tryptophan-associated melanin production in a clinical Pseudomonas aeruginosa strain. 铁依赖的代谢重新布线驱动色氨酸相关的黑色素生产在临床铜绿假单胞菌菌株。
IF 5.2 2区 生物学
mSystems Pub Date : 2026-10-05 DOI: 10.1128/msystems.01035-26
Mateo N Diaz Appella, Adriana A Kolender, Mulugeta Nega, Stefania A Robaldi, Pablo M Cassanelli, Ningna Li, Elisa Liberini, Pablo Hoijemberg, Darío A Fernández Do Porto, Leonardo Pelliza, Martin Aran, Friedrich Götz, Nancy I López, Paula M Tribelli
{"title":"Iron-dependent metabolic rewiring drives tryptophan-associated melanin production in a clinical <i>Pseudomonas aeruginosa</i> strain.","authors":"Mateo N Diaz Appella, Adriana A Kolender, Mulugeta Nega, Stefania A Robaldi, Pablo M Cassanelli, Ningna Li, Elisa Liberini, Pablo Hoijemberg, Darío A Fernández Do Porto, Leonardo Pelliza, Martin Aran, Friedrich Götz, Nancy I López, Paula M Tribelli","doi":"10.1128/msystems.01035-26","DOIUrl":"https://doi.org/10.1128/msystems.01035-26","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> is a human opportunistic pathogen, capable of producing a wide range of metabolites, including pyomelanin, which results from alterations in tyrosine catabolism. In contrast, melanin synthesis from tryptophan has never been reported in <i>Pseudomonas</i>. In this study, we applied an integrated multi-omics approach to characterize physiological adaptations associated with the emergence of a tryptophan-associated melanin-like pigment in <i>P. aeruginosa</i> PAH, a persistently re-isolated strain from a cystic fibrosis patient. Structural analysis revealed the production of a previously unreported melanin-like polymer produced under tryptophan supplementation, coexisting with a pyomelanin-like soluble fraction. This melanin exhibited iron-reduction capacity, supporting a potential physiological role in iron acquisition within the infective niche. Genome analysis identified mutations affecting iron acquisition, including genes involved in pyoverdine biosynthesis. Transcriptomic profiling revealed a coordinated reprogramming of iron homeostasis, characterized not only by the downregulation of pyoverdine-associated genes but also by altered expression of alternative siderophore systems and a broader set of genes, such as redox response pathways. Non-targeting metabolomic analyses uncovered the accumulation of indole-derived compounds. Inhibitors of tyrosine and tryptophan catabolism demonstrated a metabolic shift between these pathways. Notably, iron availability emerged as a key regulator of this system, with iron limitation promoting pigment production and associated metabolic states. Integrating these data sets, we developed an integrative model linking iron homeostasis, genomic variation, transcriptional and metabolic reprogramming, and melanin production in <i>P. aeruginosa</i> PAH. Overall, tryptophan arises as a key compound for melanin production in a <i>Pseudomonas</i> strain, expanding the diversity of melanins synthesized by this genus.IMPORTANCEThis study reveals a previously unrecognized way by which <i>Pseudomonas aeruginosa</i> can produce melanin, a protective pigment linked to survival and persistence in hostile environments. Here, we report how a novel melanin pigment, produced in tryptophan-supplemented media, can reduce iron and is linked to iron homeostasis in a clinical <i>P. aeruginosa</i> strain. Employing a multi-omics approach, we show that this pathway operates primarily through anthranilate and indolic intermediates and is favored under iron-limited conditions. This finding deepens current understanding about pigment diversity in bacteria and highlights the remarkable metabolic flexibility of <i>P. aeruginosa</i> during infection. Since the same phenotype was observed again in year-later isolates from the same patient, our results suggest a potential role of this trait in long-term infection and adaptation.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0103526"},"PeriodicalIF":5.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112225","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}
引用次数: 0
A hyphal release-capture soil microcosm for recovering hyphosphere bacterial communities. 菌丝释放捕获土壤微观环境用于恢复土壤细菌群落。
IF 5.2 2区 生物学
mSystems Pub Date : 2026-10-02 DOI: 10.1128/msystems.01096-26
Gayan Abeysinghe, Elek Nagy, Tanya Wagner, Shravan Parunandi, Joshua Santos, Muthukumar Bagavathiannan, Sanjay Antony-Babu
{"title":"A hyphal release-capture soil microcosm for recovering hyphosphere bacterial communities.","authors":"Gayan Abeysinghe, Elek Nagy, Tanya Wagner, Shravan Parunandi, Joshua Santos, Muthukumar Bagavathiannan, Sanjay Antony-Babu","doi":"10.1128/msystems.01096-26","DOIUrl":"https://doi.org/10.1128/msystems.01096-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Fungal hyphae form spatially confined interfaces in soil that mediate close associations with bacteria, collectively referred to as the hyphosphere. Despite its recognized ecological importance, experimental access to hyphosphere-associated microbial communities under realistic soil and plant-associated conditions has remained limited. Here, we present a soil-mimetic microcosm that enables controlled recovery of hyphosphere bacterial communities embedded within plant-associated soil. The system integrates field-derived soil, a native soil microbial inoculum, living cotton seedlings, and a spatially constrained fungal inoculum housed within sterile cell-strainer assemblies, permitting hyphal extension into soil while preserving a recoverable fungal-soil boundary. Using the soil-borne plant pathogen &lt;i&gt;Fusarium oxysporum&lt;/i&gt; f. sp. &lt;i&gt;vasinfectum&lt;/i&gt; as a model filamentous fungus, we show that the microcosm enables reproducible recovery of hypha-associated soil microaggregates containing physically attached bacterial cells. Full-length 16S rRNA profiling revealed pronounced reductions in bacterial richness and evenness in hyphosphere samples relative to bulk and rhizosphere soils (Shannon diversity, Kruskal-Wallis &lt;i&gt;H&lt;/i&gt; = 15.25, &lt;i&gt;P&lt;/i&gt; = 0.0016, with genus richness declining by 87% in bulk soil and 24% in rhizosphere soil contexts), consistent with recruitment of a restricted subset of the surrounding microbiota. Ordination analyses demonstrated clear compositional separation between soil and hyphosphere compartments (PERMANOVA &lt;i&gt;F&lt;/i&gt; = 7.14, &lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.572, &lt;i&gt;P&lt;/i&gt; = 0.001), with hyphosphere communities of bulk and rhizosphere origin converging to similar composition despite differing starting soils (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.128, &lt;i&gt;P&lt;/i&gt; = 0.307). Phylogenetic turnover analyses (βNTI) indicated phylogenetic structuring (exceeding the +2 threshold), whereas taxonomic analyses identified a conserved set of bacterial genera consistently associated with hyphae, alongside compartment-specific taxa influenced by soil and plant context. Together, these findings establish the novel hyphal release-and-capture microcosm as a reproducible, ecologically grounded platform for studying hyphosphere-associated bacterial communities in plant-associated soils.IMPORTANCESoil fungi recruit distinct bacterial communities along their hyphae, forming a specialized microhabitat known as the hyphosphere. Despite its ecological importance, studying hyphosphere-associated bacteria under realistic plant-soil conditions has remained experimentally difficult. Here, we present a soil-mimetic hyphal release-capture microcosm that enables controlled reconstruction and recovery of bacterial communities assembled along fungal hyphae in intact plant-associated soils. Using the cotton wilt pathogen &lt;i&gt;Fusarium oxysporum&lt;/i&gt; f. sp. &lt;i&gt;vasinfectum&lt;/i&gt;, we show that fungal hyphae reproducibly recruit reduced and compositionally distinct bacterial assemblages","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0109626"},"PeriodicalIF":5.2,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112306","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}
引用次数: 0
The quantitative amino acid economy of yeast reveals public versus private goods and guides syntrophic community design. 酵母的定量氨基酸经济揭示了公共产品与私人产品的对比,并指导了共生群落的设计。
IF 5.2 2区 生物学
mSystems Pub Date : 2026-09-22 Epub Date: 2026-08-07 DOI: 10.1128/msystems.00333-26
Shabbir Ahmad, Ganesh Muthu, Sunil Laxman
{"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}
引用次数: 0
The iModulon framework: how x-AI reveals microbial regulatory logic. iModulon框架:x-AI如何揭示微生物调控逻辑。
IF 5.2 2区 生物学
mSystems Pub Date : 2026-09-22 Epub Date: 2026-08-12 DOI: 10.1128/msystems.00228-26
Kangsan Kim, Edward Alexander Catoiu, Yongjae Lee, Dukwon Lee, Chaewon Lee, Jiwon Lee, Jongoh Shin, Bernhard Palsson, Byung-Kwan Cho
{"title":"The iModulon framework: how x-AI reveals microbial regulatory logic.","authors":"Kangsan Kim, Edward Alexander Catoiu, Yongjae Lee, Dukwon Lee, Chaewon Lee, Jiwon Lee, Jongoh Shin, Bernhard Palsson, Byung-Kwan Cho","doi":"10.1128/msystems.00228-26","DOIUrl":"10.1128/msystems.00228-26","url":null,"abstract":"<p><p>The accelerating deposition of RNAseq data over the past decade has motivated the development of advanced transcriptomic data analytics that can operate on a large number of samples. One successful approach is to apply independent component analysis (ICA) to large prokaryotic transcriptomic compendia to decompose them into independently modulated gene sets, called iModulons. Here, we review the data science principles underlying ICA-based transcriptome decomposition, computational workflows that support its routine application, and iModulonDB infrastructure that hosts and disseminates the resulting decompositions. We present iModulonDB 3.0 that contains 53 species and 71 ICA decompositions across 33,062 RNA-seq samples, with several well-sampled species (e.g., <i>Escherichia coli</i>, <i>Bacillus subtilis</i>, <i>Staphylococcus aureus, Pseudomonas aeruginosa</i>) represented by more than one compendium. With 71 standardized decompositions, we demonstrate systematic cross-species comparison of species-specific iModulon structures. This comparison identifies a shared \"regulatory toolkit\" of 13 modules conserved across distantly related bacteria, alongside a long tail of lineage-specific programs. We assess the design principles and limitations governing iModulon reconstruction and computation. Together, these advances position the iModulon framework as an accessible, community-driven approach for reading accumulating public transcriptomes as reusable regulatory programs, enabling biological discovery and module-level design in synthetic biology.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0022826"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713100","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}
引用次数: 0
Integrated multi-omics analysis identifies microbial and metabolic signatures and drivers of CNS autoimmunity. 综合多组学分析确定了微生物和代谢特征以及中枢神经系统自身免疫的驱动因素。
IF 5.2 2区 生物学
mSystems Pub Date : 2026-09-22 Epub Date: 2026-08-11 DOI: 10.1128/msystems.00002-26
Theresa L Montgomery, Emily A Nelson, Lauren A Downs, Eamonn R Heney, Margaret Frances J Lee, Cameron Martino, Daniel McDonald, Gibraan Rahman, Rob Knight, Dimitry N Krementsov
{"title":"Integrated multi-omics analysis identifies microbial and metabolic signatures and drivers of CNS autoimmunity.","authors":"Theresa L Montgomery, Emily A Nelson, Lauren A Downs, Eamonn R Heney, Margaret Frances J Lee, Cameron Martino, Daniel McDonald, Gibraan Rahman, Rob Knight, Dimitry N Krementsov","doi":"10.1128/msystems.00002-26","DOIUrl":"10.1128/msystems.00002-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), driven by genetic and environmental determinants. The gut microbiome of people with MS (pwMS) is distinct and influences disease through immunomodulatory metabolite production. Circulating metabolites are altered in pwMS, but identifying microbial-metabolic drivers remains challenging. We previously showed that colonization by the gut commensal &lt;i&gt;Limosilactobacillus reuteri&lt;/i&gt; exacerbates disease in the experimental autoimmune encephalomyelitis (EAE) model of MS in a tryptophan-dependent manner. Here, we integrated microbiomic and metabolomic data sets from a longitudinal EAE study utilizing high- and low-tryptophan diets in mice colonized with or without &lt;i&gt;L. reuteri&lt;/i&gt;. Gut microbiome dynamics, under short- and long-term alterations in tryptophan bioavailability, were affected by diet, microbiome context, or disease. During short-term dietary intervention, &lt;i&gt;L. reuteri&lt;/i&gt; colonization exerted a greater impact on microbiome composition than tryptophan bioavailability. With longer dietary exposure and EAE progression, high dietary tryptophan and &lt;i&gt;L. reuteri&lt;/i&gt; colonization synergized to elicit profound microbiota changes, including alterations in Lachnospiraceae, &lt;i&gt;Blautia,&lt;/i&gt; and &lt;i&gt;Akkermansia&lt;/i&gt;. Integration of metabolomic and microbiomic data sets using joint Robust Aitchison PCA revealed clusters of associated metabolites and microbiota enriched for functional pathways, including bile acid and tryptophan metabolism. Metabolites outperformed microbiota in predicting EAE severity, identifying p-cresols and indoles as top disease-associated metabolites. Treatment with p-cresol or 3-indoleglyoxylic acid exacerbated EAE, enhanced proinflammatory T-cell responses, and increased cerebellar pathology. These data demonstrate that dietary responses are shaped by gut microbiome composition and that integrated microbiomic-metabolomic analyses can identify the drivers of disease worsening in MS.IMPORTANCEMultiple sclerosis (MS) is a multifactorial disease influenced not only by genetics but also by environmental factors, potentially including diet and the composition of the gut microbiome. We show that interactions between diet and commensal gut microbiota profoundly impact the levels of immunomodulatory systemic metabolites, including several that are associated with disease in people with MS (pwMS). Importantly, we demonstrate that individual gut microbiota-produced metabolites are sufficient to worsen disease in a mouse model of MS. Integration of gut microbiome and blood metabolite data sets, combined with subsequent predictive modeling, may bolster biomarker identification and the capacity to predict disease severity in pwMS, as compared to the performance of individual data sets alone. These findings highlight metabolites as key mediators linking diet and the gut microbiota to neuroinflammation. Importantly, this work suggests that targeting micr","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0000226"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707116","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}
引用次数: 0
Erratum for Firrman et al., "An in vitro model of the small intestinal microbiota provides key insights into interindividual variability in structure and function". Firrman等人的勘误,“小肠微生物群的体外模型提供了对结构和功能的个体间差异的关键见解”。
IF 5.2 2区 生物学
mSystems Pub Date : 2026-09-22 Epub Date: 2026-08-05 DOI: 10.1128/msystems.00999-26
Jenni Firrman, LinShu Liu, Karley Mahalak, Johanna M S Lemons, Adrienne Narrowe, Elliot S Friedman, Gary D Wu, Tom Van de Wiele
{"title":"Erratum for Firrman et al., \"An <i>in vitro</i> model of the small intestinal microbiota provides key insights into interindividual variability in structure and function\".","authors":"Jenni Firrman, LinShu Liu, Karley Mahalak, Johanna M S Lemons, Adrienne Narrowe, Elliot S Friedman, Gary D Wu, Tom Van de Wiele","doi":"10.1128/msystems.00999-26","DOIUrl":"10.1128/msystems.00999-26","url":null,"abstract":"","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0099926"},"PeriodicalIF":5.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674050","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}
引用次数: 0
Multi-kingdom gut microbiota analyses identify biomarkers of different types of pediatric short bowel syndrome. 多领域肠道微生物群分析确定不同类型儿科短肠综合征的生物标志物。
IF 5.2 2区 生物学
mSystems Pub Date : 2026-09-22 Epub Date: 2026-09-01 DOI: 10.1128/msystems.00316-26
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
{"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}
引用次数: 0
Ancestral hydrocarbon metabolism enables PET degradation by a natural bacterial consortium. 祖先的碳氢化合物代谢使PET降解的自然细菌财团。
IF 5.2 2区 生物学
mSystems Pub Date : 2026-09-22 Epub Date: 2026-08-21 DOI: 10.1128/msystems.00829-26
Sabrina Edwards, Danny Rice, Patricio Palomino, Irene Newton, Jay L Mellies
{"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}
引用次数: 0
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