mSystems最新文献

{"title":"Microbial genotoxin-elicited host DNA mutations related to mitochondrial dysfunction, a momentous contributor for colorectal carcinogenesis.","authors":"Xue Yang, Yumeng Gan, Yuting Zhang, Zhongjian Liu, Jiawei Geng, Wenxue Wang","doi":"10.1128/msystems.00887-24","DOIUrl":"10.1128/msystems.00887-24","url":null,"abstract":"<p><p>Gut microbe dysbiosis increases repetitive inflammatory responses, leading to an increase in the incidence of colorectal cancer. Recent studies have revealed that specific microbial species directly instigate mutations in the host nucleus DNA, thereby accelerating the progression of colorectal cancer. Given the well-established role of mitochondrial dysfunction in promoting colorectal cancer, it is reasonable to postulate that gut microbes may induce mitochondrial gene mutations, thereby inducing mitochondrial dysfunction. In this review, we focus on gut microbial genotoxins and their known and potential targets in mitochondrial genes. Consequently, we propose that targeted disruption of genotoxin transport pathways may effectively reduce the rate of mitochondrial gene mutations and yield substantial benefits for the prevention of colorectal carcinogenesis.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomics and synthetic community experiments uncover the key metabolic roles of acetic acid bacteria in sourdough starter microbiomes","authors":"H. B. RappaportNimshika P. J. SenewiratneSarah K. LucasBenjamin E. WolfeAngela M. Oliverio1Department of Biology, Syracuse University, Syracuse, New York, USA2Department of Biology, Tufts University, Medford, Massachusetts, USADaniel Garrido","doi":"10.1128/msystems.00537-24","DOIUrl":"https://doi.org/10.1128/msystems.00537-24","url":null,"abstract":"mSystems, Ahead of Print. <br/>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254205","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":"Demographic and zoological drivers of infectome diversity in companion cats with ascites.","authors":"Yankuo Sun, Jiabao Xing, Sijia Xu, Yue Li, Jianhao Zhong, Han Gao, Song Cheng, Jun Dong, Tianyou Zhang, Gang Lu, Guy Baele, Guihong Zhang","doi":"10.1128/msystems.00636-24","DOIUrl":"10.1128/msystems.00636-24","url":null,"abstract":"<p><p>Cats (<i>Felidae</i>) have become an integral part of many households. However, our understanding of the full spectrum of pathogens affecting cats (referred to as the infectome) is limited, mainly due to the inadequacy of commonly used diagnostic tools in capturing the complete diversity of potential pathogens and the prevalence of pathogen co-infections. In this study, we employed a meta-transcriptomic approach to simultaneously characterize the infectome contributing to different disease syndromes and to investigate spatial, demographic, and ecological factors influencing pathogen diversity and community composition in a cohort of 27 hospitalized cats and seven stray cats. We identified 15 species of pathogens, with <i>Candidatus Rickettsia tarasevichiae</i> and <i>Tritrichomonas foetus</i> representing potential spillover risks. Importantly, although most cases of ascites hyperplasia were explained by coinfection with multiple pathogens, we identified the potential novel clinical outcomes of <i>M. aubagnense</i> infection among cats. We demonstrated that the increase in infectome diversity can be explained by a variety of predictors including age growth, temperature increase, and a higher proportion of females, with age growth presenting the strongest effect. Fine-scale analysis indicated that a higher diversity of infectomes were harbored in young cats rather than adult ones. Our results demonstrated that most feline diseases are better explained by the presence of virus-bacteria or virus-virus coinfection. This study serves as a timely endorsement for clinical diagnosis by vets to consider the cause of a disease based on a panel of cryptical co-infecting pathogens rather than on individual infectious agents.</p><p><strong>Importance: </strong>Frequent studies reported the risks of cats as an intermediate host of zoonotic pathogens (e.g., SARS-CoV-2). Cats have a physically close interaction with their owners through activities like petting, kissing, and being licked on the cheek and hands. However, there are still limited studies that systematically investigate the infectome structure of cats. In this study, we employed a meta-transcriptomics approach to characterize 15 species of pathogens in cats, with <i>Candidatus Rickettsia tarasevichiae</i> first characterizing infection in diseased cats. Most feline diseases were better explained by the presence of virus-bacteria or virus-virus coinfection. The increase in infectome diversity could be influenced by a variety of predictors including age growth, temperature increase, and a higher proportion of females. A higher diversity of pathogens was harbored in young cats rather than adults. Importantly, we showed the value of linking the modern influx of meta-transcriptomics with comparative ecology and demography and of utilizing it to affirm that ecological and demographic variations impact the total infectome.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic analysis of antibiotic resistance genes and mobile genetic elements in eight strains of nontyphoid <i>Salmonella</i>.","authors":"Haibing Liu, Lijie Zheng, Huimin Fan, Ji Pang","doi":"10.1128/msystems.00586-24","DOIUrl":"10.1128/msystems.00586-24","url":null,"abstract":"<p><p>Nontyphoidal <i>Salmonella</i> (NTS) is the main etiological agent of human nontyphoidal salmonellosis. The aim of this study was to analyze the epidemiological characteristics and horizontal transfer mechanisms of antimicrobial resistance (AMR) genes from eight strains of NTS detected in Zhenjiang City, Jiangsu Province, China. Fecal samples from outpatients with food-borne diarrhea were collected in 2022. The NTS isolates were identified, and their susceptibility was tested with the Vitek 2 Compact system. The genomes of the NTS isolates were sequenced with the Illumina NovaSeq platform and Oxford Nanopore Technologies platform. The AMR genes and mobile genetic elements (MGEs) were predicted with the relevant open access resources. Eight strains of NTS were isolated from 153 specimens, and <i>Salmonella</i> Typhimurium ST19 was the most prevalent serotype. The AMR gene with the highest detection rate was AAC(6<i>'</i>)-Iaa (10.5%) followed by TEM-1 (7.9%), sul2 (6.6%), and tet(A) (5.3%). Eleven MGEs carrying 34 AMR genes were identified on the chromosomes of 3 of the 8 NTS, including 3 resistance islands, 6 composite transposons (Tns), and 2 integrons. Eighteen plasmids carrying 40 AMR genes were detected in the 8 NTS strains, including 6 mobilizable plasmids, 3 conjugative plasmids, and 9 nontransferable plasmids, 7 of which carried 10 composite Tns and 3 integrons. This study provided a theoretical basis, from a genetic perspective, for the prevention and control of NTS resistance in Zhenjiang City.</p><p><strong>Importance: </strong>Human nontyphoidal salmonellosis is one of the common causes of bacterial food-borne illnesses, with significant social and economic impacts, especially those caused by invasive multidrug-resistant nontyphoidal <i>Salmonella</i>, which entails high morbidity and mortality. Antimicrobial resistance is mainly mediated by drug resistance genes, and mobile genetic elements play key roles in the capture, accumulation, and dissemination of antimicrobial resistance genes. Therefore, it is necessary to study the epidemiological characteristics and horizontal transfer mechanisms of antimicrobial resistance genes of nontyphoidal <i>Salmonella</i> to prevent the spread of multidrug-resistant nontyphoidal <i>Salmonella</i>.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential genes for <i>Haemophilus parainfluenzae</i> survival and biofilm growth.","authors":"Thais H de Palma, Chris Powers, Morgan J McPartland, Jessica Mark Welch, Matthew Ramsey","doi":"10.1128/msystems.00674-24","DOIUrl":"10.1128/msystems.00674-24","url":null,"abstract":"<p><p><i>Haemophilus parainfluenzae</i> (<i>Hp</i>) is a Gram-negative, highly prevalent, and abundant commensal in the human oral cavity, and an infrequent extraoral opportunistic pathogen. <i>Hp</i> occupies multiple niches in the oral cavity, including the supragingival plaque biofilm. Little is known about how <i>Hp</i> interacts with its neighbors in healthy biofilms nor its mechanisms of pathogenesis as an opportunistic pathogen. To address this, we identified the essential genome and conditionally essential genes in <i>in vitro</i> biofilms aerobically and anaerobically. Using transposon insertion sequencing (TnSeq) with a highly saturated <i>mariner</i> transposon library in two strains, the ATCC33392 type-strain (<i>Hp</i> 392) and oral isolate EL1 (<i>Hp</i> EL1), we show that the essential genomes of <i>Hp</i> 392 and <i>Hp</i> EL1 are composed of 395 (20%) and 384 (19%) genes, respectively. The core essential genome, consisting of 341 (17%) essential genes conserved between both strains, was composed of genes associated with genetic information processing, carbohydrate, protein, and energy metabolism. We also identified conditionally essential genes for aerobic and anaerobic biofilm growth, which were associated with carbohydrate and energy metabolism in both strains. RNAseq analysis determined that most genes upregulated during anaerobic growth are not essential for <i>Hp</i> 392 anaerobic survival. The completion of this library and analysis under these conditions gives us a foundational insight into the basic biology of <i>H. parainfluenzae</i> in differing oxygen conditions, similar to its <i>in vivo</i> habitat. This library presents a valuable tool for investigation into conditionally essential genes for an organism that lives in close contact with many microbial species in the human oral habitat.IMPORTANCE<i>Haemophilus parainfluenzae</i> is a highly abundant human commensal microbe, present in most healthy individuals where it colonizes the mouth. <i>H. parainfluenzae</i> correlates with good oral health and may play a role in preservation of healthy host status. Also, <i>H. parainfluenzae</i> can cause opportunistic infections outside of the oral cavity. To date, little is known about how <i>H. parainfluenzae</i> colonizes the human host, despite being such a frequent and abundant part of our human microbiome. Here, we demonstrate the creation and use of a powerful tool, a TnSeq library, used to identify genes necessary for both the outright growth of this organism and also genes conditionally essential for growth in varying oxygen status which it can encounter in the human host. This tool and these data serve as a foundation for further study of this relatively unknown organism that may play a role in preserving human health.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic requirements for uropathogenic E. coli proliferation in the bladder cell infection cycle","authors":"Daniel G. MediatiTamika A. BlairAriana CostasLeigh G. MonahanBill SöderströmIan G. CharlesIain G. Duggin1Australian Institute for Microbiology and Infection, University of Technology Sydney, Ultimo, Australia2Institut Cochin, INSERM U1016, Université de Paris, Paris, France3Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom4Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, United KingdomJoshua E. Elias","doi":"10.1128/msystems.00387-24","DOIUrl":"https://doi.org/10.1128/msystems.00387-24","url":null,"abstract":"mSystems, Ahead of Print. <br/>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254208","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":"Whole-genome sequencing for antimicrobial surveillance: species-specific quality thresholds and data evaluation from the network of the European Union Reference Laboratory for Antimicrobial Resistance genomic proficiency tests of 2021 and 2022.","authors":"Lauge Holm Sørensen, Susanne Karlsmose Pedersen, Jacob Dyring Jensen, Niamh Lacy-Roberts, Athina Andrea, Michael S M Brouwer, Kees T Veldman, Yan Lou, Maria Hoffmann, Rene S Hendriksen","doi":"10.1128/msystems.00160-24","DOIUrl":"10.1128/msystems.00160-24","url":null,"abstract":"<p><p>As antimicrobial resistance (AMR) surveillance shifts to genomics, ensuring the quality of whole-genome sequencing (WGS) data produced across laboratories is critical. Participation in genomic proficiency tests (GPTs) not only increases individual laboratories' WGS capacity but also provides a unique opportunity to improve species-specific thresholds for WGS quality control (QC) by repeated resequencing of distinct isolates. Here, we present the results of the EU Reference Laboratory for Antimicrobial Resistance (EURL-AR) network GPTs of 2021 and 2022, which included 25 EU national reference laboratories (NLRs). A total of 392 genomes from 12 AMR-bacteria were evaluated based on WGS QC metrics. Two percent (<i>n</i> = 9) of the data were excluded, due to contamination, and 11% (<i>n</i> = 41) of the remaining genomes were identified as outliers in at least one QC metric and excluded from computation of the adjusted QC thresholds (AQT). Two QC metric correlation groups were identified through linear regression. Eight percent (<i>n</i> = 28) of the submitted genomes, from 11 laboratories, failed one or more of the AQTs. However, only three laboratories (12%) were identified as underperformers, failing across AQTs for uncorrelated QC metrics in at least two genomes. Finally, new species-specific thresholds for \"N50\" and \"number of contigs > 200 bp\" are presented for guidance in routine laboratory QC. The continued participation of NRLs in GPTs will reveal WGS workflow flaws and improve AMR surveillance data. GPT data will continue to contribute to the development of reliable species-specific thresholds for routine WGS QC, standardizing sequencing data QC and ensure inter- and intranational laboratory comparability.IMPORTANCEIllumina next-generation sequencing is an integral part of antimicrobial resistance (AMR) surveillance and the most widely used whole-genome sequencing (WGS) platform. The high-throughput, relative low-cost, high discriminatory power, and rapid turnaround time of WGS compared to classical biochemical methods means the technology will likely remain a fundamental tool in AMR surveillance and public health. In this study, we present the current level of WGS capacity among national reference laboratories in the EU Reference Laboratory for AMR network, summarizing applied methodology and statistically evaluating the quality of the obtained sequence data. These findings provide the basis for setting new and revised thresholds for quality metrics used in routine WGS, which have previously been arbitrarily defined. In addition, underperforming participants are identified and encouraged to evaluate their workflows to produce reliable results.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ruminal microbial metagenomes and host transcriptomes shed light on individual variability in the growth rate of lambs before weaning: the regulated mechanism and potential long-term effect on the host.","authors":"Fan Hu, Yan Cheng, Bing Fan, Wei Li, Bingsen Ye, Zhiwu Wu, Zhiliang Tan, Zhixiong He","doi":"10.1128/msystems.00873-24","DOIUrl":"10.1128/msystems.00873-24","url":null,"abstract":"<p><p>Weaning weight is a reflection of management during the breastfeeding phase and will influence animal performance in subsequent phases, considered important indicators within production systems. The aims of this study were as follows: (i) to investigate variability in the growth rate among individual lambs from ewes rearing single or twin lambs fed with two different diets and (ii) to explore the molecular mechanisms regulating the growth rate and the potential long-term effects on the host. No significant change in lamb average daily gain (ADG) was observed in litter size and diet treatment, and there were large variations among individual lambs (ranging from 0.13 to 0.41 kg/day). Further analysis was conducted on serum amino acids, rumen fermentation characteristics, rumen metagenomics and transcriptome, and hepatic transcriptome of lambs with extremely high (HA; <i>n</i> = 6) and low (LA; <i>n</i> = 6) ADG. We observed significant increases in serum lysine, leucine, alanine, and phenylalanine in the HA group. The metagenome revealed that the HA group presented a higher rumen propionate molar proportion via increasing gene abundance in the succinate pathway for propionate synthesis. For the rumen transcriptome, higher expressed gene sets in the HA group were mainly related to rumen epithelial growth, including cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and adherens junction. For the liver transcriptome, the upregulated KEGG pathways in the HA group were primarily associated with fatty acid degradation, glyoxylate and dicarboxylate metabolism, cholesterol metabolism, and the immune system. This research suggests that preweaning lambs with high ADG may benefit from rumen development and enhanced liver metabolic and immune function.</p><p><strong>Importance: </strong>There is accumulating evidence indicating that the early-life rumen microbiome plays vital roles in rumen development and microbial fermentation, which subsequently affects the growth of young ruminants. The liver is also vital to regulate the metabolism and distribution of nutrients. Our results demonstrate that lambs with high average daily gain (ADG) enhanced microbial volatile fatty acid (VFA) metabolism toward rumen propionate and serum amino acid (AA) production to support host growth. The study highlights that high ADG in the preweaning period is beneficial for the rumen development and liver energy metabolism, leading to better growth later in life. Overall, this study explores the molecular mechanisms regulating the growth rate and the potential long-term effects of increased growth rate on the host metabolism, providing fundamental knowledge about nutrient manipulation in pre-weaning.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterial effect of phage cocktails and phage-antibiotic synergy against pathogenic <i>Klebsiella pneumoniae</i>.","authors":"Mengshi Zhao, Hongru Li, Dehao Gan, Mengzhu Wang, Hui Deng, Qiu E Yang","doi":"10.1128/msystems.00607-24","DOIUrl":"10.1128/msystems.00607-24","url":null,"abstract":"<p><p>The global rise of antibiotic resistance has renewed interest in phage therapy, as an alternative to antibiotics to eliminate multidrug-resistant (MDR) bacterial pathogens. However, optimizing the broad-spectrum efficacy of phage therapy remains a challenge. In this study, we addressed this issue by employing strategies to improve antimicrobial efficacy of phage therapy against MDR <i>Klebsiella pneumoniae</i> strains, which are notorious for their resistance to conventional antibiotics. This includes the selection of broad host range phages, optimization of phage formulation, and combinations with last-resort antibiotics. Our findings unveil that having a broad host range was a dominant trait of isolated phages, and increasing phage numbers in combination with antibiotics significantly enhanced the suppression of bacterial growth. The decreased incidence of bacterial infection was explained by a reduction in pathogen density and emergence of bacterial resistance. Furthermore, phage-antibiotic synergy (PAS) demonstrated considerable broad-spectrum antibacterial potential against different clades of clinical MDR <i>K. pneumoniae</i> pathogens. The improved treatment outcomes of optimized PAS were also evident in a murine model, where mice receiving optimized PAS therapy demonstrated a reduced bacterial burden in mouse tissues. Taken together, these findings offer an important development in optimizing PAS therapy and its efficacy in the elimination of MDR <i>K. pneumoniae</i> pathogens.</p><p><strong>Importance: </strong>The worldwide spread of antimicrobial resistance (AMR) has posed a great challenge to global public health. Phage therapy has become a promising alternative against difficult-to-treat pathogens. One important goal of this study was to optimize the therapeutic efficiency of phage-antibiotic combinations, known as phage-antibiotic synergy (PAS). Through comprehensive analysis of the phenotypic and genotypic characteristics of a large number of CRKp-specific phages, we developed a systematic model for phage cocktail combinations. Crucially, our finding demonstrated that PAS treatments not only enhance the bactericidal effects of colistin and tigecycline against multidrug-resistant (MDR) <i>K. pneumoniae</i> strains in <i>in vitro</i> and <i>in vivo</i> context but also provide a robust response when antibiotics fail. Overall, the optimized PAS therapy demonstrates considerable potential in combating diverse <i>K. pneumoniae</i> pathogens, highlighting its relevance as a strategy to mitigate antibiotic resistance threats effectively.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut dysbiosis contributes to the development of Budd-Chiari syndrome through immune imbalance.","authors":"Qinwei Lu, Rongtao Zhu, Lin Zhou, Ruifang Zhang, Zhen Li, Peng Xu, Zhiwei Wang, Gang Wu, Jianzhuang Ren, Dechao Jiao, Yan Song, Jian Li, Weijie Wang, Ruopeng Liang, Xiuxian Ma, Yuling Sun","doi":"10.1128/msystems.00794-24","DOIUrl":"10.1128/msystems.00794-24","url":null,"abstract":"<p><p>Budd-Chiari syndrome (B-CS) is a rare and lethal condition characterized by hepatic venous outflow tract blockage. Gut microbiota has been linked to numerous hepatic disorders, but its significance in B-CS pathogenesis is uncertain. First, we performed a case-control study (<i>N</i>_case = 140, <i>N</i>_control = 63) to compare the fecal microbiota of B-CS and healthy individuals by metagenomics sequencing. B-CS patients' gut microbial composition and activity changed significantly, with a different metagenomic makeup, increased potentially pathogenic bacteria, including <i>Prevotella</i>, and disease-linked microbial function. Imbalanced cytokines in patients were demonstrated to be associated with gut dysbiosis, which led us to suspect that B-CS is associated with gut microbiota and immune dysregulation. Next, 16S ribosomal DNA sequencing on fecal microbiota transplantation (FMT) mice models examined the link between gut dysbiosis and B-CS. FMT models showed damaged liver tissues, posterior inferior vena cava, and increased <i>Prevotella</i> in the disturbed gut microbiota of FMT mice. Notably, B-CS-FMT impaired the morphological structure of colonic tissues and increased intestinal permeability. Furthermore, a significant increase of the same cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, IL-17F, and IL-13) and endotoxin levels in B-CS-FMT mice were observed. Our study suggested that gut microbial dysbiosis may cause B-CS through immunological dysregulation.</p><p><strong>Importance: </strong>This study revealed that gut microbial dysbiosis may cause Budd-Chiari syndrome (B-CS). Gut dysbiosis enhanced intestinal permeability, and toxic metabolites and imbalanced cytokines activated the immune system. Consequently, the escalation of causative factors led to their concentration in the portal vein, thereby compromising both the liver parenchyma and outflow tract. Therefore, we proposed that gut microbial dysbiosis induced immune imbalance by chronic systemic inflammation, which contributed to the B-CS development. Furthermore, <i>Prevotella</i> may mediate inflammation development and immune imbalance, showing potential in B-CS pathogenesis.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018071","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}