mSystems最新文献

{"title":"Gut microbiome mediates the associations between lifestyle factors and risk of colorectal high-risk adenoma: results from a population-based cohort study.","authors":"Kai Song, Jiahui Luo, Yuhan Zhang, Dong Wu, Hongda Chen, Min Dai","doi":"10.1128/msystems.00933-25","DOIUrl":"https://doi.org/10.1128/msystems.00933-25","url":null,"abstract":"<p><p>Lifestyle factors exert influence on the risk of colorectal cancer (CRC) and its precursors. However, the interaction between gut microbiota and lifestyle factors concerning colorectal high-risk adenomas (HRAs), as well as the specific microbial taxa implicated, remains underexplored. Here, we aimed to investigate the impact of common lifestyle factors on HRAs and to explore the potential mediating roles of gut microbiota in these effects. A total of 3,827 participants were enrolled from our multicenter CRC screening cohort. Lifestyle factors over the 12 months preceding enrollment were assessed via questionnaires. Fecal samples were collected upon enrollment and analyzed using 16S rRNA sequencing. Multivariate analyses were used to identify lifestyle-related risk factors for HRA, followed by the application of the multivariate association with linear models (MaAsLin2) to explore associations between microbiota and lifestyle risk factors, with causal mediation analysis employed to evaluate the gut microbiota's mediating effect between lifestyle factors and HRA risk. A total of 272 patients with HRA and 1,253 controls were included. Independent risk factors for HRA were identified as high body mass index, number of pack-years smoked >30, alcohol consumption >4 units/week. These lifestyle factors were significantly associated with the relative abundance of various microbial genera. Notably, genus <i>Fusobacterium</i> and <i>Tyzzerella 4</i> were found to partially mediate the increased risk of HRA due to alcohol and cigarette consumption, respectively. These findings provide new insights for microbiota-targeted interventions or lifestyle-based prevention strategies to reduce the risk of CRC, offering a novel and actionable approach to early prevention.IMPORTANCELifestyle choices, such as diet, smoking, and alcohol consumption, are known to influence colorectal cancer risk, but the role of gut bacteria in mediating this process remains underestimated. To address this gap, our study aimed to explore the connections between lifestyle factors, gut microbes, and colorectal precancerous growths, referred to as high-risk adenomas (HRAs). We observed a dual association whereby obesity, heavy smoking, and excessive alcohol consumption were linked to both an increased risk of HRAs and distinct changes in gut bacteria. Importantly, smoking and alcohol consumption are associated with increased cancer risk, in part, through certain bacteria such as genus <i>Fusobacterium</i> and <i>Tyzzerella 4</i>. These findings reveal how gut microbes may act as a hidden bridge between lifestyle and disease development. Our discovery of these microbial mediators reveals novel opportunities for HRA prevention through lifestyle modifications or probiotic interventions targeting this carcinogenic pathway prior to malignant transformation.CLINICAL TRIALSThis study is registered with the Chinese Clinical Trial Registry as ChiCTR1800015506.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0093325"},"PeriodicalIF":4.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113828","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":"Global wastewater microbiome reveals core bacterial community and viral diversity with regional antibiotic resistance patterns.","authors":"Yueyang Yan, Xiaoyan Zhao, Xingxing Liang, Ying Xue, Qichen Niu, Dong Li, Xianqi Zhou, Yaoming Li, Shikui Dong, Yunpeng Gai","doi":"10.1128/msystems.01428-24","DOIUrl":"https://doi.org/10.1128/msystems.01428-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Municipal wastewater treatment plants (WWTPs) serve as global repositories for diverse and dynamic microbial communities, reflecting the complex interplay of human activities, environmental conditions, and public health challenges. Despite their importance, a comprehensive understanding of the global distribution, composition, and functional roles of these microbial ecosystems has remained elusive. Here, we present a comprehensive analysis of bacterial and viral diversities in global wastewater systems by examining 575 sampling sites across 74 cities in 60 countries. Through metagenomic analysis, we reconstructed 12,758 non-redundant bacterial metagenome-assembled genomes (MAGs) spanning 70 phyla, with 4,499 MAGs representing novel species. Despite considerable regional variation, we identified a consistent core microbiome present across 70% of global samples predominantly comprising Proteobacteria. We further assembled 1.7 million viral genomes, revealing unprecedented viral diversity with over 1.5 million species-level viral operational taxonomic units (vOTUs). Network analysis demonstrated that transport proteins play crucial roles in maintaining WWTP functional resilience against disturbances. Machine learning approaches effectively predicted continental origins of wastewater samples based on microbial signatures, confirming that microbial communities reflect local environmental and socioeconomic conditions while maintaining functional conservation. We observed significant variation in the antibiotic resistance gene (ARG) distribution, with elevated prevalence in certain African and Asian regions compared to Europe and North America. Our results establish wastewater microbiomes as important indicators of human activity and provide critical insights for advancing environmental monitoring, antimicrobial resistance surveillance, and wastewater-based epidemiology.IMPORTANCEIntensifying urbanization and human activities have dramatically increased global wastewater generation, creating complex microbial ecosystems that significantly impact environmental and public health. This study presents the first large-scale, comprehensive characterization of bacterial and viral communities in wastewater treatment systems worldwide. By analyzing samples from diverse geographical, climatic, and socioeconomic contexts, we reveal how wastewater microbiomes serve as microbial fingerprints of human society, reflecting regional characteristics while maintaining functional conservation. Our findings demonstrate that these communities function as ecological extensions of human gut microbiota in the external environment, with important implications for the spread of antibiotic resistance and pathogens. The identification of viruses as key metabolic regulators in these systems provides new perspectives on microbial community dynamics. This global-scale analysis advances our understanding of wastewater microbiology and offers valuable insights for improving wastew","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0142824"},"PeriodicalIF":4.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075692","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-cohort analysis unveils novel microbial targets for the treatment of hyperuricemia and gout.","authors":"Jinlong Qie, Man Cao, Min Xu, Yingjie Zhang, Liangen Luo, Chuqing Sun, Dongxian Ke, Songjian Yuan, Wenting Jia, Tianhua Qiu, Tianhua Li, Xiaoman Du, Chuanxing Xiao, Zhenqiang Hong, Bangzhou Zhang","doi":"10.1128/msystems.01091-25","DOIUrl":"https://doi.org/10.1128/msystems.01091-25","url":null,"abstract":"<p><p>The gut microbiota plays a crucial role in the development of hyperuricemia (HUA) and gout. However, the variability in study designs and analytical methods has led to inconsistent conclusions across different studies. Here, we conducted a comprehensive analysis of the gut microbiota associated with HUA and gout by examining 368 16S rRNA sequencing data from four Chinese cohorts, including 159 healthy controls (HC), 136 HUA patients, and 73 gout patients. Our findings indicate that there were significant differences in the gut microbiota composition between the three groups. Specifically, the HUA and gout groups demonstrated an increased abundance of pro-inflammatory bacteria, such as <i>Fusobacterium</i> and <i>Bilophila</i>, while beneficial bacteria known for their anti-inflammatory properties and metabolic benefits, including <i>Christensenellaceae</i> R-7 group, <i>Anaerostipes,</i> and <i>Collinsella</i>, are relatively reduced. Additionally, we developed a predictive model using microbial markers that achieved a high accuracy (area under the curve [AUC] > 0.8) in distinguishing between the HC, HUA, and gout groups. Notably, further metagenomic analysis identified a species-level genome bin (SGB), designated as <i>Phil1 sp00194085</i>, belonging to the order <i>Christensenellales</i>. For the first time, we discovered that this SGB carries a uric acid metabolic gene cluster and possesses enzymes associated with purine metabolism, suggesting its potential role in uric acid metabolism. Overall, our study deepens the understanding of the gut microbiota's role in HUA and gout and lays a foundation for developing innovative therapeutic strategies to effectively control uric acid levels through gut microbiota modulation.In this study, we conducted a comprehensive analysis of gut microbiota across multiple cohorts, identifying distinct microbial signatures in healthy controls, hyperuricemia (HUA), and gout patients. We observed an increase in pro-inflammatory bacteria and a decrease in beneficial bacteria for host metabolism in both the HUA and gout groups. Additionally, we developed a predictive model with high accuracy (area under the curve [AUC] > 0.8) based on microbial markers and discovered a novel species with potential for uric acid metabolism, providing new therapeutic targets for HUA and gout.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0109125"},"PeriodicalIF":4.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075783","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":"Exploring cervicovaginal microbiome differences between single and multiple endometrial polyps: implications for non-invasive classification.","authors":"Tianshu Sun, Qingyue Zheng, Roujie Huang, Leyan Yang, Zimo Liu, Zhibo Zhang, Xudong Liu, Hua Yang, Xiaochuan Li, Jiali Tong, Lan Zhu","doi":"10.1128/msystems.00023-25","DOIUrl":"https://doi.org/10.1128/msystems.00023-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Single and multiple endometrial polyps (EP) are common gynecological conditions with differing recurrence rates, influencing clinical treatment decisions. This study aimed to characterize the reproductive tract microbiome in both subtypes to support the development of methods for the non-invasive categorization of EPs. Using metagenomic sequencing, we analyzed vaginal and cervical samples from 27 reproductive-aged patients with single EP and 22 with multiple EP. Compared with controls and multiple EP cases, single EP vaginal and cervical samples exhibited a lower percentage of community state types (CST) I and II. &lt;i&gt;Sneathia amnii&lt;/i&gt; was identified as a characteristic species in both the vagina (&lt;i&gt;P&lt;/i&gt; = 0.0051) and cervix (&lt;i&gt;P&lt;/i&gt; = 0.0398) of single EP patients compared with controls. &lt;i&gt;Mesorhizobium&lt;/i&gt; sp. (vaginal &lt;i&gt;P&lt;/i&gt; = 0.0110, cervical &lt;i&gt;P&lt;/i&gt; = 0.0210), &lt;i&gt;Acinetobacter baumannii&lt;/i&gt; (vaginal &lt;i&gt;P&lt;/i&gt; = 8.0 × 10&lt;sup&gt;-5&lt;/sup&gt;, cervical &lt;i&gt;P&lt;/i&gt; = 0.0314), and &lt;i&gt;Pasteurella multocida&lt;/i&gt; (vaginal &lt;i&gt;P&lt;/i&gt; = 0.0173, cervical &lt;i&gt;P&lt;/i&gt; = 0.0210) were enriched in single EP compared with multiple EP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of vaginal microbiome revealed unique pathways in single EP, including aminoacyl-tRNA biosynthesis, pantothenate and coenzyme A (CoA) synthesis, pyrimidine metabolism, glycolysis/gluconeogenesis, and biosynthesis of phenylalanine, tyrosine, and tryptophan. Using a random forest model, we further selected microbiota and clinical parameters to differentiate single and multiple EPs, thus achieving an area under curve (AUC) of 0.861. Our findings characterized the composition of the cervicovaginal microbiota of single and multiple EPs and proposed biomarkers for their non-invasive classification based on a random forest model.IMPORTANCEThe prevalence rate of endometrial polyps (EPs), a common gynecological condition, varies between 7.8% and 34.9%. Multiple EPs are associated with higher recurrence rates and chronic endometritis than single EPs and thus require more aggressive clinical interventions. However, only laparoscopic surgery can accurately identify single and multiple polyps. Non-invasive adjunctive diagnostic methods can aid in altering surgical indications preoperatively. Using metagenomic sequencing, we thoroughly analyzed the vaginal and cervical samples of 27 single EP and 22 multiple EP patients of reproductive age. We then identified distinct microbial patterns in the single and multiple samples, which were crucial for understanding EP pathogenesis and its association with gynecological health. Using a random forest model, key bacterial taxa that differentiate single and multiple EPs were identified with high accuracy. These could potentially serve as non-invasive diagnostic biomarkers. This research delineates the cervicovaginal microbiome of the reproductive tract in EP patients, offering a basis for developing non-invasive diagnostic tools and persona","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0002325"},"PeriodicalIF":4.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065191","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 diversity and network analyses reveal drivers of microbiome dynamics.","authors":"Rui Guan, Ruben Garrido-Oter","doi":"10.1128/msystems.00564-25","DOIUrl":"https://doi.org/10.1128/msystems.00564-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Microbial communities are key components of ecosystems, where interactions among microbes drive biodiversity and productivity. An increased number of microbiome data sets are available, owing to advances in sequencing; however, standard analyses often focus on community composition, neglecting the complex interactions between co-occurring microbes. To address this, we developed a computational framework integrating compositional and co-occurrence network analyses. We applied this approach to extensive microbial amplicon data sets, focusing on plant microbiota, which typically exhibits high diversity and remains challenging to characterize due to the large number of low-abundance taxa. We show that identifying a subset of representative microbial taxa captures the overall community structure and increases the statistical power. From these taxa, we inferred a large-scale co-occurrence network and clustered microbes with co-varying abundances into units for diversity measurement. This approach not only reduces unexplained variance in diversity assessments but also captures the key microbe-microbe relationships that govern assembly patterns. Furthermore, we introduced a bootstrap- and permutation-based statistical approach to compare microbial networks from diverse conditions. Our method robustly distinguishes meaningful differences and pinpoints specific microbes and features driving those differences. These results highlight the importance of incorporating microbe-microbe interactions in microbiota studies, leading to more accurate and ecologically meaningful insights. Our framework, available as an R package (\"mina\"), enables researchers to identify condition-specific interactions &lt;i&gt;via&lt;/i&gt; network comparison and gain a deeper understanding of community ecology. With broad applicability beyond plant systems, this package provides a valuable tool for leveraging microbiome data across disciplines, from agriculture to ecosystem resilience and human health.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Understanding microbiome dynamics requires capturing not only changes in microbial composition but also interactions between community members. Traditional approaches frequently overlook microbe-microbe interactions, limiting their ecological interpretation. Here, we introduce a novel computational framework that integrates compositional data with network-based analyses, significantly improving the detection of biologically meaningful patterns in community variation. By applying this framework to a large data set from the plant microbiota, we identify representative groups of interacting microbes driving differences across microhabitats and environmental conditions. Our analysis framework, implemented in an R package \"mina,\" provides robust tools allowing researchers to assess statistical differences between microbial networks and detect condition-specific interactions. Broadly applicable to microbiome data sets, our framework is aimed at enabling advances ","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0056425"},"PeriodicalIF":4.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065208","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":"Discovery of novel hammerhead, twister, and DVRz-associated circular RNAs in <i>Vitaceae</i>, <i>Solanaceae,</i> and <i>Rosaceae</i>.","authors":"Ali Raza, Yu Zhu, Ming'an Deng, Qingfa Wu","doi":"10.1128/msystems.01168-25","DOIUrl":"https://doi.org/10.1128/msystems.01168-25","url":null,"abstract":"<p><p>Viroids and viroid-like exogenous circular RNAs (ex-circRNAs) are small infectious RNA agents capable of autonomous replication within host cells, independent of any helper virus. In this study, we analyzed rRNA-depleted transcriptomic data sets from members of the <i>Vitaceae</i>, <i>Solanaceae</i>, and <i>Rosaceae</i> families to explore the diversity of these subviral elements. Using both homology-based and alignment-free ribozyme detection methods, we recovered 16 known viroids and identified 13 novel viroid-like RNAs from plant metatranscriptomic data sets. Among these, we report two new hammerhead ribozyme-containing viroid-like RNAs-CGHVd-RNA in <i>Physalis peruviana</i> and GPLMVd-RNA in <i>Vitis vinifera</i>-that display distinct secondary structures and limited sequence similarity to known viroids, supporting their classification as new species within the <i>Avsunviroidae</i> family. We also identified a symmetric twister ribozyme-containing ex-circRNA in peach, with validated <i>in vitro</i> self-cleavage activity. Additionally, three ambi-like circular RNAs were detected in grapevine and peach, encoding divergent RNA-dependent RNA polymerases, hairpin (HP), and delta virus ribozymes (DVRz). Finally, a novel Obelisk-like RNA with unique structural features was discovered in the Cape gooseberry. These results reveal the hidden complexity and broad host range of plant-associated viroid-like RNAs and suggest the existence of previously unrecognized subviral lineages with distinct evolutionary origins.IMPORTANCEThis study reveals remarkable diversity in plant-associated subviral RNA populations, identifying 13 novel viroid-like RNAs alongside 16 known viroids. Notable discoveries include new hammerhead ribozyme-containing species-level ex-circRNAs from Cape gooseberry and grapevine, a symmetric twister ribozyme ex-circRNA in peach, and, surprisingly, ambi-like circular RNAs with RNA-dependent RNA polymerases. These findings significantly expand our understanding of the complexity and evolutionary diversity of plant-associated subviral RNAs.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0116825"},"PeriodicalIF":4.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065180","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":"Machine learning-based evaluation of risk factors for carbapenem-resistant <i>Klebsiella pneumoniae</i> dissemination in neonatal units.","authors":"Xiao Liu, Muxiu Jiang, Jinzhi Zhang, Heng Li, Yina Liu, Jiaqi Zhang, Xia Chen, Jun Bu, Shichang Xie, Menghan Zhang, Ning Dong, Qing Cao, Zhemin Zhou","doi":"10.1128/msystems.00909-25","DOIUrl":"https://doi.org/10.1128/msystems.00909-25","url":null,"abstract":"<p><p>Healthcare-associated infections (HAIs), particularly in neonatal intensive care units (NICUs), pose significant challenges due to neonates' vulnerability and the rapid infection spread. However, risk factors facilitating pathogen persistence and dissemination have not been comprehensively investigated. This study aims to track HAI transmission pathways in NICUs and identify key risk factors contributing to the persistence and spread of carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP). We analyzed CRKP epidemiology and population dynamics in neonatal patients at a pediatric hospital in China over 8 years. Random forest models identified primary risk factors for CRKP persistence and outbreaks, focusing on clonal spread, healthcare groups (HGs), and plasmid dynamics. Three major clonal outbreaks involving ST14 and ST433 strains were identified, highlighting the critical role of clonal dissemination in NICUs. Complex transmission patterns, characterized by periods of dormancy and resurgence, suggest the existence of underlying reservoirs. HGs were implicated in the short-term transmission of CRKP, with >80% of infection clusters involving patients from the same HG. Plasmids emerged as critical factors in the long-term persistence of CRKP, with shifts in plasmid prevalence corresponding to outbreak periods. This study advances our understanding of CRKP transmission dynamics in NICUs, highlighting the multifaceted roles of clonal dissemination, HGs, and plasmid-mediated persistence. Our findings emphasize the need for enhanced infection control measures targeting both intra- and inter-group transmissions and plasmid surveillance.IMPORTANCEThis study provides a detailed analysis of carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) transmission dynamics in neonatal intensive care units (NICUs) over eight years, utilizing 64 isolates and applying machine learning to identify risk factors associated with persistence and spread. Through phylogenetic analyses, we uncovered three clonal outbreaks and linked healthcare group (HG) interactions, bacterial genotypes, and plasmid prevalence to short- and long-term CRKP transmission. We identified that HGs are primary mediators of rapid, short-term transmission, while specific plasmids play an extended role in maintaining CRKP presence across multiple patient cohorts and bacterial strains. This finding suggests the existence of latent reservoirs or periodic reintroductions from external sources, thus reshaping the understanding of NICU-associated pathogen transmission and persistence.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0090925"},"PeriodicalIF":4.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065204","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 analysis reveals important role for microbial-derived metabolites from <i>Botryllus schlosseri</i> in metal interactions.","authors":"Dulce G Guillén Matus, Caroline M Donaghy, Nidhi Vijayan, Zachary T Lane, Matthew Howell, George G Glavin, Alfredo M Angeles-Boza, Spencer V Nyholm, Marcy J Balunas","doi":"10.1128/msystems.00793-25","DOIUrl":"https://doi.org/10.1128/msystems.00793-25","url":null,"abstract":"<p><p>Marine microbial communities govern many of the biological and chemical processes in the ocean, including element cycles, ecosystem health, and disease. Marine organisms are surrounded by microbes, with complex molecular interactions occurring between bacterial symbionts, eukaryotic hosts, and their pathogens or prey. Trace metals in the ocean can be either beneficial or detrimental to marine life depending on their concentrations and bioavailability. Multiple marine tunicate species are known to bioaccumulate trace metals in their mantel, and research suggests that tunicate microbiota plays an important role in this process. <i>Botryllus schlosseri</i>, a marine colonial tunicate, has become a model organism for cellular and developmental studies, yet its ecological interactions are still not well understood. Using an integrated multidisciplinary approach, we established a comprehensive baseline and explored correlations between members of the <i>B. schlosseri</i> microbiome, metabolome, and metallome to elucidate the ecological effects of trace metals in host-microbe-pathogen interactions. We identified significant correlations between metals, including manganese, nickel, cerium, zinc, and cobalt, with various metabolites and bacterial taxa. These findings offer insights into <i>B. schlosseri</i>'s biological and chemical interactions with microorganisms and their environment, contributing to bridging the knowledge gap of host-microbiome-environment interactions and establishing a foundation for continuing research on the ecological effects of trace metals in these biological systems.IMPORTANCEGiven the importance of marine invertebrates and their microbial communities in marine ecosystems, we sought to characterize the largely unknown microbial associates, metal sequestration, and metabolite production of the marine colonial tunicate, <i>Botryllus schlosseri</i>, a model organism for cellular and developmental studies. Using an integrated multidisciplinary approach, we identified significant correlations between metals, metabolites, and bacterial taxa. <i>B. schlosseri</i> tissue was highly enriched in metals compared to seawater, and <i>B. schlosseri</i> microbiome beta-diversity was significantly different from seawater. We also introduced the concept of the pan-metabolome to classify metabolites based on their presence or absence across complex samples and found microbial metabolites in both the core and flexible metabolome. These findings offer insights into <i>B. schlosseri</i>'s biological and chemical interactions with microorganisms and their environment, bridging the knowledge gap of host-microbiome-environment interactions and establishing a foundation for continuing research on the ecological effects of trace metals in these biological systems.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0079325"},"PeriodicalIF":4.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065176","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":"Effect of immune-related intratumoral microbiota and host gene expression on cancer prognosis.","authors":"Qingzhen Fu, Ning Zhao, Xia Li, Yanbing Li, Tian Tian, Lijing Gao, Yukun Cao, Liwan Wang, Jinyin Liu, Fan Wang, Yanlong Liu, Binbin Cui, Yashuang Zhao","doi":"10.1128/msystems.01146-25","DOIUrl":"https://doi.org/10.1128/msystems.01146-25","url":null,"abstract":"<p><p>The intratumoral microbiota has been identified as an indispensable part of the tumor microenvironment (TME). However, the relationship between the intratumoral microbiota and host gene expression, as well as its impact on prognosis and TME immunity, remains unclear. We utilized a machine learning-based framework to identify microbiota-host gene associations across 14 tumors from The Cancer Genome Atlas (TCGA) and validated them in 11 tumors from the Gene Expression Omnibus. By calculating immune scores and identifying immune-related microbiota, we developed both a pan-cancer Immune and Prognosis-Related Microbial Score (IPRMS) and cancer-specific IPRMSs and analyzed the relationship between the cancer-specific IPRMSs and immune infiltration at bulk level and single-cell level. Furthermore, we systematically analyzed the potential mechanisms in which the intratumoral microbiota might affect prognosis using survival mediation analyses (SMAs). We identified gene subsets associated with microbiota, which were predominantly enriched in immune-related and cell signaling regulation pathways. Subsequently, we constructed the overall survival-related IPRMS and found that high-IPRMS patients had poorer prognosis in pan-cancer and increased presence of macrophage and cancer-associated fibroblasts. In contrast, low-IPRMS patients showed enrichment in tumor-infiltrating lymphocytes. SMAs suggest that intratumoral microbiota may influence prognosis by affecting immune cells, pathways, and host genes. High-IPRMSs were consistently associated with poorer prognosis and lower abundance of tumor-infiltrating lymphocytes. At the single-cell level, cancer-associated fibroblasts were predominantly enriched in the high-IPRMS group, while tumor-infiltrating lymphocytes were also mainly enriched in the low-IPRMS group. Our research indicates that the intratumoral microbiota was associated with immune and prognosis, which may impact the cancer prognosis by modifying immune cells, pathways, and host gene expression.</p><p><strong>Importance: </strong>The intratumoral microbiota is a vital part of the tumor microenvironment, yet its interplay with host gene expression and immune regulation remains unclear. Based on a machine learning framework for the interaction analysis of intratumoral microbiota and host genes, as well as the construction of the Immune and Prognosis-Related Microbial Score, our findings suggest that intratumoral microbiota may influence gene expression by affecting host pathways, especially immune-related pathways. Moreover, immune-related intratumoral microbiota are significantly associated with patient survival and TME immunity and may influence prognosis by affecting immune cells, pathways, or gene expression, offering new perspectives and potential biomarkers for predicting personalized patient prognosis in the future.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0114625"},"PeriodicalIF":4.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065206","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":"Bacterial taxonomic and functional changes following oral lyophilized donor fecal microbiota transplantation in patients with ulcerative colitis.","authors":"Shreeya S Raich, Marwan E Majzoub, Craig Haifer, Sudarshan Paramsothy, Md Mushahidul Islam Shamim, Thomas J Borody, Rupert W Leong, Nadeem O Kaakoush","doi":"10.1128/msystems.00991-25","DOIUrl":"https://doi.org/10.1128/msystems.00991-25","url":null,"abstract":"<p><p>Oral lyophilized fecal microbiota transplantation (FMT) can induce remission in patients with active ulcerative colitis (UC); however, our understanding of how this form of FMT alters the patient microbiome remains limited. Here, we analyzed data from a recent randomized, double-blind, placebo-controlled clinical trial of FMT in UC to assess donor species colonization and factors responsible for efficacy using this form of therapy. The gut microbiome of donors and patients was profiled longitudinally using deep shotgun metagenomic sequencing, and microbiome diversity, species-genome bin presence, functional profiles, and the resistome were studied. The gut microbiome of patients treated with oral lyophilized FMT significantly increased in species-genome bin richness and shifted in composition toward the donor profiles; this was not observed in patients receiving placebo. While species-genome bin richness was not associated with clinical response in this trial, we identified donor- and patient-specific features associated with the induction of remission and maintenance of response. However, the presence of a <i>Clostridium</i> species-genome bin, as well as L-citrulline biosynthesis contributed by <i>Alistipes</i> spp., was seen in responders treated by either donor. Several of the above outcomes were found to be consistent when data were analyzed at the level of metagenome-assembled genomes. FMT was also found to deplete the resistome within patients treated with antibiotics to levels lower than the UC baseline. Single donor oral lyophilized FMT substantially modifies taxonomic diversity and composition as well as microbiome function and the resistome in patients with UC, with several features identified as strongly linked to response regardless of the donor used.</p><p><strong>Importance: </strong>There is a limited amount of work examining the effects of oral lyophilized fecal microbiota transplantation (FMT) on the microbiome of patients with ulcerative colitis (UC), and less so studies examining species-level dynamics and functional changes using this form of FMT. We performed deep shotgun metagenomic sequencing to provide an in-depth species-genome bin-level analysis of the microbiome of patients with UC receiving oral lyophilized FMT from a single donor. We identified key taxonomic and functional features that transferred into patients and were associated with clinical response. We also determined how FMT impacts the resistome of patients with UC. We believe these findings will be important in ongoing efforts to not only improve the efficacy of FMT in UC but also allow for the transition to defined microbial therapeutics, foregoing the need for FMT donors.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0099125"},"PeriodicalIF":4.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065220","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}