{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T02:21:03Z","timestamp":1776910863806,"version":"3.51.2"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"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. Public Health"],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to explore the potential causal relationship between the gut microbiota and\/or its metabolites and the progression of chronic hepatitis B (CHB).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>The gut microbiota was used as the exposure factor. The training set exposure data were obtained from the China Nucleotide Sequence Archive (CNSA). Genome-wide association study (GWAS) data from Asia were used as the outcome variables. Outcome data for both the training and validation sets were sourced from the GWAS Catalog database. A dual-sample Mendelian randomization approach was used to analyze the causal relationships, with the inverse variance-weighted method serving as the main analytical strategy. Sensitivity analysis was conducted to assess the robustness of Mendelian randomization analysis results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>In the training set database, analysis using the inverse variance-weighted method revealed a positive correlation between <jats:italic>Fusobacterium varium<\/jats:italic> and chronic hepatitis B [OR\u2009=\u20091.122, 95% CI (1.016, 1.240), <jats:italic>p<\/jats:italic>\u2009=\u20090.022]. Conversely, <jats:italic>Veillonella parvula<\/jats:italic> exhibited a negative correlation with chronic hepatitis B [OR\u2009=\u20090.917, 95% CI (0.852, 0.987), <jats:italic>p<\/jats:italic>\u2009=\u20090.021]. Sensitivity analysis revealed no evidence of pleiotropy and heterogeneity. No gut microbiota metabolites with a causal effect on chronic hepatitis B were identified. Additionally, no associations between the gut microbiota and the progression of chronic hepatitis B were found in the validation data from the European cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study suggests that <jats:italic>F. varium<\/jats:italic> may facilitate the progression of chronic hepatitis B, whereas <jats:italic>V. parvula<\/jats:italic> may impede it. No causal relationships between gut microbiota metabolites and chronic hepatitis B were established.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpubh.2024.1398254","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T05:15:16Z","timestamp":1721798116000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["A Mendelian randomization study investigating causal links between gut microbiota or metabolites and chronic hepatitis B"],"prefix":"10.3389","volume":"12","author":[{"given":"Tongjing","family":"Xing","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuequan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,24]]},"reference":[{"key":"ref1","year":""},{"key":"ref2","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/S2468-1253(18)30056-6","article-title":"Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study","volume":"3","year":"2018","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41577-021-00549-4","article-title":"Immunobiology and pathogenesis of hepatitis B virus infection","volume":"22","author":"Iannacone","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1053\/j.gastro.2015.11.050","article-title":"Hepatitis B virus-specific and global T-cell dysfunction in chronic hepatitis B[J]","volume":"150","author":"Park","year":"2016","journal-title":"Gastroenterology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1053\/j.gastro.2012.07.014","article-title":"Restored function of HBV-specific T cells after long-term effective therapy with nucleos(t)ide analogues","volume":"143","author":"Boni","year":"2012","journal-title":"Gastroenterology"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1016\/j.cell.2018.02.044","article-title":"The human gut microbiome: from association to modulation","volume":"172","author":"Schmidt","year":"2018","journal-title":"Cell"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.jcmgh.2015.04.003","article-title":"The gut microbiota and liver disease","volume":"1","author":"Llorente","year":"2015","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1073\/pnas.1424775112","article-title":"Age related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota","volume":"112","author":"Chou","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref9","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":"ref10","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13099-020-00391-4","article-title":"Potential role of intestinal microflora in disease progression among patients with different stages of hepatitis B","volume":"12","author":"Yang","year":"2020","journal-title":"Gut Pathog"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1007\/s00248-010-9801-8","article-title":"Intestinal microbiota was assessed in cirrhotic patients with hepatitis B virus infection. 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