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
Laboratory Animal Centre, Southwest Medical University, Luzhou, China.
Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China.
Front Microbiol. 2024 Feb 21;15:1343511. doi: 10.3389/fmicb.2024.1343511. eCollection 2024.
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.
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.
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 (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.
众所周知，不同人群和动物，即使是饲养条件相同的实验动物，对肥胖的易感性也存在差异。肠道微生物群的差异可能是导致肥胖易感性变化的原因。然而，肠道微生物群对肠道代谢物的精确影响及其对肥胖易感性的后续影响仍不明确。
在本研究中，我们通过高脂饮食（HFD）建立了肥胖倾向（OP）和肥胖抵抗（OR）小鼠模型。使用16S rDNA测序和非靶向代谢组学检测盲肠的粪便内容物。采用相关性分析和MIMOSA2分析来探索肠道微生物群与肠道代谢物之间的关联。
高脂饮食后，OP小鼠和OR小鼠的肠道微生物群和肠道代谢谱存在显著差异。高脂饮食后的肠道微生物群可能导致二十碳五烯酸（EPA）、二十二碳六烯酸（DHA）、多种羟基脂肪酸支链脂肪酸酯（FAHFAs）和多种磷脂的变化，从而促进肥胖。细菌（Greengene ID：175696）可能通过合成甘油磷酸二酯磷酸二酯酶（glpQ）促进胆碱生成以及合成促进L-缬氨酸降解的缬氨酰-tRNA合成酶（VARS），导致肥胖易感性的差异。此外，肠道微生物群可能通过组氨酸代谢、亚油酸代谢以及蛋白质消化和吸收途径影响肥胖及肥胖易感性。
