{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:17:45Z","timestamp":1783606665050,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The microbiome of patients with hepatitis D virus (HDV) has yet to be characterized. This study aims to (1) characterize gut microbial composition in HDV, (2) determine its functional profile, (3) identify microbial species that contribute to changes in pathway expression, and (4) correlate the changes in the gut microbiome with clinical markers of disease severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cross-sectional analyses of 35 HDV-infected patients and 32 healthy controls (HCs) were performed. DNA and RNA were isolated from stool and sequenced by shotgun-sequencing. Microbial and functional profiles were compared between the HDV-cohort and HCs to identify disease-specific alterations to the gut microbiome. Clinical metadata were used to identify correlations with disease severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There were significant changes in the composition of the gut microbiome in HDV-infected patients as compared with HCs, spanning multiple bacterial phyla. Expression of 194 pathways was significantly increased in the HDV group. Pathways that were upregulated in the HDV cohort were related to amino acid and carbohydrate biosynthesis or involved important metabolic cofactors and carriers. Several microbial species, including\n                      <jats:italic>Bacteroides fragilis<\/jats:italic>\n                      ,\n                      <jats:italic>Cateibacterium mitsuokai<\/jats:italic>\n                      , and\n                      <jats:italic>Faecalibacterium prausnitzii<\/jats:italic>\n                      , were identified as contributing to the differentially expressed pathways. Four genera correlated with hepatic venous pressure gradient (HVPG).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>There are significant differences in microbial composition between HDV and HCs, several of which are found to be altered in other liver diseases. Upregulated pathways suggest a broader dysregulation of energy metabolism, even in early disease. These findings provide insight into pathways that may lead to liver disease progression in HDV.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1851892","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:34:12Z","timestamp":1783604052000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic hepatitis D infection is associated with distinguishing microbial and functional features in the gut microbiome"],"prefix":"10.3389","volume":"17","author":[{"given":"Meital A.","family":"Gewirtz","sequence":"first","affiliation":[{"name":"Translational Hepatology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health","place":["Bethesda, MD, United 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Microbiol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41564-022-01273-y","article-title":"Longitudinal multi\u2011omics analyses of the gut\u2013liver axis reveals metabolic dysregulation in hepatitis C infection and cirrhosis","volume":"8","author":"Ali","year":"2023","journal-title":"Nat. Microbiol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1038\/nmeth.3103","article-title":"Binning metagenomic contigs by coverage and composition","volume":"11","author":"Alneberg","year":"2014","journal-title":"Nat. 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Hepatol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e65088","DOI":"10.7554\/eLife.65088","article-title":"Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3","volume":"10","author":"Beghini","year":"2021","journal-title":"eLife"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"3137","DOI":"10.1093\/bioinformatics\/btx373","article-title":"FQC dashboard: integrates FastQC results into a web-based, interactive, and extensible FASTQ quality control tool","volume":"33","author":"Brown","year":"2017","journal-title":"Bioinformatics"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"D471","DOI":"10.1093\/nar\/gkv1164","article-title":"The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway\/genome databases","volume":"44","author":"Caspi","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1038\/s41467-019-09455-9","article-title":"A gut microbiome signature for cirrhosis due to nonalcoholic fatty liver disease","volume":"10","author":"Caussy","year":"2019","journal-title":"Nat. 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Microbiol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1016\/j.jcmgh.2023.01.004","article-title":"Gut microbiota\u2013derived glutamine attenuates liver ischemia\/reperfusion injury via macrophage metabolic reprogramming","volume":"15","author":"Lu","year":"2023","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e1009442","DOI":"10.1371\/journal.pcbi.1009442","article-title":"Multivariable association discovery in population-scale meta-omics studies","volume":"17","author":"Mallick","year":"2021","journal-title":"PLoS Comput. Biol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"4068","DOI":"10.1128\/IAI.02256-14","article-title":"Pathogenic bacterial species associated with endodontic infection evade innate immune control by disabling neutrophils","volume":"82","author":"Matsui","year":"2014","journal-title":"Infect. 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Sci."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1101\/gr.213959.116","article-title":"metaSPAdes: a new versatile metagenomic assembler","volume":"27","author":"Nurk","year":"2017","journal-title":"Genome Res."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"2864","DOI":"10.1038\/ismej.2017.126","article-title":"dRep: a tool for fast and accurate genomic comparisons that enables improved genome recovery from metagenomes through de-replication","volume":"11","author":"Olm","year":"2017","journal-title":"ISME J."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"104468","DOI":"10.1016\/j.bjid.2024.104468","article-title":"Dysregulation in the microbiota by HBV and HCV infection induces an altered cytokine profile in the pathobiome of infection","volume":"29","author":"Padilha","year":"2025","journal-title":"Braz. J. Infect. 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Microbiol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2155018","DOI":"10.1080\/19490976.2022.2155018","article-title":"Alterations in gut microbiome and metabolomics in chronic hepatitis B infection-associated liver disease and their impact on peripheral immune response","volume":"15","author":"Shen","year":"2023","journal-title":"Gut Microbes"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s40168-018-0541-1","article-title":"MetaWRAP\u2014a flexible pipeline for genome-resolved metagenomic data analysis","volume":"6","author":"Uritskiy","year":"2024","journal-title":"Microbiome"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41423-020-00592-6","article-title":"Gut microbiome, liver immunology, and liver diseases","volume":"18","author":"Wang","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1128\/CMR.00008-07","article-title":"Bacteroides: the good, the bad, and the nitty-gritty","volume":"20","author":"Wexler","year":"2007","journal-title":"Clin. Microbiol. 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