Wang Yan, Lv Bohan, Liu Nannan, Tao Siyu, Dou Jinfang, Li Jun, Deng Ruxue, Yang Xiuyan, Jiang Guangjian
Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, China.
Department of Endocrinology, Beijing He ping li Hospital, Beijing, China.
Heliyon. 2024 Aug 12;10(16):e35421. doi: 10.1016/j.heliyon.2024.e35421. eCollection 2024 Aug 30.
The main objective of this study was to analyze the changes of intestinal microflora and how bile acid metabolic pathways affect lipid metabolism in T2DM through the gut-liver axis.
Firstly, 16S rRNA sequencing, metabolomics and transcriptomic sequencing were performed on plasma and feces of clinical subjects to determine the changes of intestinal flora and its metabolites. Finally, T2DM mice model was verified .
T2DM patients have significant intestinal flora metabolism disorders. The differential fecal metabolites were mainly enriched in primary bile acid biosynthesis and cholesterol metabolism pathways in T2DM patients. After verification, the changes in gut microbiota and metabolites in T2DM patients (including up-regulated bacteria associated with BA metabolism, such as and , and down-regulated bacteria capable of producing SCFAs such as and ); and the changes in the flora and metabolites that result in impairment of intestinal barrier function and changes of protein expression in the blood, intestine and liver of T2DM patients (including FGFR4↑, TRPM5↑ and CYP27A1↓, which are related to BA and lipid metabolism homeostasis, and TLR6↑, MYD88↑ and NF-κB↑, which are related to inflammatory response). These aspects together contribute to the development of further disorders of glucolipid metabolism and systemic inflammation in T2DM patients.
Changes in intestinal flora and its metabolites may affect lipid metabolism and systemic inflammatory response in T2DM patients through the gut-liver axis mediated by bile acids.
本研究的主要目的是通过肠-肝轴分析2型糖尿病（T2DM）患者肠道微生物群的变化以及胆汁酸代谢途径如何影响脂质代谢。
首先，对临床受试者的血浆和粪便进行16S rRNA测序、代谢组学和转录组测序，以确定肠道菌群及其代谢产物的变化。最后，验证T2DM小鼠模型。
T2DM患者存在明显的肠道菌群代谢紊乱。T2DM患者粪便中差异代谢产物主要富集在初级胆汁酸生物合成和胆固醇代谢途径中。验证后发现，T2DM患者肠道微生物群和代谢产物的变化（包括与胆汁酸代谢相关的上调细菌，如 和 ，以及能够产生短链脂肪酸的下调细菌，如 和 ）；以及导致T2DM患者肠道屏障功能受损以及血液、肠道和肝脏中蛋白质表达变化的菌群和代谢产物变化（包括与胆汁酸和脂质代谢稳态相关的FGFR4↑、TRPM5↑和CYP27A1↓，以及与炎症反应相关的TLR6↑、MYD88↑和NF-κB↑）。这些方面共同促成了T2DM患者糖脂代谢进一步紊乱和全身炎症的发展。
肠道菌群及其代谢产物的变化可能通过胆汁酸介导的肠-肝轴影响T2DM患者的脂质代谢和全身炎症反应。
