{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:43:19Z","timestamp":1792449799897,"version":"4.5.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"35","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"MOST | National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFA0900404"],"award-info":[{"award-number":["2018YFA0900404"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22134003"],"award-info":[{"award-number":["22134003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,8,27]]},"abstract":"<jats:p>\n                    Type 2 diabetes (T2D) is potentially linked to disordered tryptophan metabolism that attributes to the intricate interplay among diet, gut microbiota, and host physiology. However, underlying mechanisms are substantially unknown. Comparing the gut microbiome and metabolome differences in mice fed a normal diet (ND) and high-fat diet (HFD), we uncover that the gut microbiota\u2013dependent tryptophan metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) is present at lower concentrations in mice with versus without insulin resistance. We further demonstrate that the microbial transformation of tryptophan into 5-HIAA is mediated by\n                    <jats:italic>Burkholderia<\/jats:italic>\n                    spp. Additionally, we show that the administration of 5-HIAA improves glucose intolerance and obesity in HFD-fed mice, while preserving hepatic insulin sensitivity. Mechanistically, 5-HIAA promotes hepatic insulin signaling by directly activating AhR, which stimulates TSC2 transcription and thus inhibits mTORC1 signaling. Moreover, T2D patients exhibit decreased fecal levels of 5-HIAA. Our findings identify a noncanonical pathway of microbially producing 5-HIAA from tryptophan and indicate that 5-HIAA might alleviate the pathogenesis of T2D.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2400385121","type":"journal-article","created":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T21:31:12Z","timestamp":1724275872000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":83,"title":["The microbiota-dependent tryptophan metabolite alleviates high-fat diet\u2013induced insulin resistance through the hepatic AhR\/TSC2\/mTORC1 axis"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5324-2607","authenticated-orcid":false,"given":"Wei","family":"Du","sequence":"first","affiliation":[{"name":"Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, 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