文献类型：期刊文献

英文题名：The microbiota- dependent tryptophan metabolite alleviates high- fat diet-induced insulin resistance through the hepatic AhR/TSC2/mTORC1 axis

作者：Du, Wei[1];Jiang, Shanshan[2];Yin, Shengxiang[2];Wang, Rongjiang[2];Zhang, Chunling[2];Yin, Bin - Cheng[1];Li, Jialin[3];Li, Li[3];Qi, Nan[2,4];Zhou, Ying[1];Ye, Bang-Ce[1,2,4]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Lab Biosyst & Microanal, Shanghai 200237, Peoples R China;[2]Zhejiang Univ Technol, Inst Engn Biol & Hlth, Coll Pharmaceut Sci, Collaborat Innovat Ctr Yangtze River Delta Reg Gre, Hangzhou 310014, Zhejiang, Peoples R China;[3]Ningbo First Hosp, Dept Endocrinol & Metab, Ningbo 315010, Zhejiang, Peoples R China;[4]Guangzhou Natl Lab, Guangzhou Int Bio isl, Guangzhou 510005, Guangdong, Peoples R China

年份：2024

卷号：121

期号：35

外文期刊名：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001415697900001)】；

基金：ACKNOWLEDGMENTS . This work was supported by grants from the National Natural Science Foundation of China (22134003) and National Key Research and Development Program of China (2018YFA0900404) . We thank Dr. Yanjing Li (East China University of Science and Technology) for the insightful discussion.

语种：英文

外文关键词：gut microbiota; tryptophan metabolism; insulin signaling; type 2 diabetes

摘要：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-dependent 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 Burkholderia spp. Additionally, we show that the administration of 5- HIAA improves glucose intolerance and obesity in HFD- fed mice, 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.