AUTHOR=Sanchez-Alcoholado Lidia , Castellano-Castillo Daniel , Jordán-Martínez Laura , Moreno-Indias Isabel , Cardila-Cruz Pilar , Elena Daniel , Muñoz-Garcia Antonio J. , Queipo-Ortuño Maria I. , Jimenez-Navarro Manuel 

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

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.01936

DOI=10.3389/fmicb.2017.01936

ISSN=1664-302X

ABSTRACT=<p>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 <italic>N</italic>-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 <italic>Bacteroidetes</italic> was lower, whereas the phyla <italic>Firmicutes</italic> and <italic>Proteobacteria</italic> 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 <italic>Faecalibacterium prausnitzii</italic> and <italic>Bacteroides fragilis</italic>) and more opportunistic pathogens (such as <italic>Enterobacteriaceae, Streptococcus</italic>, and <italic>Desulfovibrio).</italic> 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 <italic>Enterobacteriaceae</italic> and the decrease in <italic>Faecalibacterium prausnitzii</italic> were significantly associated with the increase in serum TMAO levels, while the decrease in the abundance of <italic>Bacteroides fragilis</italic> 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.</p>