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Gut microbiota composition has been reported as a factor linking host metabolism with the development of cardiovascular diseases (CVD) and intestinal immunity. Such gut microbiota has been shown to aggravate CVD by contributing to the production of trimethylamine  N -oxide (TMAO), which is a pro-atherogenic compound. Treg cells expressing the transcription factor Forkhead box protein P3 (FoxP3) play an essential role in the regulation of immune responses to commensal microbiota and have an atheroprotective role. However, the aim of this study was to analyze the role of gut microbiota on cardio-metabolic parameters and immunity in coronary artery disease (CAD) patients with and without type-2 diabetes mellitus (DM2). The study included 16 coronary CAD-DM2 patients, and 16 age, sex, and BMI matched CAD patients without DM2 (CAD-NDM2). Fecal bacterial DNA was extracted and analyzed by sequencing in a GS Junior 454 platform followed by a bioinformatic analysis (QIIME and PICRUSt). The present study indicated that the diversity and composition of gut microbiota were different between the CAD-DM2 and CAD-NDM2 patients. The abundance of phylum  Bacteroidetes  was lower, whereas the phyla  Firmicutes  and  Proteobacteria  were higher in CAD-DM2 patients than those in the CAD-NDM2 group. CAD-DM2 patients had significantly less beneficial or commensal bacteria (such as  Faecalibacterium prausnitzii  and  Bacteroides fragilis ) and more opportunistic pathogens (such as  Enterobacteriaceae, Streptococcus , and  Desulfovibrio).  Additionally, CAD-DM2 patients had significantly higher levels of plasma zonulin, TMAO, and IL-1B and significantly lower levels of IL-10 and FOXP3 mRNA expression than CAD-NDM2. Moreover, in the CAD-MD2 group, the increase in  Enterobacteriaceae  and the decrease in  Faecalibacterium prausnitzii  were significantly associated with the increase in serum TMAO levels, while the decrease in the abundance of  Bacteroides fragilis  was associated with the reduction in the FOXP3 mRNA expression, implicated in the development and function of Treg cells. These results suggest that the presence of DM2 is related to an impaired regulation of the immune system in CAD patients, mediated in part by the gut microbiota composition and functionality and the production and effects of their gut microbiota derived molecules.

Role of Gut Microbiota on Cardio-Metabolic Parameters and Immunity in Coronary Artery Disease Patients with and without Type-2 Diabetes Mellitus