Pub Date : 2024-10-22Epub Date: 2024-09-30DOI: 10.1128/msystems.00615-24
Iida Loivamaa, Annika Sillanpää, Paulina Deptula, Bhawani Chamlagain, Minnamari Edelmann, Petri Auvinen, Tuula A Nyman, Kirsi Savijoki, Vieno Piironen, Pekka Varmanen
Propionibacterium freudenreichii (PFR) DSM 20271T is a bacterium known for its ability to thrive in diverse environments and to produce vitamin B12. Despite its anaerobic preference, recent studies have elucidated its ability to prosper in the presence of oxygen, prompting a deeper exploration of its physiology under aerobic conditions. Here, we investigated the response of DSM 20271T to aerobic growth by employing comparative transcriptomic and surfaceome analyses alongside metabolite profiling. Cultivation under controlled partial pressure of oxygen (pO2) conditions revealed significant increases in biomass formation and altered metabolite production, notably of vitamin B12, pseudovitamin-B12, propionate, and acetate, under aerobic conditions. Transcriptomic analysis identified differential expression of genes involved in lactate metabolism, tricarboxylic acid cycle, and electron transport chain, suggesting metabolic adjustments to aerobic environments. Moreover, surfaceome analysis unveiled growth environment-dependent changes in surface protein abundance, with implications for adaptation to atmospheric conditions. Supplementation experiments with key compounds highlighted the potential for enhancing aerobic growth, emphasizing the importance of iron and α-ketoglutarate availability. Furthermore, in liquid culture, FeSO4 supplementation led to increased heme production and reduced vitamin B12 production, highlighting the impact of oxygen and iron availability on the metabolic pathways. These findings deepen our understanding of PFR's physiological responses to oxygen availability and offer insights for optimizing its growth in industrial applications.
Importance: The study of the response of Propionibacterium freudenreichii to aerobic growth is crucial for understanding how this bacterium adapts to different environments and produces essential compounds like vitamin B12. By investigating its physiological changes under aerobic conditions, we can gain insights into its metabolic adjustments and potential for enhanced growth. These findings not only deepen our understanding of P. freudenreichii's responses to oxygen availability but also offer valuable information for optimizing its growth in industrial applications. This research sheds light on the adaptive mechanisms of this bacterium, providing a foundation for further exploration and potential applications in various fields.
{"title":"Aerobic adaptation and metabolic dynamics of <i>Propionibacterium freudenreichii</i> DSM 20271: insights from comparative transcriptomics and surfaceome analysis.","authors":"Iida Loivamaa, Annika Sillanpää, Paulina Deptula, Bhawani Chamlagain, Minnamari Edelmann, Petri Auvinen, Tuula A Nyman, Kirsi Savijoki, Vieno Piironen, Pekka Varmanen","doi":"10.1128/msystems.00615-24","DOIUrl":"10.1128/msystems.00615-24","url":null,"abstract":"<p><p><i>Propionibacterium freudenreichii</i> (<i>PFR</i>) DSM 20271<sup>T</sup> is a bacterium known for its ability to thrive in diverse environments and to produce vitamin B12. Despite its anaerobic preference, recent studies have elucidated its ability to prosper in the presence of oxygen, prompting a deeper exploration of its physiology under aerobic conditions. Here, we investigated the response of DSM 20271<sup>T</sup> to aerobic growth by employing comparative transcriptomic and surfaceome analyses alongside metabolite profiling. Cultivation under controlled partial pressure of oxygen (pO<sub>2</sub>) conditions revealed significant increases in biomass formation and altered metabolite production, notably of vitamin B12, pseudovitamin-B12, propionate, and acetate, under aerobic conditions. Transcriptomic analysis identified differential expression of genes involved in lactate metabolism, tricarboxylic acid cycle, and electron transport chain, suggesting metabolic adjustments to aerobic environments. Moreover, surfaceome analysis unveiled growth environment-dependent changes in surface protein abundance, with implications for adaptation to atmospheric conditions. Supplementation experiments with key compounds highlighted the potential for enhancing aerobic growth, emphasizing the importance of iron and α-ketoglutarate availability. Furthermore, in liquid culture, FeSO<sub>4</sub> supplementation led to increased heme production and reduced vitamin B12 production, highlighting the impact of oxygen and iron availability on the metabolic pathways. These findings deepen our understanding of <i>PFR</i>'s physiological responses to oxygen availability and offer insights for optimizing its growth in industrial applications.</p><p><strong>Importance: </strong>The study of the response of <i>Propionibacterium freudenreichii</i> to aerobic growth is crucial for understanding how this bacterium adapts to different environments and produces essential compounds like vitamin B12. By investigating its physiological changes under aerobic conditions, we can gain insights into its metabolic adjustments and potential for enhanced growth. These findings not only deepen our understanding of <i>P. freudenreichii'</i>s responses to oxygen availability but also offer valuable information for optimizing its growth in industrial applications. This research sheds light on the adaptive mechanisms of this bacterium, providing a foundation for further exploration and potential applications in various fields.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350371","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}
Pub Date : 2024-10-22Epub Date: 2024-09-24DOI: 10.1128/msystems.00782-24
Meora Rajeev, Ilsuk Jung, Ilnam Kang, Jang-Cheon Cho
<p><p>Bioflocs are microbial aggregates that play a pivotal role in shaping animal health, gut microbiota, and water quality in biofloc technology (BFT)-based aquaculture systems. Despite the worldwide application of BFT in aquaculture industries, our comprehension of the community composition and functional potential of the floc-associated microbiota (FAB community; ≥3 µm size fractions) remains rudimentary. Here, we utilized genome-centric metagenomic approach to investigate the FAB community in shrimp aquaculture systems, resulting in the reconstruction of 520 metagenome-assembled genomes (MAGs) spanning both bacterial and archaeal domains. Taxonomic analysis identified <i>Pseudomonadota</i> and <i>Bacteroidota</i> as core community members, with approximately 93% of recovered MAGs unclassified at the species level, indicating a large uncharacterized phylogenetic diversity hidden in the FAB community. Functional annotation of these MAGs unveiled their complex carbohydrate-degrading potential and involvement in carbon, nitrogen, and sulfur metabolisms. Specifically, genomic evidence supported ammonium assimilation, autotrophic nitrification, denitrification, dissimilatory nitrate reduction to ammonia, thiosulfate oxidation, and sulfide oxidation pathways, suggesting the FAB community's versatility for both aerobic and anaerobic metabolisms. Conversely, genes associated with heterotrophic nitrification, anaerobic ammonium oxidation, assimilatory nitrate reduction, and sulfate reduction were undetected. Members of <i>Rhodobacteraceae</i> emerged as the most abundant and metabolically versatile taxa in this intriguing community. Our MAGs compendium is expected to expand the available genome collection from such underexplored aquaculture environments. By elucidating the microbial community structure and metabolic capabilities, this study provides valuable insights into the key biogeochemical processes occurring in biofloc aquacultures and the major microbial contributors driving these processes.</p><p><strong>Importance: </strong>Biofloc technology has emerged as a sustainable aquaculture approach, utilizing microbial aggregates (bioflocs) to improve water quality and animal health. However, the specific microbial taxa within this intriguing community responsible for these benefits are largely unknown. Compounding this challenge, many bacterial taxa resist laboratory cultivation, hindering taxonomic and genomic analyses. To address these gaps, we employed metagenomic binning approach to recover over 500 microbial genomes from floc-associated microbiota of biofloc aquaculture systems operating in South Korea and China. Through taxonomic and genomic analyses, we deciphered the functional gene content of diverse microbial taxa, shedding light on their potential roles in key biogeochemical processes like nitrogen and sulfur metabolisms. Notably, our findings underscore the taxa-specific contributions of microbes in aquaculture environments, particularl
生物絮团是一种微生物聚集体,在基于生物絮团技术(BFT)的水产养殖系统中对动物健康、肠道微生物群和水质的形成起着关键作用。尽管生物絮团技术在水产养殖业中的应用遍及全球,但我们对絮团相关微生物群(FAB 群,≥3 µm 大小的部分)的群落组成和功能潜力的了解仍然很有限。在这里,我们利用以基因组为中心的元基因组学方法研究了对虾养殖系统中的絮凝物群落,重建了 520 个元基因组组装基因组(MAGs),涵盖了细菌和古细菌两个领域。分类学分析确定假单胞菌和类杆菌为群落的核心成员,约 93% 的已恢复 MAGs 在物种水平上未分类,这表明在 FAB 群落中隐藏着大量未定性的系统发育多样性。对这些 MAGs 的功能注释揭示了它们复杂的碳水化合物降解潜力,以及参与碳、氮和硫代谢的情况。具体来说,基因组证据支持氨同化、自养硝化、反硝化、硝酸盐异纤还原成氨、硫代硫酸盐氧化和硫化物氧化途径,这表明 FAB 群落在好氧和厌氧代谢方面具有多功能性。相反,与异养硝化、厌氧铵氧化、同化作用硝酸盐还原和硫酸盐还原相关的基因却未被检测到。在这一引人入胜的群落中,罗杆菌科成员是数量最多、代谢能力最强的类群。我们的 MAGs 汇编有望扩大此类未充分开发的水产养殖环境中的可用基因组收集。通过阐明微生物群落结构和代谢能力,本研究为了解生物絮团水产养殖中发生的关键生物地球化学过程以及驱动这些过程的主要微生物贡献者提供了宝贵的见解:生物絮团技术已成为一种可持续的水产养殖方法,它利用微生物聚集体(生物絮团)来改善水质和动物健康。然而,在这一引人入胜的群落中,产生这些益处的具体微生物类群却大多不为人知。此外,许多细菌类群对实验室培养有抵触情绪,阻碍了分类学和基因组学分析。为了填补这些空白,我们采用了元基因组分选方法,从韩国和中国生物絮团水产养殖系统的絮团相关微生物群中恢复了 500 多个微生物基因组。通过分类和基因组分析,我们破译了不同微生物类群的功能基因含量,揭示了它们在氮和硫代谢等关键生物地球化学过程中的潜在作用。值得注意的是,我们的研究结果强调了水产养殖环境中微生物类群的特定贡献,尤其是在复杂的碳降解和去除氨、硝酸盐和硫化物等有毒物质方面。
{"title":"Genome-centric metagenomics provides insights into the core microbial community and functional profiles of biofloc aquaculture.","authors":"Meora Rajeev, Ilsuk Jung, Ilnam Kang, Jang-Cheon Cho","doi":"10.1128/msystems.00782-24","DOIUrl":"10.1128/msystems.00782-24","url":null,"abstract":"<p><p>Bioflocs are microbial aggregates that play a pivotal role in shaping animal health, gut microbiota, and water quality in biofloc technology (BFT)-based aquaculture systems. Despite the worldwide application of BFT in aquaculture industries, our comprehension of the community composition and functional potential of the floc-associated microbiota (FAB community; ≥3 µm size fractions) remains rudimentary. Here, we utilized genome-centric metagenomic approach to investigate the FAB community in shrimp aquaculture systems, resulting in the reconstruction of 520 metagenome-assembled genomes (MAGs) spanning both bacterial and archaeal domains. Taxonomic analysis identified <i>Pseudomonadota</i> and <i>Bacteroidota</i> as core community members, with approximately 93% of recovered MAGs unclassified at the species level, indicating a large uncharacterized phylogenetic diversity hidden in the FAB community. Functional annotation of these MAGs unveiled their complex carbohydrate-degrading potential and involvement in carbon, nitrogen, and sulfur metabolisms. Specifically, genomic evidence supported ammonium assimilation, autotrophic nitrification, denitrification, dissimilatory nitrate reduction to ammonia, thiosulfate oxidation, and sulfide oxidation pathways, suggesting the FAB community's versatility for both aerobic and anaerobic metabolisms. Conversely, genes associated with heterotrophic nitrification, anaerobic ammonium oxidation, assimilatory nitrate reduction, and sulfate reduction were undetected. Members of <i>Rhodobacteraceae</i> emerged as the most abundant and metabolically versatile taxa in this intriguing community. Our MAGs compendium is expected to expand the available genome collection from such underexplored aquaculture environments. By elucidating the microbial community structure and metabolic capabilities, this study provides valuable insights into the key biogeochemical processes occurring in biofloc aquacultures and the major microbial contributors driving these processes.</p><p><strong>Importance: </strong>Biofloc technology has emerged as a sustainable aquaculture approach, utilizing microbial aggregates (bioflocs) to improve water quality and animal health. However, the specific microbial taxa within this intriguing community responsible for these benefits are largely unknown. Compounding this challenge, many bacterial taxa resist laboratory cultivation, hindering taxonomic and genomic analyses. To address these gaps, we employed metagenomic binning approach to recover over 500 microbial genomes from floc-associated microbiota of biofloc aquaculture systems operating in South Korea and China. Through taxonomic and genomic analyses, we deciphered the functional gene content of diverse microbial taxa, shedding light on their potential roles in key biogeochemical processes like nitrogen and sulfur metabolisms. Notably, our findings underscore the taxa-specific contributions of microbes in aquaculture environments, particularl","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308106","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}
Pub Date : 2024-10-22Epub Date: 2024-09-04DOI: 10.1128/msystems.00171-24
Rogelio A Rodriguez-Gonzalez, Quentin Balacheff, Laurent Debarbieux, Jacopo Marchi, Joshua S Weitz
<p><p>Infections caused by multidrug resistant (MDR) pathogenic bacteria are a global health threat. Bacteriophages ("phage") are increasingly used as alternative or last-resort therapeutics to treat patients infected by MDR bacteria. However, the therapeutic outcomes of phage therapy may be limited by the emergence of phage resistance during treatment and/or by physical constraints that impede phage-bacteria interactions <i>in vivo</i>. In this work, we evaluate the role of lung spatial structure on the efficacy of phage therapy for <i>Pseudomonas aeruginosa</i> infections. To do so, we developed a spatially structured metapopulation network model based on the geometry of the bronchial tree, including host innate immune responses and the emergence of phage-resistant bacterial mutants. We model the ecological interactions between bacteria, phage, and the host innate immune system at the airway (node) level. The model predicts the synergistic elimination of a <i>P. aeruginosa</i> infection due to the combined effects of phage and neutrophils, given the sufficient innate immune activity and efficient phage-induced lysis. The metapopulation model simulations also predict that MDR bacteria are cleared faster at distal nodes of the bronchial tree. Notably, image analysis of lung tissue time series from wild-type and lymphocyte-depleted mice revealed a concordant, statistically significant pattern: infection intensity cleared in the bottom before the top of the lungs. Overall, the combined use of simulations and image analysis of <i>in vivo</i> experiments further supports the use of phage therapy for treating acute lung infections caused by <i>P. aeruginosa,</i> while highlighting potential limits to therapy in a spatially structured environment given impaired innate immune responses and/or inefficient phage-induced lysis.</p><p><strong>Importance: </strong>Phage therapy is increasingly employed as a compassionate treatment for severe infections caused by multidrug-resistant (MDR) bacteria. However, the mixed outcomes observed in larger clinical studies highlight a gap in understanding when phage therapy succeeds or fails. Previous research from our team, using <i>in vivo</i> experiments and single-compartment mathematical models, demonstrated the synergistic clearance of acute <i>P. aeruginosa</i> pneumonia by phage and neutrophils despite the emergence of phage-resistant bacteria. In fact, the lung environment is highly structured, prompting the question of whether immunophage synergy explains the curative treatment of <i>P. aeruginosa</i> when incorporating realistic physical connectivity. To address this, we developed a metapopulation network model mimicking the lung branching structure to assess phage therapy efficacy for MDR <i>P. aeruginosa</i> pneumonia. The model predicts the synergistic elimination of <i>P. aeruginosa</i> by phage and neutrophils but emphasizes potential challenges in spatially structured environments, suggesting that higher
{"title":"Metapopulation model of phage therapy of an acute <i>Pseudomonas aeruginosa</i> lung infection.","authors":"Rogelio A Rodriguez-Gonzalez, Quentin Balacheff, Laurent Debarbieux, Jacopo Marchi, Joshua S Weitz","doi":"10.1128/msystems.00171-24","DOIUrl":"10.1128/msystems.00171-24","url":null,"abstract":"<p><p>Infections caused by multidrug resistant (MDR) pathogenic bacteria are a global health threat. Bacteriophages (\"phage\") are increasingly used as alternative or last-resort therapeutics to treat patients infected by MDR bacteria. However, the therapeutic outcomes of phage therapy may be limited by the emergence of phage resistance during treatment and/or by physical constraints that impede phage-bacteria interactions <i>in vivo</i>. In this work, we evaluate the role of lung spatial structure on the efficacy of phage therapy for <i>Pseudomonas aeruginosa</i> infections. To do so, we developed a spatially structured metapopulation network model based on the geometry of the bronchial tree, including host innate immune responses and the emergence of phage-resistant bacterial mutants. We model the ecological interactions between bacteria, phage, and the host innate immune system at the airway (node) level. The model predicts the synergistic elimination of a <i>P. aeruginosa</i> infection due to the combined effects of phage and neutrophils, given the sufficient innate immune activity and efficient phage-induced lysis. The metapopulation model simulations also predict that MDR bacteria are cleared faster at distal nodes of the bronchial tree. Notably, image analysis of lung tissue time series from wild-type and lymphocyte-depleted mice revealed a concordant, statistically significant pattern: infection intensity cleared in the bottom before the top of the lungs. Overall, the combined use of simulations and image analysis of <i>in vivo</i> experiments further supports the use of phage therapy for treating acute lung infections caused by <i>P. aeruginosa,</i> while highlighting potential limits to therapy in a spatially structured environment given impaired innate immune responses and/or inefficient phage-induced lysis.</p><p><strong>Importance: </strong>Phage therapy is increasingly employed as a compassionate treatment for severe infections caused by multidrug-resistant (MDR) bacteria. However, the mixed outcomes observed in larger clinical studies highlight a gap in understanding when phage therapy succeeds or fails. Previous research from our team, using <i>in vivo</i> experiments and single-compartment mathematical models, demonstrated the synergistic clearance of acute <i>P. aeruginosa</i> pneumonia by phage and neutrophils despite the emergence of phage-resistant bacteria. In fact, the lung environment is highly structured, prompting the question of whether immunophage synergy explains the curative treatment of <i>P. aeruginosa</i> when incorporating realistic physical connectivity. To address this, we developed a metapopulation network model mimicking the lung branching structure to assess phage therapy efficacy for MDR <i>P. aeruginosa</i> pneumonia. The model predicts the synergistic elimination of <i>P. aeruginosa</i> by phage and neutrophils but emphasizes potential challenges in spatially structured environments, suggesting that higher","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126171","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}
Pub Date : 2024-10-22Epub Date: 2024-09-05DOI: 10.1128/msystems.00788-24
Luyao Liu, Lin Ma, Huan Liu, Fan Zhao, Pu Li, Junhua Zhang, Xin Lü, Xin Zhao, Yanglei Yi
Systemic inflammatory response syndrome (SIRS) is a severe inflammatory response that can lead to organ dysfunction and death. Modulating the gut microbiome is a promising therapeutic approach for managing SIRS. This study assesses the therapeutic potential of the Xuanfei Baidu (XFBD) formula in treating SIRS. The results showed that XFBD administration effectively reduced mortality rates and inflammation in SIRS mice. Using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we substantiated that the therapeutic effects of XFBD are partly attributed to gut microbiota modulation. We conducted in vitro experiments to accurately assess the gut microbiome remodeling effects of 51 compounds isolated from XFBD. These compounds exhibited varying abilities to induce a microbial structure that closely resembles that of the healthy control group. By quantifying their impact on microbial structure and clustering their regulatory patterns, we devised multiple gut microbiome remodeling compound (GMRC) cocktails. GMRC cocktail C, comprising aucubin, gentiopicroside, syringic acid, gallic acid, p-hydroxybenzaldehyde, para-hydroxybenzoic acid, and isoimperatorin, demonstrated superior efficacy in treating SIRS compared to a single compound or to other cocktails. Finally, in vitro experiments showcased that GMRC cocktail C effectively rebalanced bacteria composition in SIRS patients. This study underscores XFBD's therapeutic potential in SIRS and highlights the importance of innovative treatment approaches for this disease by targeting the gut microbiota.IMPORTANCEDeveloping effective treatment strategies for systemic inflammatory response syndrome (SIRS) is crucial due to its severe and often life-threatening nature. While traditional treatments like dexamethasone have shown efficacy, they also come with significant side effects and limitations. This study makes significant strides by demonstrating that the Xuanfei Baidu (XFBD) formula can substantially reduce mortality rates and inflammation in SIRS mice through effective modulation of the gut microbiota. By quantitatively assessing the impact of 51 compounds derived from XFBD on the gut microbiome, we developed a potent gut microbiome remodeling compound cocktail. This cocktail outperformed individual compounds and other mixtures in efficacy against SIRS. These findings highlight the potential of XFBD as a therapeutic solution for SIRS and underscore the critical role of innovative strategies targeting the gut microbiota in addressing this severe inflammatory condition.
{"title":"Targeted discovery of gut microbiome-remodeling compounds for the treatment of systemic inflammatory response syndrome.","authors":"Luyao Liu, Lin Ma, Huan Liu, Fan Zhao, Pu Li, Junhua Zhang, Xin Lü, Xin Zhao, Yanglei Yi","doi":"10.1128/msystems.00788-24","DOIUrl":"10.1128/msystems.00788-24","url":null,"abstract":"<p><p>Systemic inflammatory response syndrome (SIRS) is a severe inflammatory response that can lead to organ dysfunction and death. Modulating the gut microbiome is a promising therapeutic approach for managing SIRS. This study assesses the therapeutic potential of the Xuanfei Baidu (XFBD) formula in treating SIRS. The results showed that XFBD administration effectively reduced mortality rates and inflammation in SIRS mice. Using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we substantiated that the therapeutic effects of XFBD are partly attributed to gut microbiota modulation. We conducted <i>in vitro</i> experiments to accurately assess the gut microbiome remodeling effects of 51 compounds isolated from XFBD. These compounds exhibited varying abilities to induce a microbial structure that closely resembles that of the healthy control group. By quantifying their impact on microbial structure and clustering their regulatory patterns, we devised multiple gut microbiome remodeling compound (GMRC) cocktails. GMRC cocktail C, comprising aucubin, gentiopicroside, syringic acid, gallic acid, p-hydroxybenzaldehyde, para-hydroxybenzoic acid, and isoimperatorin, demonstrated superior efficacy in treating SIRS compared to a single compound or to other cocktails. Finally, <i>in vitro</i> experiments showcased that GMRC cocktail C effectively rebalanced bacteria composition in SIRS patients. This study underscores XFBD's therapeutic potential in SIRS and highlights the importance of innovative treatment approaches for this disease by targeting the gut microbiota.IMPORTANCEDeveloping effective treatment strategies for systemic inflammatory response syndrome (SIRS) is crucial due to its severe and often life-threatening nature. While traditional treatments like dexamethasone have shown efficacy, they also come with significant side effects and limitations. This study makes significant strides by demonstrating that the Xuanfei Baidu (XFBD) formula can substantially reduce mortality rates and inflammation in SIRS mice through effective modulation of the gut microbiota. By quantitatively assessing the impact of 51 compounds derived from XFBD on the gut microbiome, we developed a potent gut microbiome remodeling compound cocktail. This cocktail outperformed individual compounds and other mixtures in efficacy against SIRS. These findings highlight the potential of XFBD as a therapeutic solution for SIRS and underscore the critical role of innovative strategies targeting the gut microbiota in addressing this severe inflammatory condition.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133249","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}
Pub Date : 2024-10-22Epub Date: 2024-10-01DOI: 10.1128/msystems.00888-24
Clément Coclet, Antonio Pedro Camargo, Simon Roux
While numerous computational frameworks and workflows are available for recovering prokaryote and eukaryote genomes from metagenome data, only a limited number of pipelines are designed specifically for viromics analysis. With many viromics tools developed in the last few years alone, it can be challenging for scientists with limited bioinformatics experience to easily recover, evaluate quality, annotate genes, dereplicate, assign taxonomy, and calculate relative abundance and coverage of viral genomes using state-of-the-art methods and standards. Here, we describe Modular Viromics Pipeline (MVP) v.1.0, a user-friendly pipeline written in Python and providing a simple framework to perform standard viromics analyses. MVP combines multiple tools to enable viral genome identification, characterization of genome quality, filtering, clustering, taxonomic and functional annotation, genome binning, and comprehensive summaries of results that can be used for downstream ecological analyses. Overall, MVP provides a standardized and reproducible pipeline for both extensive and robust characterization of viruses from large-scale sequencing data including metagenomes, metatranscriptomes, viromes, and isolate genomes. As a typical use case, we show how the entire MVP pipeline can be applied to a set of 20 metagenomes from wetland sediments using only 10 modules executed via command lines, leading to the identification of 11,656 viral contigs and 8,145 viral operational taxonomic units (vOTUs) displaying a clear beta-diversity pattern. Further, acting as a dynamic wrapper, MVP is designed to continuously incorporate updates and integrate new tools, ensuring its ongoing relevance in the rapidly evolving field of viromics. MVP is available at https://gitlab.com/ccoclet/mvp and as versioned packages in PyPi and Conda.IMPORTANCEThe significance of our work lies in the development of Modular Viromics Pipeline (MVP), an integrated and user-friendly pipeline tailored exclusively for viromics analyses. MVP stands out due to its modular design, which ensures easy installation, execution, and integration of new tools and databases. By combining state-of-the-art tools such as geNomad and CheckV, MVP provides high-quality viral genome recovery and taxonomy and host assignment, and functional annotation, addressing the limitations of existing pipelines. MVP's ability to handle diverse sample types, including environmental, human microbiome, and plant-associated samples, makes it a versatile tool for the broader microbiome research community. By standardizing the analysis process and providing easily interpretable results, MVP enables researchers to perform comprehensive studies of viral communities, significantly advancing our understanding of viral ecology and its impact on various ecosystems.
{"title":"MVP: a modular viromics pipeline to identify, filter, cluster, annotate, and bin viruses from metagenomes.","authors":"Clément Coclet, Antonio Pedro Camargo, Simon Roux","doi":"10.1128/msystems.00888-24","DOIUrl":"10.1128/msystems.00888-24","url":null,"abstract":"<p><p>While numerous computational frameworks and workflows are available for recovering prokaryote and eukaryote genomes from metagenome data, only a limited number of pipelines are designed specifically for viromics analysis. With many viromics tools developed in the last few years alone, it can be challenging for scientists with limited bioinformatics experience to easily recover, evaluate quality, annotate genes, dereplicate, assign taxonomy, and calculate relative abundance and coverage of viral genomes using state-of-the-art methods and standards. Here, we describe Modular Viromics Pipeline (MVP) v.1.0, a user-friendly pipeline written in Python and providing a simple framework to perform standard viromics analyses. MVP combines multiple tools to enable viral genome identification, characterization of genome quality, filtering, clustering, taxonomic and functional annotation, genome binning, and comprehensive summaries of results that can be used for downstream ecological analyses. Overall, MVP provides a standardized and reproducible pipeline for both extensive and robust characterization of viruses from large-scale sequencing data including metagenomes, metatranscriptomes, viromes, and isolate genomes. As a typical use case, we show how the entire MVP pipeline can be applied to a set of 20 metagenomes from wetland sediments using only 10 modules executed via command lines, leading to the identification of 11,656 viral contigs and 8,145 viral operational taxonomic units (vOTUs) displaying a clear beta-diversity pattern. Further, acting as a dynamic wrapper, MVP is designed to continuously incorporate updates and integrate new tools, ensuring its ongoing relevance in the rapidly evolving field of viromics. MVP is available at https://gitlab.com/ccoclet/mvp and as versioned packages in PyPi and Conda.IMPORTANCEThe significance of our work lies in the development of Modular Viromics Pipeline (MVP), an integrated and user-friendly pipeline tailored exclusively for viromics analyses. MVP stands out due to its modular design, which ensures easy installation, execution, and integration of new tools and databases. By combining state-of-the-art tools such as geNomad and CheckV, MVP provides high-quality viral genome recovery and taxonomy and host assignment, and functional annotation, addressing the limitations of existing pipelines. MVP's ability to handle diverse sample types, including environmental, human microbiome, and plant-associated samples, makes it a versatile tool for the broader microbiome research community. By standardizing the analysis process and providing easily interpretable results, MVP enables researchers to perform comprehensive studies of viral communities, significantly advancing our understanding of viral ecology and its impact on various ecosystems.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11498083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350275","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}
Pub Date : 2024-10-21DOI: 10.1128/msystems.00620-24
Sarah E Daly, Jingzhang Feng, Devin Daeschel, Jasna Kovac, Abigail B Snyder
Accurate knowledge of the microbiota collected from surfaces in food processing environments is important for food quality and safety. This study assessed discrepancies in taxonomic composition and alpha and beta diversity values generated from eight different bioinformatic workflows for the analysis of 16S rRNA gene sequences extracted from the microbiota collected from surfaces in dairy processing environments. We found that the microbiota collected from environmental surfaces varied widely in density (0-9.09 log10 CFU/cm2) and Shannon alpha diversity (0.01-3.40). Consequently, depending on the sequence analysis method used, characterization of low-abundance genera (i.e., below 1% relative abundance) and the number of genera identified (114-173 genera) varied considerably. Some low-abundance genera, including Listeria, varied between the amplicon sequence variant (ASV) and operational taxonomic unit (OTU) methods. Centered log-ratio transformation inflated alpha and beta diversity values compared to rarefaction. Furthermore, the ASV method also inflated alpha and beta diversity values compared to the OTU method (P < 0.05). Therefore, for sparse, uneven, low-density data sets, the OTU method and rarefaction are better for taxonomic and ecological characterization of surface microbiota.IMPORTANCECulture-dependent environmental monitoring programs are used by the food industry to identify foodborne pathogens and spoilage biota on surfaces in food processing environments. The use of culture-independent 16S rRNA amplicon sequencing to characterize this surface microbiota has been proposed as a tool to enhance environmental monitoring. However, there is no consensus on the most suitable bioinformatic analyses to accurately capture the diverse levels and types of bacteria on surfaces in food processing environments. Here, we quantify the impact of different bioinformatic analyses on the results and interpretation of 16S rRNA amplicon sequences collected from three cultured dairy facilities in New York State. This study provides guidance for the selection of appropriate 16S rRNA analysis procedures for studying environmental microbiota in dairy processing environments.
{"title":"The choice of 16S rRNA gene sequence analysis impacted characterization of highly variable surface microbiota in dairy processing environments.","authors":"Sarah E Daly, Jingzhang Feng, Devin Daeschel, Jasna Kovac, Abigail B Snyder","doi":"10.1128/msystems.00620-24","DOIUrl":"https://doi.org/10.1128/msystems.00620-24","url":null,"abstract":"<p><p>Accurate knowledge of the microbiota collected from surfaces in food processing environments is important for food quality and safety. This study assessed discrepancies in taxonomic composition and alpha and beta diversity values generated from eight different bioinformatic workflows for the analysis of 16S rRNA gene sequences extracted from the microbiota collected from surfaces in dairy processing environments. We found that the microbiota collected from environmental surfaces varied widely in density (0-9.09 log<sub>10</sub> CFU/cm<sup>2</sup>) and Shannon alpha diversity (0.01-3.40). Consequently, depending on the sequence analysis method used, characterization of low-abundance genera (i.e., below 1% relative abundance) and the number of genera identified (114-173 genera) varied considerably. Some low-abundance genera, including <i>Listeria</i>, varied between the amplicon sequence variant (ASV) and operational taxonomic unit (OTU) methods. Centered log-ratio transformation inflated alpha and beta diversity values compared to rarefaction. Furthermore, the ASV method also inflated alpha and beta diversity values compared to the OTU method (<i>P</i> < 0.05). Therefore, for sparse, uneven, low-density data sets, the OTU method and rarefaction are better for taxonomic and ecological characterization of surface microbiota.IMPORTANCECulture-dependent environmental monitoring programs are used by the food industry to identify foodborne pathogens and spoilage biota on surfaces in food processing environments. The use of culture-independent 16S rRNA amplicon sequencing to characterize this surface microbiota has been proposed as a tool to enhance environmental monitoring. However, there is no consensus on the most suitable bioinformatic analyses to accurately capture the diverse levels and types of bacteria on surfaces in food processing environments. Here, we quantify the impact of different bioinformatic analyses on the results and interpretation of 16S rRNA amplicon sequences collected from three cultured dairy facilities in New York State. This study provides guidance for the selection of appropriate 16S rRNA analysis procedures for studying environmental microbiota in dairy processing environments.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470285","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}
Pub Date : 2024-10-21DOI: 10.1128/msystems.00623-24
Yanqiu Wei, Juanjuan Shi, Jianhua Wang, Zongyan Hu, Min Wang, Wen Wang, Xiujuan Cui
The objectives of this study are to examine the disparities in serum and intestinal tissue metabolites between a perimenopausal rat model and control rats and to analyze the diversity and functionality of intestinal microorganisms to determine the potential correlation between intestinal flora and metabolites. We established a rat model of perimenopausal syndrome (PMS) and performed an integrated analysis of metabolome and microbiome. Orthogonal partial least-squares discriminant analysis scores and replacement tests indicated distinct separations of anion and cation levels between serum and intestinal samples of the model and control groups. Furthermore, lipids and lipid-like molecules constituted the largest percentage of HMDB compounds in both serum and intestinal tissues, followed by organic acids and derivatives, and organoheterocyclic compounds, with other compounds showing significant variability. Moreover, analysis of diversity and functional enrichment of the intestinal microflora and correlation analysis with metabolites revealed significant variability in the composition of the intestinal flora between the normal control and perimenopausal groups, with these differentially expressed intestinal flora strongly correlated with their metabolites. The findings of this study are expected to contribute to understanding the indications and contraindications for estrogen application in perimenopausal women and to aid in the development of appropriate therapeutic agents.
Importance: In this work, we employed 16S ribosomal RNA gene sequencing to analyze the gut microbes in stool samples. In addition, we conducted an ultra-high-performance liquid chromatography-tandem mass spectrometry-based metabolomics approach on gut tissue and serum obtained from rats with perimenopausal syndrome (PMS) and healthy controls. By characterizing the composition and metabolomic properties of gut microbes in PMS rats, we aim to enhance our understanding of their role in women's health, emphasizing the significance of regulating gut microbes in the context of menopausal women's well-being. We aim to provide a theoretical basis for the prevention and treatment of PMS in terms of gut microflora as well as metabolism.
{"title":"Integrated analysis of metabolome and microbiome in a rat model of perimenopausal syndrome.","authors":"Yanqiu Wei, Juanjuan Shi, Jianhua Wang, Zongyan Hu, Min Wang, Wen Wang, Xiujuan Cui","doi":"10.1128/msystems.00623-24","DOIUrl":"https://doi.org/10.1128/msystems.00623-24","url":null,"abstract":"<p><p>The objectives of this study are to examine the disparities in serum and intestinal tissue metabolites between a perimenopausal rat model and control rats and to analyze the diversity and functionality of intestinal microorganisms to determine the potential correlation between intestinal flora and metabolites. We established a rat model of perimenopausal syndrome (PMS) and performed an integrated analysis of metabolome and microbiome. Orthogonal partial least-squares discriminant analysis scores and replacement tests indicated distinct separations of anion and cation levels between serum and intestinal samples of the model and control groups. Furthermore, lipids and lipid-like molecules constituted the largest percentage of HMDB compounds in both serum and intestinal tissues, followed by organic acids and derivatives, and organoheterocyclic compounds, with other compounds showing significant variability. Moreover, analysis of diversity and functional enrichment of the intestinal microflora and correlation analysis with metabolites revealed significant variability in the composition of the intestinal flora between the normal control and perimenopausal groups, with these differentially expressed intestinal flora strongly correlated with their metabolites. The findings of this study are expected to contribute to understanding the indications and contraindications for estrogen application in perimenopausal women and to aid in the development of appropriate therapeutic agents.</p><p><strong>Importance: </strong>In this work, we employed 16S ribosomal RNA gene sequencing to analyze the gut microbes in stool samples. In addition, we conducted an ultra-high-performance liquid chromatography-tandem mass spectrometry-based metabolomics approach on gut tissue and serum obtained from rats with perimenopausal syndrome (PMS) and healthy controls. By characterizing the composition and metabolomic properties of gut microbes in PMS rats, we aim to enhance our understanding of their role in women's health, emphasizing the significance of regulating gut microbes in the context of menopausal women's well-being. We aim to provide a theoretical basis for the prevention and treatment of PMS in terms of gut microflora as well as metabolism.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470281","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}
Pub Date : 2024-10-18DOI: 10.1128/msystems.01297-24
Suet-Ying Kwan, Caroline M Sabotta, Lorenzo R Cruz, Matthew C Wong, Nadim J Ajami, Joseph B McCormick, Susan P Fisher-Hoch, Laura Beretta
{"title":"Correction for Kwan et al., \"Gut phageome in Mexican Americans: a population at high risk for metabolic dysfunction-associated steatotic liver disease and diabetes\".","authors":"Suet-Ying Kwan, Caroline M Sabotta, Lorenzo R Cruz, Matthew C Wong, Nadim J Ajami, Joseph B McCormick, Susan P Fisher-Hoch, Laura Beretta","doi":"10.1128/msystems.01297-24","DOIUrl":"https://doi.org/10.1128/msystems.01297-24","url":null,"abstract":"","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470275","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}
Pub Date : 2024-10-18DOI: 10.1128/msystems.01030-24
Lily Taub, Thomas H Hampton, Sharanya Sarkar, Georgia Doing, Samuel L Neff, Carson E Finger, Kiyoshi Ferreira Fukutani, Bruce A Stanton
E.PathDash facilitates re-analysis of gene expression data from pathogens clinically relevant to chronic respiratory diseases, including a total of 48 studies, 548 samples, and 404 unique treatment comparisons. The application enables users to assess broad biological stress responses at the KEGG pathway or gene ontology level and also provides data for individual genes. E.PathDash reduces the time required to gain access to data from multiple hours per data set to seconds. Users can download high-quality images such as volcano plots and boxplots, differential gene expression results, and raw count data, making it fully interoperable with other tools. Importantly, users can rapidly toggle between experimental comparisons and different studies of the same phenomenon, enabling them to judge the extent to which observed responses are reproducible. As a proof of principle, we invited two cystic fibrosis scientists to use the application to explore scientific questions relevant to their specific research areas. Reassuringly, pathway activation analysis recapitulated results reported in original publications, but it also yielded new insights into pathogen responses to changes in their environments, validating the utility of the application. All software and data are freely accessible, and the application is available at scangeo.dartmouth.edu/EPathDash.
Importance: Chronic respiratory illnesses impose a high disease burden on our communities and people with respiratory diseases are susceptible to robust bacterial infections from pathogens, including Pseudomonas aeruginosa and Staphylococcus aureus, that contribute to morbidity and mortality. Public gene expression datasets generated from these and other pathogens are abundantly available and an important resource for synthesizing existing pathogenic research, leading to interventions that improve patient outcomes. However, it can take many hours or weeks to render publicly available datasets usable; significant time and skills are needed to clean, standardize, and apply reproducible and robust bioinformatic pipelines to the data. Through collaboration with two microbiologists, we have shown that E.PathDash addresses this problem, enabling them to elucidate pathogen responses to a variety of over 400 experimental conditions and generate mechanistic hypotheses for cell-level behavior in response to disease-relevant exposures, all in a fraction of the time.
{"title":"E.PathDash, pathway activation analysis of publicly available pathogen gene expression data.","authors":"Lily Taub, Thomas H Hampton, Sharanya Sarkar, Georgia Doing, Samuel L Neff, Carson E Finger, Kiyoshi Ferreira Fukutani, Bruce A Stanton","doi":"10.1128/msystems.01030-24","DOIUrl":"https://doi.org/10.1128/msystems.01030-24","url":null,"abstract":"<p><p>E.PathDash facilitates re-analysis of gene expression data from pathogens clinically relevant to chronic respiratory diseases, including a total of 48 studies, 548 samples, and 404 unique treatment comparisons. The application enables users to assess broad biological stress responses at the KEGG pathway or gene ontology level and also provides data for individual genes. E.PathDash reduces the time required to gain access to data from multiple hours per data set to seconds. Users can download high-quality images such as volcano plots and boxplots, differential gene expression results, and raw count data, making it fully interoperable with other tools. Importantly, users can rapidly toggle between experimental comparisons and different studies of the same phenomenon, enabling them to judge the extent to which observed responses are reproducible. As a proof of principle, we invited two cystic fibrosis scientists to use the application to explore scientific questions relevant to their specific research areas. Reassuringly, pathway activation analysis recapitulated results reported in original publications, but it also yielded new insights into pathogen responses to changes in their environments, validating the utility of the application. All software and data are freely accessible, and the application is available at scangeo.dartmouth.edu/EPathDash.</p><p><strong>Importance: </strong>Chronic respiratory illnesses impose a high disease burden on our communities and people with respiratory diseases are susceptible to robust bacterial infections from pathogens, including <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i>, that contribute to morbidity and mortality. Public gene expression datasets generated from these and other pathogens are abundantly available and an important resource for synthesizing existing pathogenic research, leading to interventions that improve patient outcomes. However, it can take many hours or weeks to render publicly available datasets usable; significant time and skills are needed to clean, standardize, and apply reproducible and robust bioinformatic pipelines to the data. Through collaboration with two microbiologists, we have shown that E.PathDash addresses this problem, enabling them to elucidate pathogen responses to a variety of over 400 experimental conditions and generate mechanistic hypotheses for cell-level behavior in response to disease-relevant exposures, all in a fraction of the time.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470278","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}
Gut microbiota and associated metabolites have been linked to breast carcinogenesis. Evidences demonstrate blood microbiota primarily originates from the gut and may act as a biomarker for breast cancer. We aimed to characterize the microbiota-gut microbial metabolites cross-talk in blood and develop a composite diagnostic panel for breast cancer. We performed 16S rRNA gene sequencing and metabolomics profiling on blood samples from 107 breast cancer cases and 107 age-paired controls. We found that the alpha diversity of the blood microbiota was decreased in breast cancer compared to controls. There were significantly different profiles of microbiota and gut microbial metabolites in blood between these two groups, with nine bacterial genera and four gut microbial metabolites increased in patients, while thirty-nine bacterial genera and two gut microbial metabolites increased in controls. Some breast cancer-associated gut microbial metabolites were linked to differential blood microbiota, and a composite microbiota-metabolite diagnostic panel was further developed with an area under the curve of 0.963 for breast cancer. This study underscored the pivotal role of microbiota and gut microbial metabolites in blood and their interactions for breast carcinogenesis, as well as the potential of a composite diagnostic panel as a non-invasive biomarker for breast cancer.IMPORTANCEOur integrated analysis demonstrated altered profiles of microbiota and gut microbial metabolites in blood for breast cancer patients. The extensive correlation between microbiota and gut microbial metabolites in blood assisted the understanding of the pathogenesis of breast cancer. The good performance of a composite microbiota-gut microbial metabolites panel in blood suggested a non-invasive approach for breast cancer detection and a novel strategy for better diagnosis and prevention of breast cancer in the future.
{"title":"Integrated analysis of microbiota and gut microbial metabolites in blood for breast cancer.","authors":"Yu Peng, Jiale Gu, Fubin Liu, Peng Wang, Xixuan Wang, Changyu Si, Jianxiao Gong, Huijun Zhou, Ailing Qin, Fangfang Song","doi":"10.1128/msystems.00643-24","DOIUrl":"https://doi.org/10.1128/msystems.00643-24","url":null,"abstract":"<p><p>Gut microbiota and associated metabolites have been linked to breast carcinogenesis. Evidences demonstrate blood microbiota primarily originates from the gut and may act as a biomarker for breast cancer. We aimed to characterize the microbiota-gut microbial metabolites cross-talk in blood and develop a composite diagnostic panel for breast cancer. We performed 16S rRNA gene sequencing and metabolomics profiling on blood samples from 107 breast cancer cases and 107 age-paired controls. We found that the alpha diversity of the blood microbiota was decreased in breast cancer compared to controls. There were significantly different profiles of microbiota and gut microbial metabolites in blood between these two groups, with nine bacterial genera and four gut microbial metabolites increased in patients, while thirty-nine bacterial genera and two gut microbial metabolites increased in controls. Some breast cancer-associated gut microbial metabolites were linked to differential blood microbiota, and a composite microbiota-metabolite diagnostic panel was further developed with an area under the curve of 0.963 for breast cancer. This study underscored the pivotal role of microbiota and gut microbial metabolites in blood and their interactions for breast carcinogenesis, as well as the potential of a composite diagnostic panel as a non-invasive biomarker for breast cancer.IMPORTANCEOur integrated analysis demonstrated altered profiles of microbiota and gut microbial metabolites in blood for breast cancer patients. The extensive correlation between microbiota and gut microbial metabolites in blood assisted the understanding of the pathogenesis of breast cancer. The good performance of a composite microbiota-gut microbial metabolites panel in blood suggested a non-invasive approach for breast cancer detection and a novel strategy for better diagnosis and prevention of breast cancer in the future.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470282","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}