Association of gut microbiota composition and their metabolites with subclinical atheromatosis: A systematic review

Study objective: The present systematic review investigates the hypothesis that specific components of the intestinal microbiome and/or their metabolites are associated with early stages of subclinical arterial damage (SAD).Design: Based on the MOOSE criteria, we conducted a systematic review of the literature (Scopus, Medline) investigating the potential association between gut microbiota and the most widely applied arterial biomarkers of SAD.Participants: All studies included individuals without established cardiovascular disease, either with or without SAD.Intervention: No interventions were made.Main outcome measures: Association between exposure (components/metabolites of microbiota) and outcome (presence of SAD).Results: Fourteen articles met the predefined criteria. Due to the large heterogeneity, their meta-analysis was not possible. Our review revealed (a) two studies on endothelial dysfunction, out of which one found an inverse relation between plasma trimethylamine N-oxide levels and FMD and the other did not substantiate a statistically significant correlation with RHI. (b) Twelve studies on atheromatosis, assessed as intimal-medial thickness (IMT), coronary artery calcium (CAC) and arterial plaque, of which, seven studies showed statistically significant associations (negative or positive depending on the microorganism or microbiota metabolite) with IMT, one study revealed significant associations with coronary artery calcium, while one showed absence of correlation and four studies reported statistically significant correlations with arterial plaque. (c) Three studies on arterial stiffness (pulse wave velocity - PWV) with two of them concluding in statistically significant association while the third study did not. Some articles investigated multiple of the correlations described and therefore, belonged to more than one section. Conclusion: Evidence of both positive and inverse associations of gut microbiota composition and their metabolites with different types of SVD has been found. However the small number and heterogeneity of available studies cannot allow to confirm or disprove the hypothesis.