{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:40:10Z","timestamp":1792518010663,"version":"4.5.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>The composition of the human gut microbiota is linked to health and disease, and knowledge of the impact of therapeutics on the microbiota is essential to decipher their biological roles and to gain new mechanistic insights. Here we report the effect of aldafermin, an analog of the gut hormone FGF19, versus placebo on the gut microbiota in a prospective, phase 2 study in patients with NASH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>A total of 176 patients with biopsy\u2010confirmed nonalcoholic steatohepatitis (NASH) (nonalcoholic fatty liver disease activity score \u2265 4), fibrosis (F1\u2010F3 by NASH Clinical Research Network criteria), and elevated liver fat content (\u2265 8% by magnetic resonance imaging\u2013proton density fat fraction) received 0.3\u00a0mg (n\u00a0=\u00a023), 1\u00a0mg (n\u00a0=\u00a049), 3\u00a0mg (n\u00a0=\u00a049), and 6\u00a0mg (n\u00a0=\u00a028) aldafermin or placebo (n\u00a0=\u00a027) for 12\u00a0weeks. Stool samples were collected on day 1 and week 12 and profiled using 16S ribosomal RNA gene sequencing; 122 patients had paired stool microbiome profiles at both day 1 and week 12. Overall, the state of the gut microbial community was distinctly stable in patients treated with aldafermin, with all major phyla and genera unaltered during therapy. Patients treated with aldafermin showed a significant, dose\u2010dependent enrichment in the rare genus <jats:italic toggle=\"yes\">Veillonella<\/jats:italic>, a commensal microbe known to have lactate\u2010degrading and performance\u2010enhancing properties, which correlated with changes in serum bile acid profile.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>\n                                 <jats:italic toggle=\"yes\">Veillonella<\/jats:italic> may be a bile acid\u2013sensitive bacteria whose enrichment is enabled by aldafermin\u2010mediated suppression of bile acid synthesis and, in particular, decreases in toxic bile acids. This study provides an integrated analysis of gut microbiome, serum bile acid metabolome, imaging, and histological measurements in clinical trials testing aldafermin for NASH. Our results provide a better understanding of the intricacies of microbiome\u2013host interactions (clinicaltrials.gov trial No. NCT02443116).<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31523","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T11:04:16Z","timestamp":1597403056000},"page":"126-143","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":84,"title":["The Commensal Microbe V eillonella as a Marker for Response to an FGF19 Analog in NASH"],"prefix":"10.1097","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-9991","authenticated-orcid":false,"given":"Rohit","family":"Loomba","sequence":"first","affiliation":[{"name":"NAFLD Research Center,University of California, San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ling","sequence":"additional","affiliation":[{"name":"Clinical Research,NGM Biopharmaceuticals Inc.,South San Francisco,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duy M.","family":"Dinh","sequence":"additional","affiliation":[{"name":"Diversigen, Inc.,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex M.","family":"DePaoli","sequence":"additional","affiliation":[{"name":"Clinical Research,NGM Biopharmaceuticals Inc.,South San Francisco,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao D.","family":"Lieu","sequence":"additional","affiliation":[{"name":"Clinical Research,NGM Biopharmaceuticals Inc.,South San Francisco,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Radcliffe Department of Medicine,University of Oxford,London,United Kingdom"},{"name":"Pinnacle Clinical Research,San Antonio,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8682-5748","authenticated-orcid":false,"given":"Arun J.","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Virginia Commonwealth University,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,12,11]]},"reference":[{"key":"hep31523-bib-0001-20250905","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1126\/science.1104816","article-title":"Host\u2010bacterial mutualism in the human intestine","volume":"307","year":"2005","journal-title":"Science"},{"key":"hep31523-bib-0002-20250905","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature18846","article-title":"Diet\u2010microbiota interactions as moderators of human 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