The Roles of 27 Genera of Human Gut Microbiota 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 to our knowledge no trials with "hard" outcomes have been conducted. We used separate-sample Mendelian randomization to obtain estimates of the associations of 27 genera of gut microbiota with ischemic heart disease, type 2 diabetes mellitus, adiposity, lipid levels, and insulin resistance, based on summary data from CARDIoGRAAMplusC4D and other consortia. Among the 27 genera, a 1-allele increase in single nucleotide polymorphisms related to greater abundance of 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), a 0.011-standard-deviation lower body mass index (95% CI: -0.017, -0.005), and a 0.026-standard-deviation higher low-density lipoprotein cholesterol level (95% CI: 0.019, 0.033), but the findings were not robust to exclusion of potential pleiotropy. We also identified Acidaminococcus, Aggregatibacter, Anaerostipes, Blautia, Desulfovibrio, Dorea, and Faecalibacterium as being nominally associated with type 2 diabetes mellitus or other risk factors. Results from our study indicate that these 8 genera of gut microbiota should be given priority in future research relating the gut microbiome to ischemic heart disease and its risk factors.

The Gut Microbial Diversity of Newly Diagnosed Diabetics but Not of Prediabetics Is Significantly Different from That of Healthy Nondiabetics

“…Observations of high abundance of Lactobacillus (3) and decreased abundance of Akkermansia in NewDMs corroborate previous findings (5). In KnownDMs, we found increased abundance of Megasphaera, Escherichia, and Acidaminococcus and decreased abundance of Sutterella, which is similar to earlier findings (6,(49)(50)(51). de la Cuesta-Zuluaga et al reported that metformin treatment in diabetics is associated with increased abundance of Megasphaera in the Colombian population (39).…”

mbImpute: an accurate and robust imputation method for microbiome data

“…supported by both 16S rRNA and WGS data after imputation. Notably, in the magenta squares, Acidaminococcus has correlations with Dialister and Blautia only after imputation, and this result is consistent with the literature: Acidaminococcus and Dialister are both reported to have low abundances in healthy human stool samples[89]; Acidaminococcus and Blautia are both associated with risks of T2D and obesity, lipid profiles, and homeostatic model assessment of insulin resistance[90]. The green squares contain three bile-tolerant genera: Alistipes, Bilophila,…”

Association Of Gut Microbiota During Early Pregnancy With Risk Of Incident Gestational Diabetes Mellitus: A Nested Case-Control Study

“…Besides the main results from nal conditional Logistic regression analyses, we also found signs of gut microbial dysbiosis indicated by signi cantly differentiated relative abundances in other taxa. For instance, SCFA producing Anaerostipes was under-represented in GDM group and has been previously found nominally associated with type 2 diabetes mellitus [26], which was elevated along with alleviation of in ammation in animal models [27,28]. On the other hand, we found several taxa including Ruminococcaceae spp., Veillonellaceae and opportunistic pathogens Enterobacteriaceae of Proteobacteria were signi cantly over-represented in GDM cases.…”