{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:57:34Z","timestamp":1792195054514,"version":"4.4.0"},"reference-count":23,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T00:00:00Z","timestamp":1613260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AA24726, R01AA020703, U01 AA026939"],"award-info":[{"award-number":["R01 AA24726, R01AA020703, U01 AA026939"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Alcohol-related liver disease is one of the most prevalent types of chronic liver diseases globally. Alcohol-related liver disease begins with fatty liver, which further develops into hepatic inflammation, hepatocyte injury, and progresses to fibrosis and cirrhosis. Compositional changes of gut bacteria and fungi were found in patients with alcohol-related liver disease. However, the functional changes of fungi and correlations between fungi and bacteria have not been investigated. In this study, we first examined the functional capacity of fungi in patients with alcohol-related liver disease using shotgun metagenomics. Among 24 MetaCyc pathways contributed by fungi, superpathway of allantoin degradation in yeast was enriched in patients with alcoholic hepatitis. Furthermore, we compared the predictive power of bacteria versus fungi and found that bacteria performed better than fungi to separate patients with alcoholic hepatitis from non-alcoholic controls and patients with alcohol use disorder. Finally, we investigated the associations between the intestinal fungi and bacteria in alcoholic hepatitis patients. Positive association between fungi and bacteria was found between Cladosporium and Gemmiger, meanwhile negative association was found between Cryptococcus and Pseudomonas in alcoholic hepatitis patients.<\/jats:p>","DOI":"10.3390\/toxins13020143","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T10:01:05Z","timestamp":1613296865000},"page":"143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Fungi\u2013Bacteria Correlation in Alcoholic Hepatitis Patients"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3321-2339","authenticated-orcid":false,"given":"Bei","family":"Gao","sequence":"first","affiliation":[{"name":"School of Marine Sciences, Nanjing University of Information Science and Technology, Nanjing 210044, China"},{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Schnabl","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"Department of Medicine, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1042\/BCJ20160510","article-title":"Introduction to the Human Gut Microbiota","volume":"474","author":"Thursby","year":"2017","journal-title":"Biochem. J."},{"key":"ref_2","first-page":"147","article-title":"Alcoholic Liver Disease: Pathogenesis and Current Management","volume":"38","author":"Osna","year":"2017","journal-title":"Alcohol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1007\/BF02282340","article-title":"Small Bowel Bacterial Overgrowth in Patients with Alcoholic Cirrhosis","volume":"41","author":"Ledesma","year":"1996","journal-title":"Dig. Dis. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1785251","DOI":"10.1080\/19490976.2020.1785251","article-title":"Changes in the Fecal Bacterial Microbiota Associated with Disease Severity in Alcoholic Hepatitis Patients","volume":"12","author":"Lang","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/hep.30832","article-title":"Intestinal Fungal Dysbiosis and Systemic Immune Response to Fungi in Patients with Alcoholic Hepatitis","volume":"71","author":"Lang","year":"2020","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/nm.3871","article-title":"Activation of HIF-1\u03b1 and LL-37 by Commensal Bacteria Inhibits Candida Albicans Colonization","volume":"21","author":"Fan","year":"2015","journal-title":"Nat. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nature13995","article-title":"Human Gut Bacteroidetes Can Utilize Yeast Mannan through a Selfish Mechanism","volume":"517","author":"Cuskin","year":"2015","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e01011","DOI":"10.1128\/mBio.01011-14","article-title":"Saccharomyces Boulardii Administration Changes Gut Microbiota and Reduces Hepatic Steatosis, Low-Grade Inflammation, and Fat Mass in Obese and Type 2 Diabetic Db\/Db Mice","volume":"5","author":"Everard","year":"2014","journal-title":"mBio"},{"key":"ref_9","first-page":"91","article-title":"Allantoin Degradation by Saccharomyces Cerevisiae--a Model System for Gene Regulation and Metabolic Integration","volume":"56","author":"Cooper","year":"1984","journal-title":"Adv. Enzymol. Relat. Areas Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1002\/hep.31197","article-title":"Elevated Fructose and Uric Acid Through Aldose Reductase Contribute to Experimental and Human Alcoholic Liver Disease","volume":"72","author":"Wang","year":"2020","journal-title":"Hepatology"},{"key":"ref_11","first-page":"393","article-title":"Virulence factors in Pseudomonas aeruginosa: Mechanisms and modes of regulation","volume":"69","author":"Moissenet","year":"2011","journal-title":"Ann. Biol. Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrmicro.2015.6","article-title":"Cryptococcus: From Environmental Saprophyte to Global Pathogen","volume":"14","author":"May","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s11046-011-9494-7","article-title":"Pseudomonas Aeruginosa Inhibits the Growth of Cryptococcus Species","volume":"173","author":"Rella","year":"2012","journal-title":"Mycopathologia"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gao, B., Emami, A., Zhou, R., Lang, S., Duan, Y., Wang, Y., Jiang, L., Loomba, R., Brenner, D., and St\u00e4rkel, P. (2020). Functional Microbial Responses to Alcohol Abstinence in Patients with Alcohol Use Disorder. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00370"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1038\/nmeth.3589","article-title":"MetaPhlAn2 for Enhanced Metagenomic Taxonomic Profiling","volume":"12","author":"Truong","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/s41592-018-0176-y","article-title":"Species-Level Functional Profiling of Metagenomes and Metatranscriptomes","volume":"15","author":"Franzosa","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D445","DOI":"10.1093\/nar\/gkz862","article-title":"The MetaCyc Database of Metabolic Pathways and Enzymes\u2014A 2019 Update","volume":"48","author":"Caspi","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic Biomarker Discovery and Explanation","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1172\/JCI90562","article-title":"Intestinal Fungi Contribute to Development of Alcoholic Liver Disease","volume":"127","author":"Yang","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1126\/science.1221789","article-title":"Interactions between Commensal Fungi and the C-Type Lectin Receptor Dectin-1 Influence Colitis","volume":"336","author":"Iliev","year":"2012","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41586-019-1742-x","article-title":"Bacteriophage Targeting of Gut Bacterium Attenuates Alcoholic Liver Disease","volume":"575","author":"Duan","year":"2019","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kurtz, Z.D., M\u00fcller, C.L., Miraldi, E.R., Littman, D.R., Blaser, M.J., and Bonneau, R.A. (2015). Sparse and Compositionally Robust Inference of Microbial Ecological Networks. PLoS Comput. Biol., 11.","DOI":"10.1371\/journal.pcbi.1004226"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1214\/009053606000000281","article-title":"High-Dimensional Graphs and Variable Selection with the Lasso","volume":"34","author":"Meinshausen","year":"2006","journal-title":"Ann. Stat."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/2\/143\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:24:03Z","timestamp":1760160243000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/2\/143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,14]]},"references-count":23,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["toxins13020143"],"URL":"https:\/\/doi.org\/10.3390\/toxins13020143","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,14]]}}}