{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:43:20Z","timestamp":1792899800204,"version":"4.5.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"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>Introduction<\/jats:title><jats:p>Acute liver failure (ALF) is a clinical condition with many causes, fast progression, and a poor prognosis. Previous research has indicated that microbial factors have a role in ALF, but a clear picture has yet to emerge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate the specific involvement of microbial metabolites in ALF development, we pretreated D-GalN\/LPS-induced ALF mice with indole derivatives, an influential class of gut microbial metabolites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Contrary to their typical role as anti-inflammatory agents in the host, indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indolepropionic acid (IPA) gavage sensitize mice to D-GalN\/LPS-induced-ALF with a rapid rise in serum transaminases and histologic lesion. For a clearer picture, we performed comprehensive analysis for the IAA therapy. IAA markedly amplified inflammatory response and cellular damage. The transcriptome analysis indicated the participation of the TNF-\u03b1\/NF-\u03baB signaling pathway. The structure of gut microbiota in ileum and the expression of Toll-like receptor 2 (Tlr2) in the liver were also significantly changed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In conclusion, IAA pretreatment can exacerbate D-GalN\/LPS-induced ALF via probable Tlr2\/NF-\u03baB pathway involvement and ileac dysbiosis characterized by enriched gram-positive genus with potential pathogenesis. Microbial metabolites IAA may aggravate individual susceptibility to D-GalN\/LPS-induced ALF. Further investigation of the underlying mechanism is needed, and intervention with indole derivatives and related commensal species should be undertaken with caution.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2022.1103998","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T13:24:46Z","timestamp":1673011486000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Microbial metabolites indole derivatives sensitize mice to D-GalN\/LPS induced-acute liver failure via the Tlr2\/NF-\u03baB pathway"],"prefix":"10.3389","volume":"13","author":[{"given":"Ziyuan","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaxia","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoqi","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiu","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanjuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut microbiota regulation of tryptophan metabolism in health and disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","article-title":"The gut-liver axis in liver disease: pathophysiological basis for therapy","volume":"72","author":"Albillos","year":"2020","journal-title":"J. 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