{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:32:17Z","timestamp":1778877137144,"version":"3.51.4"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"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><jats:title>Background\/aim<\/jats:title><jats:p>The purpose of this study was to examine the hepatic bacterial composition and metabolome characteristics of patients with NAFLD using 16S rDNA sequencing and metabolomics. The results of the study revealed substantial differences in hepatic bacterial composition and metabolites between the NAFLD group and the control group. These differences were used to identify potential biomarkers that could be employed to diagnose NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects\/methods<\/jats:title><jats:p>Liver tissues from 13 patients in the NAFLD group and 12 patients in the control group were collected for microbiota examination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The bacterial DNA profiles of the liver were significantly different between NAFLD patients and controls. NAFLD patients exhibited an enrichment of Enterobacterales, Mycobacteriales, Pseudomonadales, Flavobacteriales and Xanthomonadales, Sphingomonadales, Lysobact, which was characterised by a lack of erales. At the genus level, the abundance values of <jats:italic>Escherichia<\/jats:italic>-<jats:italic>Shigella<\/jats:italic>, <jats:italic>Rhodococcus<\/jats:italic>, and <jats:italic>Chryseobacterium<\/jats:italic> in the NAFLD group were significantly elevated, while the abundance values of <jats:italic>Stenotrophomonas<\/jats:italic>, <jats:italic>Lawsonella<\/jats:italic> and <jats:italic>Sphingobium<\/jats:italic> were significantly reduced. A total of 402 distinct metabolites were identified between the two groups, with 78 metabolites that were up-regulated and 14 metabolites that were down-regulated. The enrichment of metabolic pathways indicated that linoleic acid metabolism was the most significant contributor to the metabolic differences, and lipid metabolism was substantially differentiated. The hepatic metabolite levels were substantially correlated with the changes in hepatic microflora, as demonstrated by the correlation analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Differences in pathogenesis and host physiological function of NAFLD may be attributed to the hepatic flora and metabolomic characteristics. In the future, this presents new opportunities for the investigation of prospective diagnostic and therapeutic targets for NAFLD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1528258","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T15:07:32Z","timestamp":1734707252000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterization of the hepatic flora and metabolome in nonalcoholic fatty liver disease"],"prefix":"10.3389","volume":"15","author":[{"given":"Hua","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangfan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yankun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenchen","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianpeng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/hep.28709","article-title":"Bile acids and nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives","volume":"65","author":"Arab","year":"2017","journal-title":"Hepatology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"640","DOI":"10.3390\/biomedicines11020640","article-title":"The effects of probiotics on small intestinal microbiota composition, inflammatory cytokines and intestinal permeability in patients with non-alcoholic fatty liver disease","volume":"11","author":"Ayob","year":"2023","journal-title":"Biomedicines"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"15080","DOI":"10.1038\/nrdp.2015.80","article-title":"Nonalcoholic fatty liver disease","volume":"1","author":"Brunt","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: high-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat. 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Inflamm."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1210\/en.2013-1362","article-title":"11-dehydrocorticosterone causes metabolic syndrome, which is prevented when 11\u03b2-HSD1 is knocked out in livers of male mice","volume":"154","author":"Harno","year":"2013","journal-title":"Endocrinology"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1136\/gutjnl-2017-314307","article-title":"Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD","volume":"67","author":"Jiao","year":"2018","journal-title":"Gut"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"463021","DOI":"10.1016\/j.chroma.2022.463021","article-title":"Liquid chromatography-tandem mass spectrometry based quantification of arginine metabolites including polyamines in different sample matrices","volume":"1671","author":"Langner","year":"2022","journal-title":"J. Chromatogr. 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Food Res."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e0298602","DOI":"10.1371\/journal.pone.0298602","article-title":"High fat diet is associated with gut microbiota dysbiosis and decreased gut microbial derived metabolites related to metabolic health in young G\u00f6ttingen Minipigs","volume":"19","author":"L\u00fctzh\u00f8ft","year":"2024","journal-title":"PLoS One"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.chom.2016.10.016","article-title":"The liver at the nexus of host-microbial interactions","volume":"20","author":"Macpherson","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e3575","DOI":"10.1210\/clinem\/dgaa382","article-title":"Effect of gut microbiota and PNPLA3 rs738409 variant on nonalcoholic fatty liver disease (NAFLD) in obese youth","volume":"105","author":"Monga Kravetz","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"151","DOI":"10.23736\/S0391-1977.16.02583-9","article-title":"Adrenal disorders and non-alcoholic fatty liver disease","volume":"42","author":"Papanastasiou","year":"2017","journal-title":"Minerva Endocrinol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e0215256","DOI":"10.1371\/journal.pone.0215256","article-title":"Faecal volatile biomarkers of Clostridium difficile infection","volume":"14","author":"Patel","year":"2019","journal-title":"PLoS One"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"eaaz2841","DOI":"10.1126\/scitranslmed.aaz2841","article-title":"Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome","volume":"12","author":"Rom","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1007\/s00535-013-0766-5","article-title":"Serum metabolomic profile and potential biomarkers for severity of fibrosis in nonalcoholic fatty liver disease","volume":"48","author":"Tokushige","year":"2013","journal-title":"J. Gastroenterol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.3390\/nano12132162","article-title":"Liposomal form of 2,4-dinitrophenol lipophilic derivatives as a promising therapeutic agent for ATP synthesis inhibition","volume":"12","author":"Vlasova","year":"2022","journal-title":"Nanomaterials"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"5261","DOI":"10.1128\/AEM.00062-07","article-title":"Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy","volume":"73","author":"Wang","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.hbpd.2023.06.006","article-title":"Gut microbiome and nonalcoholic fatty liver disease","volume":"22","author":"Wu","year":"2023","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.jcmgh.2021.12.003","article-title":"Escherichia fergusonii promotes nonobese nonalcoholic fatty liver disease by interfering with host hepatic lipid metabolism through its own msRNA 23487","volume":"13","author":"Xin","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"22385","DOI":"10.1038\/s41598-024-72909-8","article-title":"Altered gut microbial profile accompanied by abnormal short chain fatty acid metabolism exacerbates nonalcoholic fatty liver disease progression","volume":"14","author":"Yang","year":"2024","journal-title":"Sci. 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