The Role of 27 Human Gut Microbiota Genera in Ischemic Heart Disease, Type 2 Diabetes Mellitus and Their Risk Factors: A Mendelian Randomization Study

Abstract

Manipulation of the gut microbiota presents a new opportunity to combat chronic diseases. Randomized controlled trials of probiotics suggest some associations with adiposity, lipids and insulin resistance, but no trials with hard outcomes have been conducted. We used separate-sample Mendelian randomization to obtain estimates of the associations of 27 gut microbiota genera with ischemic heart disease, type 2 diabetes mellitus, adiposity, lipids and insulin resistance, based on summary data from CARDIoGRAAMplusC4D and other consortiums. Among 27 genera, a 1 allele increase in single nucleotide polymorphisms related to higher Bifidobacterium was associated with lower risk of ischemic heart disease (odds ratio = 0.985, 95% confidence interval (CI): 0.971, 1.000, P = 0.04) and 0.011 standard deviation lower body mass index (95% CI: −0.017, −0.005) but 0.026 standard deviation higher low-density lipoprotein cholesterol (95% CI: 0.019, 0.033), which, however, were not robust to exclusion of potential pleiotropy. We also identified Acidaminococcus, Aggregatibacter, Anaerostipes, Blautia, Desulfovibrio, Dorea and Faecalibacterium as nominally associated with type 2 diabetes mellitus or other risk factors. Results from our study indicate that these 8 genera should be given priority in future research relating the gut microbiome to ischemic heart disease and its risk factors.