Novel Interactions Between Circulating microRNAs and Gut Microbiota Composition in Human Obesity.

Abstract Background: Unbalances in microRNAs (miRNA) and gut microbiota patterns have been proposed as putative factors concerning onset and development of obesity and other metabolic diseases. However, the determinants that mediate the interactions between miRNAs and the gut microbiome impacting on obesity are scarcely understood. Thus, the aim of this article was to investigate possible interactions between circulating miRNAs and gut microbiota composition in obesity. Method: The analyzed sample comprised 78 subjects with obesity [cases, body mass index (BMI): 30 – 40 kg/m2] and 25 eutrophic individuals (controls, BMI £ 25 kg/m2). The expression of 96 miRNAs was investigated in plasma of all individuals using miRCURY LNA miRNA Custom PCR Panels (Exiqon). Bacterial DNA sequencing was performed following the Illumina 16S protocol. The FDR (Benjamini-Hochberg test, q-value) correction was used for multiple comparison analyses.Results: A total of 26 circulating miRNAs and 12 bacterial species were found differentially expressed between cases and controls. Interestingly, an interaction among three miRNAs (miR-130b-3p, miR-185-5p, and miR-21-5p) with Bacteroides eggerthi, and BMI levels was evidenced (r2= 0.148, P= 0.004). Those miRNAs that correlated with obesity-associated gut bacteria abundance are known to regulate target genes that participate in metabolism-related pathways, such as fatty acid degradation, carbohydrate digestion and absorption, insulin signaling, and glycerolipid metabolism. Conclusion: This study characterized an interaction between the abundance of 4 bacterial species and 14 circulating miRNAs in relation to body adiposity. Moreover, the current study also suggests that miRNAs may serve as a communication mechanism between the gut microbiome and human hosts. Clinical trial registration: clinicaltrials.gov (reg. no. NCT02737267).