{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:04:04Z","timestamp":1772445844905,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hallym University Research Fund","award":["NRF-2020R1I1A3073530"],"award-info":[{"award-number":["NRF-2020R1I1A3073530"]}]},{"name":"Hallym University Research Fund","award":["NRF-2020R1A6A1A03043026"],"award-info":[{"award-number":["NRF-2020R1A6A1A03043026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Alcoholic liver disease (ALD) is linked to a broad spectrum of diseases, including diabetes, hypertension, atherosclerosis, and even liver carcinoma. The ALD spectrum includes alcoholic fatty liver disease (AFLD), alcoholic hepatitis, and cirrhosis. Most recently, some reports demonstrated that the pathogenesis of ALD is strongly associated with metabolites of human microbiota. AFLD was the onset of disease among ALDs, the initial cause of which is alcohol consumption. Thus, we analyzed the significant metabolites of microbiota against AFLD via the network pharmacology concept. The metabolites from microbiota were retrieved by the gutMGene database; sequentially, AFLD targets were identified by public databases (DisGeNET, OMIM). The final targets were utilized for protein\u2013protein interaction (PPI) networks and signaling pathway analyses. Then, we performed a molecular docking test (MDT) to verify the affinity between metabolite(s) and target(s) utilizing the Autodock 1.5.6 tool. From a holistic viewpoint, we integrated the relationships of microbiota-signaling pathways-targets-metabolites (MSTM) using the R Package. We identified the uppermost six key targets (TLR4, RELA, IL6, PPARG, COX-2, and CYP1A2) against AFLD. The PPI network analysis revealed that TLR4, RELA, IL6, PPARG, and COX-2 had equivalent degrees of value (4); however, CYP1A2 had no associations with the other targets. The bubble chart showed that the PI3K-Akt signaling pathway in nine signaling pathways might be the most significant mechanism with antagonistic functions in the treatment of AFLD. The MDT confirmed that Icaritin is a promising agent to bind stably to RELA (known as NF-\u039ab). In parallel, Bacterium MRG-PMF-1, the PI3K-Akt signaling pathway, RELA, and Icaritin were the most significant components against AFLD in MSTM networks. In conclusion, we showed that the Icaritin\u2013RELA complex on the PI3K-Akt signaling pathway by bacterial MRG-PMF-1 might have promising therapeutic effects against AFLD, providing crucial evidence for further research.<\/jats:p>","DOI":"10.3390\/cimb44070224","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T23:10:22Z","timestamp":1658272222000},"page":"3253-3266","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of Gut Microbiome Metabolites via Network Pharmacology Analysis in Treating Alcoholic Liver Disease"],"prefix":"10.3390","volume":"44","author":[{"given":"Ki-Kwang","family":"Oh","sequence":"first","affiliation":[{"name":"Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9731-4510","authenticated-orcid":false,"given":"Ye-Rin","family":"Choi","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6008-1143","authenticated-orcid":false,"given":"Haripriya","family":"Gupta","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3060-6217","authenticated-orcid":false,"given":"Raja","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satya Priya","family":"Sharma","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Min","family":"Won","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5728-9886","authenticated-orcid":false,"given":"Jin-Ju","family":"Jeong","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su-Been","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Gi","family":"Cha","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goo-Hyun","family":"Kwon","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5792-1500","authenticated-orcid":false,"given":"Dong-Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9206-9245","authenticated-orcid":false,"given":"Ki-Tae","family":"Suk","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/B978-0-323-37591-7.00023-9","article-title":"Natural History and Cofactors of Alcoholic Liver Disease","volume":"1","author":"Liangpunsakul","year":"2018","journal-title":"Zakim Boyer\u2019s Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hyun, J., Han, J., Lee, C., Yoon, M., and Jung, Y. 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