Gut microbiota-derived secondary bile acids, bile acids receptor polymorphisms, and risk of cardiovascular disease in individuals with newly diagnosed type 2 diabetes: a cohort study

法尼甾体X受体 医学 内科学 胆汁酸 胃肠病学 胆酸 危险系数 内分泌学 2型糖尿病 糖尿病 置信区间 生物 生物化学 核受体 基因 转录因子
作者
Qi Lu,Junxiang Chen,Limiao Jiang,Tingting Geng,Shufan Tian,Yunfei Liao,Kun Yang,Yan Zheng,Meian He,Huiru Tang,An Pan,Gang Liu
出处
期刊:The American Journal of Clinical Nutrition [Elsevier BV]
卷期号:119 (2): 324-332 被引量:14
标识
DOI:10.1016/j.ajcnut.2023.08.023
摘要

Secondary bile acids (SBAs), the products of bacterial metabolism, are ligands of the nuclear farnesoid X receptor (FXR) and have been implicated in cardiovascular health. Diet can modulate gut microbiota composition and bile acid metabolism. We aimed to examine the associations of circulating SBAs and their receptor polymorphisms with the risk of incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). A total of 1234 participants with newly diagnosed T2D without CVD or cancer were included from the Dongfeng-Tongji Cohort study in China. Circulating SBAs and their conjugated forms were quantified using liquid chromatography-tandem mass spectrometry. Fifteen single-nucleotide polymorphisms in genes encoding bile acid receptors were genotyped. During a median follow-up of 5.7 y, 259 incident CVD cases were documented. After multivariable adjustment, higher levels of unconjugated SBAs [sum of deoxycholic acid (DCA), lithocholic acid, and ursodeoxycholic acid] and DCA were significantly associated with a higher risk of CVD among people with T2D, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.62 (1.12, 2.35) and 1.46 (1.04, 2.06) comparing the extreme quartile of SBAs and DCA, respectively. Restricted cubic spline regression suggested a linear relationship of unconjugated SBAs and DCA with an elevated risk of CVD, and per standard deviation, an increment in natural log-transformed unconjugated SBAs and DCA was associated with an 18% (95% CI: 4%, 34%) and 16% (95% CI: 2%, 33%) higher risk of CVD, respectively. Moreover, genetic variants in FXR (rs56163822 TT compared with GG, and rs17030295 TT compared with CC) were significantly associated with a 121%–129% higher risk of CVD among individuals with T2D. A higher proportion of unconjugated SBAs, especially DCA, is linearly associated with a higher risk of CVD among people with newly diagnosed T2D. Our findings support the potential role of gut microbiota-derived SBAs in cardiovascular health in individuals with T2D.
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