色胺
胰岛素抵抗
代谢综合征
失调
肠易激综合征
苯乙胺
肠道菌群
生物
内分泌学
内科学
药理学
医学
胰岛素
生物化学
糖尿病
作者
Lixiang Zhai,Haitao Xiao,Chengyuan Lin,Hoi Leong Xavier Wong,Yan Y. Lam,Mengxue Gong,Guojun Wu,Ziwan Ning,Chunhua Huang,Yijing Zhang,Chao Yang,Jingyuan Luo,Lu Zhang,Ling Zhao,Chenhong Zhang,Johnson Y. N. Lau,Aiping Lu,Lok Ting Lau,Jia Wang,Liping Zhao,Zhaoxiang Bian
标识
DOI:10.1038/s41467-023-40552-y
摘要
The 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI