AUTHOR=Wen Yuhang , Luo Yadan , Qiu Hao , Chen Baoting , Huang Jingrong , Lv Shuya , Wang Yan , Li Jiabi , Tao Lingling , Yang Bailin , Li Ke , He Lvqin , He Manli , Yang Qian , Yu Zehui , Xiao Wudian , Zhao Mingde , Zou Xiaoxia , Lu Ruilin , Gu Congwei TITLE=Gut microbiota affects obesity susceptibility in mice through gut metabolites JOURNAL=Frontiers in Microbiology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1343511 DOI=10.3389/fmicb.2024.1343511 ISSN=1664-302X ABSTRACT=Introduction

It is well-known that different populations and animals, even experimental animals with the same rearing conditions, differ in their susceptibility to obesity. The disparity in gut microbiota could potentially account for the variation in susceptibility to obesity. However, the precise impact of gut microbiota on gut metabolites and its subsequent influence on susceptibility to obesity remains uncertain.

Methods

In this study, we established obesity-prone (OP) and obesity-resistant (OR) mouse models by High Fat Diet (HFD). Fecal contents of cecum were examined using 16S rDNA sequencing and untargeted metabolomics. Correlation analysis and MIMOSA2 analysis were used to explore the association between gut microbiota and intestinal metabolites.

Results

After a HFD, gut microbiota and gut metabolic profiles were significantly different between OP and OR mice. Gut microbiota after a HFD may lead to changes in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), a variety of branched fatty acid esters of hydroxy fatty acids (FAHFAs) and a variety of phospholipids to promote obesity. The bacteria g_Akkermansia (Greengene ID: 175696) may contribute to the difference in obesity susceptibility through the synthesis of glycerophosphoryl diester phosphodiesterase (glpQ) to promote choline production and the synthesis of valyl-tRNA synthetase (VARS) which promotes L-Valine degradation. In addition, gut microbiota may affect obesity and obesity susceptibility through histidine metabolism, linoleic acid metabolism and protein digestion and absorption pathways.