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Article: Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome

TitleGut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome
Authors
Issue Date2023
Citation
Nature Communications, 2023, v. 14, n. 1, article no. 4986 How to Cite?
AbstractThe incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota is causatively linked with the development of both metabolic dysfunctions and gastrointestinal disorders, thus gut dysbiosis in IBS may contribute to the development of metabolic syndrome. Here, we show that human gut bacterium Ruminococcus gnavus-derived tryptamine and phenethylamine play a pathogenic role in gut dysbiosis-induced insulin resistance in type 2 diabetes (T2D) and IBS. We show levels of R. gnavus, tryptamine, and phenethylamine are positively associated with insulin resistance in T2D patients and IBS patients. Monoassociation of R. gnavus impairs insulin sensitivity and glucose control in germ-free mice. Mechanistically, treatment of R. gnavus-derived metabolites tryptamine and phenethylamine directly impair insulin signaling in major metabolic tissues of healthy mice and monkeys and this effect is mediated by the trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. Our findings suggest a causal role for tryptamine/phenethylamine-producers in the development of insulin resistance, provide molecular mechanisms for the increased prevalence of metabolic syndrome in IBS, and highlight the TAAR1 signaling axis as a potential therapeutic target for the management of metabolic syndrome induced by gut dysbiosis.
Persistent Identifierhttp://hdl.handle.net/10722/342678
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhai, Lixiang-
dc.contributor.authorXiao, Haitao-
dc.contributor.authorLin, Chengyuan-
dc.contributor.authorWong, Hoi Leong Xavier-
dc.contributor.authorLam, Yan Y.-
dc.contributor.authorGong, Mengxue-
dc.contributor.authorWu, Guojun-
dc.contributor.authorNing, Ziwan-
dc.contributor.authorHuang, Chunhua-
dc.contributor.authorZhang, Yijing-
dc.contributor.authorYang, Chao-
dc.contributor.authorLuo, Jingyuan-
dc.contributor.authorZhang, Lu-
dc.contributor.authorZhao, Ling-
dc.contributor.authorZhang, Chenhong-
dc.contributor.authorLau, Johnson Yiu Nam-
dc.contributor.authorLu, Aiping-
dc.contributor.authorLau, Lok Ting-
dc.contributor.authorJia, Wei-
dc.contributor.authorZhao, Liping-
dc.contributor.authorBian, Zhao Xiang-
dc.date.accessioned2024-04-17T07:05:28Z-
dc.date.available2024-04-17T07:05:28Z-
dc.date.issued2023-
dc.identifier.citationNature Communications, 2023, v. 14, n. 1, article no. 4986-
dc.identifier.urihttp://hdl.handle.net/10722/342678-
dc.description.abstractThe incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota is causatively linked with the development of both metabolic dysfunctions and gastrointestinal disorders, thus gut dysbiosis in IBS may contribute to the development of metabolic syndrome. Here, we show that human gut bacterium Ruminococcus gnavus-derived tryptamine and phenethylamine play a pathogenic role in gut dysbiosis-induced insulin resistance in type 2 diabetes (T2D) and IBS. We show levels of R. gnavus, tryptamine, and phenethylamine are positively associated with insulin resistance in T2D patients and IBS patients. Monoassociation of R. gnavus impairs insulin sensitivity and glucose control in germ-free mice. Mechanistically, treatment of R. gnavus-derived metabolites tryptamine and phenethylamine directly impair insulin signaling in major metabolic tissues of healthy mice and monkeys and this effect is mediated by the trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. Our findings suggest a causal role for tryptamine/phenethylamine-producers in the development of insulin resistance, provide molecular mechanisms for the increased prevalence of metabolic syndrome in IBS, and highlight the TAAR1 signaling axis as a potential therapeutic target for the management of metabolic syndrome induced by gut dysbiosis.-
dc.languageeng-
dc.relation.ispartofNature Communications-
dc.titleGut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/s41467-023-40552-y-
dc.identifier.pmid37591886-
dc.identifier.scopuseid_2-s2.0-85168274894-
dc.identifier.volume14-
dc.identifier.issue1-
dc.identifier.spagearticle no. 4986-
dc.identifier.epagearticle no. 4986-
dc.identifier.eissn2041-1723-
dc.identifier.isiWOS:001067877800014-

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