Microbiome最新文献

{"title":"Dietary emulsifier carboxymethylcellulose-induced gut dysbiosis and SCFA reduction aggravate acute pancreatitis through classical monocyte activation.","authors":"Yongpu Feng, Wenjin Chen, Jiayu Chen, Fengyuan Sun, Fanyang Kong, Lei Li, Yating Zhao, Shouxin Wu, Zhaoshen Li, Yiqi Du, Xiangyu Kong","doi":"10.1186/s40168-025-02074-1","DOIUrl":"10.1186/s40168-025-02074-1","url":null,"abstract":"<p><strong>Objective: </strong>Carboxymethylcellulose (CMC), one of the most common emulsifiers used in the food industry, has been reported to promote chronic inflammatory diseases, but its impact on acute inflammatory diseases, e.g., acute pancreatitis (AP), remains unclear. This study investigates the detrimental effects of CMC on AP and the potential for mitigation through Akkermansia muciniphila or butyrate supplementation.</p><p><strong>Design: </strong>C57BL/6 mice were given pure water or CMC solution (1%) for 4 weeks and then subjected to caerulein-induced AP. The pancreas, colon, and blood were sampled for molecular and immune parameters associated with AP severity. Gut microbiota composition was assessed using 16S rRNA gene amplicon sequencing. Fecal microbiota transplantation (FMT) was used to illustrate gut microbiota's role in mediating the effects of CMC on host mice. Additional investigations included single-cell RNA sequencing, monocytes-specific C/EBPδ knockdown, LPS blocking, fecal short-chain fatty acids (SCFAs) quantification, and Akkermansia muciniphila or butyrate supplementation. Finally, the gut microbiota of AP patients with different severity was analyzed.</p><p><strong>Results: </strong>CMC exacerbated AP with gut dysbiosis. FMT from CMC-fed mice transferred such adverse effects to recipient mice, while single-cell analysis showed an increase in classical monocytes in blood. LPS-stimulated C/EBPδ, caused by an impaired gut barrier, drives monocytes towards classical phenotype. LPS antagonist (eritoran), Akkermansia muciniphila or butyrate supplementation ameliorates CMC-induced AP exacerbation. Fecal Akkermansia muciniphila abundance was negatively correlated with AP severity in patients.</p><p><strong>Conclusions: </strong>This study reveals the detrimental impact of CMC on AP due to gut dysbiosis, with Akkermansia muciniphila or butyrate offering potential therapeutic avenues for counteracting CMC-induced AP exacerbation. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"83"},"PeriodicalIF":13.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metagenomic signatures of extraintestinal bacterial infection in the febrile term infant gut microbiome.","authors":"Anna L DeVeaux, Carla Hall-Moore, Nurmohammad Shaikh, Meghan Wallace, Carey-Ann D Burnham, David Schnadower, Nathan Kuppermann, Prashant Mahajan, Octavio Ramilo, Phillip I Tarr, Gautam Dantas, Drew J Schwartz","doi":"10.1186/s40168-025-02079-w","DOIUrl":"10.1186/s40168-025-02079-w","url":null,"abstract":"<p><strong>Background: </strong>Extraintestinal bacterial infections (EBIs), e.g., urinary tract infection, bacteremia, and meningitis, occur in approximately 10% of febrile infants younger than 60 days. Although many EBI-causing species commonly reside in the infant gut, proof that the digestive system is a pre-infection habitat remains unestablished.</p><p><strong>Results: </strong>We studied a cohort of febrile term infants < 60 days old who presented to one of thirteen US emergency departments in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Forty EBI cases and 74 febrile controls matched for age, sex, and race without documented EBIs were selected for analysis. Shotgun sequencing was performed of the gut microbiome and of strains cultured from the gut and extraintestinal site(s) of EBI cases, including blood, urine, and/or cerebrospinal fluid. Using a combination of EBI isolate genomics and fecal metagenomics, we detected an intestinal strain presumptively isogenic to the EBI pathogen (> 99.999% average nucleotide identity) in 63% of infants with EBIs. Although there was no difference in gut microbiome diversity between cases and controls, we observed significantly increased Escherichia coli relative abundance in the gut microbiome of infants with EBIs caused by E. coli. Infants with E. coli infections who were colonized by the putatively isogenic pathogen strain had significantly higher E. coli phylogroup B2 abundance in their gut, and their microbiome was more likely to contain virulence factor loci associated with adherence, exotoxin production, and nutritional/metabolic function.</p><p><strong>Conclusions: </strong>The intestine plausibly serves as a reservoir for EBI pathogens in a subset of febrile term infants, prompting consideration of new opportunities for surveillance and EBI prevention among colonized, pre-symptomatic infants. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"82"},"PeriodicalIF":13.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal dynamics and metagenomics of phosphorothioate epigenomes in the human gut microbiome.","authors":"Shane R Byrne, Michael S DeMott, Yifeng Yuan, Farzan Ghanegolmohammadi, Stefanie Kaiser, James G Fox, Eric J Alm, Peter C Dedon","doi":"10.1186/s40168-025-02071-4","DOIUrl":"10.1186/s40168-025-02071-4","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic regulation of gene expression and host defense is well established in microbial communities, with dozens of DNA modifications comprising the epigenomes of prokaryotes and bacteriophage. Phosphorothioation (PT) of DNA, in which a chemically reactive sulfur atom replaces a non-bridging oxygen in the sugar-phosphate backbone, is catalyzed by dnd and ssp gene families widespread in bacteria and archaea. However, little is known about the role of PTs or other microbial epigenetic modifications in the human microbiome. Here we optimized and applied fecal DNA extraction, mass spectrometric, and metagenomics technologies to characterize the landscape and temporal dynamics of gut microbes possessing PT modifications.</p><p><strong>Results: </strong>Exploiting the nuclease-resistance of PTs, mass spectrometric analysis of limit digests of PT-containing DNA reveals PT dinucleotides as part of genomic consensus sequences, with 16 possible dinucleotide combinations. Analysis of mouse fecal DNA revealed a highly uniform spectrum of 11 PT dinucleotides in all littermates, with PTs estimated to occur in 5-10% of gut microbes. Though at similar levels, PT dinucleotides in fecal DNA from 11 healthy humans possessed signature combinations and levels of individual PTs. Comparison with a widely distributed microbial epigenetic mark, m⁶dA, suggested temporal dynamics consistent with expectations for gut microbial communities based on Taylor's Power Law. Application of PT-seq for site-specific metagenomic analysis of PT-containing bacteria in one fecal donor revealed the larger consensus sequences for the PT dinucleotides in Bacteroidota, Bacillota (formerly Firmicutes), Actinomycetota (formerly Actinobacteria), and Pseudomonadota (formerly Proteobacteria), which differed from unbiased metagenomics and suggested that the abundance of PT-containing bacteria did not simply mirror the spectrum of gut bacteria. PT-seq further revealed low abundance PT sites not detected as dinucleotides by mass spectrometry, attesting to the complementarity of the technologies. Video Abstract CONCLUSIONS: The results of our studies provide a benchmark for understanding the behavior of an abundant and chemically reactive epigenetic mark in the human gut microbiome, with implications for inflammatory conditions of the gut.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"81"},"PeriodicalIF":13.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variety-dependent seed endophytic bacteria enhance stress tolerance to and bioaccumulation of ciprofloxacin in choy sum (Brassica parachinensis).","authors":"Yi-Ze Wang, Hai-Ming Zhao, Xian-Pei Huang, Yu Zhang, Jin-Cheng Ye, Nai-Xian Feng, Yan-Wen Li, Bai-Lin Liu, Quan-Ying Cai, Lei Xiang, Ce-Hui Mo, Qing X Li","doi":"10.1186/s40168-025-02073-2","DOIUrl":"10.1186/s40168-025-02073-2","url":null,"abstract":"<p><strong>Background: </strong>Accumulation of antibiotics in crops threatens human health. However, the mechanisms and effects of microorganisms on the uptake and accumulation of antibiotics in crops remain poorly understood. This study aimed to investigate the impact and underlying mechanisms of seed-borne microbiota in root on ciprofloxacin (CIP) accumulation in two choy sum varieties through amplicon sequencing, multiple statistical analyses, and subsequent validation of key bacteria via isolation and co-culturing with plants.</p><p><strong>Results: </strong>Bacillaceae (mainly Bacillus) was enriched specifically in the roots of CIP high-antibiotic-accumulating variety (HAV) via seed-based vertical transmission activated by the root exudate-derived maleic acid. The relative abundance of Bacillaceae was 9.2 to 27.7 times higher in roots of HAV relative to the low-antibiotic-accumulating variety (LAV). The enrichment of Bacillaceae facilitated a cooperative and beneficial bacterial community formed by the deterministic process. The community in HAV could not only stimulate antioxidase activities and decrease membrane lipid peroxidation via secreting indoleacetic acid and siderophore but also promote its biomass, especially the root length and biomass of HAV, thus greatly improving its tolerance to and absorption of CIP. The variety-specific plant-microbial interactions caused 1.6- to 3.2-fold higher CIP accumulation in shoots of HAV relative to LAV shoots.</p><p><strong>Conclusions: </strong>The findings highlight the crucial roles of the seed-borne microbiota in regulating the uptake and accumulation of antibiotics in crops, giving new understanding on the accumulation of organic pollutants in plants, with an emphasis on plant-microbial interactions Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"80"},"PeriodicalIF":13.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tunturi virus isolates and metagenome-assembled viral genomes provide insights into the virome of Acidobacteriota in Arctic tundra soils.","authors":"Tatiana Demina, Heli Marttila, Igor S Pessi, Minna K Männistö, Bas E Dutilh, Simon Roux, Jenni Hultman","doi":"10.1186/s40168-025-02053-6","DOIUrl":"10.1186/s40168-025-02053-6","url":null,"abstract":"<p><strong>Background: </strong>Arctic soils are climate-critical areas, where microorganisms play crucial roles in nutrient cycling processes. Acidobacteriota are phylogenetically and physiologically diverse bacteria that are abundant and active in Arctic tundra soils. Still, surprisingly little is known about acidobacterial viruses in general and those residing in the Arctic in particular. Here, we applied both culture-dependent and -independent methods to study the virome of Acidobacteriota in Arctic soils.</p><p><strong>Results: </strong>Five virus isolates, Tunturi 1-5, were obtained from Arctic tundra soils, Kilpisjärvi, Finland (69°N), using Tunturiibacter spp. strains originating from the same area as hosts. The new virus isolates have tailed particles with podo- (Tunturi 1, 2, 3), sipho- (Tunturi 4), or myovirus-like (Tunturi 5) morphologies. The dsDNA genomes of the viral isolates are 63-98 kbp long, except Tunturi 5, which is a jumbo phage with a 309-kbp genome. Tunturi 1 and Tunturi 2 share 88% overall nucleotide identity, while the other three are not related to one another. For over half of the open reading frames in Tunturi genomes, no functions could be predicted. To further assess the Acidobacteriota-associated viral diversity in Kilpisjärvi soils, bulk metagenomes from the same soils were explored and a total of 1881 viral operational taxonomic units (vOTUs) were bioinformatically predicted. Almost all vOTUs (98%) were assigned to the class Caudoviricetes. For 125 vOTUs, including five (near-)complete ones, Acidobacteriota hosts were predicted. Acidobacteriota-linked vOTUs were abundant across sites, especially in fens. Terriglobia-associated proviruses were observed in Kilpisjärvi soils, being related to proviruses from distant soils and other biomes. Approximately genus- or higher-level similarities were found between the Tunturi viruses, Kilpisjärvi vOTUs, and other soil vOTUs, suggesting some shared groups of Acidobacteriota viruses across soils.</p><p><strong>Conclusions: </strong>This study provides acidobacterial virus isolates as laboratory models for future research and adds insights into the diversity of viral communities associated with Acidobacteriota in tundra soils. Predicted virus-host links and viral gene functions suggest various interactions between viruses and their host microorganisms. Largely unknown sequences in the isolates and metagenome-assembled viral genomes highlight a need for more extensive sampling of Arctic soils to better understand viral functions and contributions to ecosystem-wide cycling processes in the Arctic. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"79"},"PeriodicalIF":13.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the female genital tract mycobiome in young South African women using metaproteomics.","authors":"Tamlyn K Gangiah, Arghavan Alisoltani, Matthys Potgieter, Liam Bell, Elizabeth Ross, Arash Iranzadeh, Zac McDonald, Imane Allali, Smritee Dabee, Shaun Barnabas, Jonathan M Blackburn, David L Tabb, Linda-Gail Bekker, Heather B Jaspan, Jo-Ann S Passmore, Nicola Mulder, Lindi Masson","doi":"10.1186/s40168-025-02066-1","DOIUrl":"10.1186/s40168-025-02066-1","url":null,"abstract":"<p><strong>Background: </strong>Female genital tract (FGT) diseases such as bacterial vaginosis (BV) and sexually transmitted infections are prevalent in South Africa, with young women being at an increased risk. Since imbalances in the FGT microbiome are associated with FGT diseases, it is vital to investigate the factors that influence FGT health. The mycobiome plays an important role in regulating mucosal health, especially when the bacterial component is disturbed. However, we have a limited understanding of the FGT mycobiome since many studies have focused on bacterial communities and have neglected low-abundance taxonomic groups, such as fungi. To reduce this knowledge deficit, we present the first large-scale metaproteomic study to define the taxonomic composition and potential functional processes of the FGT mycobiome in South African reproductive-age women.</p><p><strong>Results: </strong>We examined FGT fungal communities present in 123 women by collecting lateral vaginal wall swabs for liquid chromatography-tandem mass spectrometry. From this, 39 different fungal genera were identified, with Candida dominating the mycobiome (53.2% relative abundance). We observed changes in relative abundance at the protein, genus, and functional (gene ontology biological processes) level between BV states. In women with BV, Malassezia and Conidiobolus proteins were more abundant, while Candida proteins were less abundant compared to BV-negative women. Correspondingly, Nugent scores were negatively associated with total fungal protein abundance. The clinical variables, Nugent score, pro-inflammatory cytokines, chemokines, vaginal pH, Chlamydia trachomatis, and the presence of clue cells were associated with fungal community composition.</p><p><strong>Conclusions: </strong>The results of this study revealed the diversity of FGT fungal communities, setting the groundwork for understanding the FGT mycobiome. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"76"},"PeriodicalIF":13.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicrobeRX: a tool for enzymatic-reaction-based metabolite prediction in the gut microbiome.","authors":"Angel J Ruiz-Moreno, Ángela Del Castillo-Izquierdo, Isabel Tamargo-Rubio, Jingyuan Fu","doi":"10.1186/s40168-025-02070-5","DOIUrl":"10.1186/s40168-025-02070-5","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiome functions as a metabolic organ, producing numerous enzymes that influence host health; however, their substrates and metabolites remain largely unknown.</p><p><strong>Results: </strong>We present MicrobeRX, an enzyme-based metabolite prediction tool that employs 5487 human reactions and 4030 unique microbial reactions from 6286 genome-scale models, as well as 3650 drug metabolic reactions from the DrugBank database (v.5.1.12). MicrobeRX includes additional analysis modules for metabolite visualization and enzymatic and taxonomic analyses. When we applied MicrobeRX to 1083 orally administered drugs that have been approved in at least one jurisdiction at some point in time (DrugBank), it predicted metabolites with physicochemical properties and structures similar to metabolites found in biosamples (from MiMeDB). It also outperformed another existing metabolite prediction tool (BioTransformer 3.0) in terms of predictive potential, molecular diversity, reduction of redundant predictions, and enzyme annotation.</p><p><strong>Conclusions: </strong>Our analysis revealed both unique and overlapping metabolic capabilities in human and microbial metabolism and chemo- and taxa-specific microbial biotransformations. MicrobeRX bridges the genomic and chemical spaces of the gut microbiome, making it a valuable tool for unlocking the chemical potential of the gut microbiome in human health, the food and pharmaceutical industries, and environmental safety. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"78"},"PeriodicalIF":13.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global analysis of the metaplasmidome: ecological drivers and spread of antibiotic resistance genes across ecosystems.","authors":"Didier Debroas","doi":"10.1186/s40168-025-02062-5","DOIUrl":"10.1186/s40168-025-02062-5","url":null,"abstract":"<p><strong>Background: </strong>Plasmids act as vehicles for the rapid spread of antibiotic resistance genes (ARGs). However, few studies of the resistome at the community level distinguish between ARGs carried by mobile genetic elements and those carried by chromosomes, and these studies have been limited to a few ecosystems. This is the first study to focus on ARGs carried by the metaplasmidome on a global scale.</p><p><strong>Results: </strong>This study shows that only a small fraction of the plasmids reconstructed from 27 ecosystems representing 9 biomes are catalogued in public databases. The abundance of ARGs harboured by the metaplasmidome was significantly explained by bacterial richness. Few plasmids with or without ARGs were shared between ecosystems or biomes, suggesting that plasmid distribution on a global scale is mainly driven by ecology rather than geography. The network linking plasmids to their hosts shows that these mobile elements have thus been shared between bacteria across geographically distant environmental niches. However, certain plasmids carrying ARGs involved in human health were identified as being shared between multiple ecosystems and hosted by a wide variety of hosts. Some of these mobile elements, identified as keystone plasmids, were characterised by an enrichment in antibiotic resistance genes (ARGs) and CAS-CRISPR components which may explain their ecological success. The ARGs accounted for 9.2% of the recent horizontal transfers between bacteria and plasmids.</p><p><strong>Conclusions: </strong>By comprehensively analysing the plasmidome content of ecosystems, some key habitats have emerged as particularly important for monitoring the spread of ARGs in relation to human health. Of particular note is the potential for air to act as a vector for long-distance transport of ARGs and accessory genes across ecosystems and continents. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"77"},"PeriodicalIF":13.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term and long-term high-fat diet promote metabolic disorder through reprogramming mRNA m⁶A in white adipose tissue by gut microbiota.","authors":"Youhua Liu, Jiaqi Liu, Ruiti Ren, Zimeng Xin, Yaojun Luo, Yushi Chen, Chaoqun Huang, Yuxi Liu, Tongyudan Yang, Xinxia Wang","doi":"10.1186/s40168-025-02047-4","DOIUrl":"10.1186/s40168-025-02047-4","url":null,"abstract":"<p><strong>Background: </strong>Although short-term high-fat diet (S-HFD) and long-term high-fat diet (L-HFD) induce metabolic disorder, the underlying epigenetic mechanism is still unclear.</p><p><strong>Results: </strong>Here, we found that both 4 days of S-HFD and 10 weeks of L-HFD increased mRNA m⁶A level in epididymal white adipose tissue (eWAT) and impaired metabolic health. Interestingly, S-HFD activated transposable elements (TEs), especially endogenous retroviruses (ERVs) in eWAT, while L-HFD activated long interspersed elements (LINEs). Subsequently, we demonstrated that both S-HFD and L-HFD increased m⁶A level of Ehmt2 and decreased EHMT2 protein expression and H3K9me2 level, accounting for activation of ERVs and LINEs. Overexpression of EHMT2 in eWAT or inhibition of ERVs and LINEs by antiviral therapy improved metabolic health under HFD feeding. Notably, we found that both short-term and long-term HFD feeding increased Fimicutes/Bacteroidota ratio and decreased the gut microbiome health index. Fecal microbiota transplantation (FMT) experiments demonstrated that gut microbiota from S-HFD and L-HFD was responsible for increased m⁶A level in eWAT, resulting in glucose intolerance and insulin insensitivity. Furthermore, we identified that both S-HFD and L-HFD increased the abundance of the gut microbial metabolite homogentisic acid (HGA), and HGA level was positively correlated with unclassified_f__Lachnospiraceae which was both increased in S-HFD and L-HFD feeding mice. Administration of HGA increased the m⁶A level of Ehmt2 and decreased the EHMT2 protein expression and H3K9me2 level in eWAT, leading to metabolic disorder in mice.</p><p><strong>Conclusions: </strong>Together, this study reveals a novel mechanism that S-HFD and L-HFD induce metabolism disorder through gut microbiota-HGA-m⁶A-Ehmt2-ERV/LINE signaling. These findings may provide a novel insight for prevention and treatment of metabolism disorder upon short-term or long-term dietary fat intake. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"75"},"PeriodicalIF":13.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: The intestinal microbiome and metabolome discern disease severity in cytotoxic T-lymphocyte-associated protein 4 deficiency.","authors":"Prabha Chandrasekaran, Máté Krausz, Yu Han, Noriko Mitsuiki, Annemarie Gabrysch, Christina Nöltner, Michele Proietti, Theo Heller, Caroline Grou, Virginie Calderon, Poorani Subramanian, Drew R Jones, Yik Siu, Clayton Deming, Sean Conlan, Steven M Holland, Julia A Segre, Gulbu Uzel, Bodo Grimbacher, Emilia Liana Falcone","doi":"10.1186/s40168-025-02069-y","DOIUrl":"10.1186/s40168-025-02069-y","url":null,"abstract":"","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"74"},"PeriodicalIF":13.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}