Host-dependent alteration of the gut microbiota: the role of luminal microRNAs.

MicroRNAs (miRNAs) are short, non-coding RNAs that play gene expression regulatory roles in eukaryotes. MiRNAs are also released in body fluids, and in the intestine, they are found in the lumen and feces. Here, together with exogenous dietary-derived miRNAs, they constitute the fecal miRNome. Several miRNAs were identified in the feces of healthy adults, including, as shown here, core miRNAs hsa-miR-21-5p and hsa-miR-1246. These miRNAs are important for intestinal homeostasis. Recent evidence suggests that miRNAs may interact with gut bacteria. This represents a new avenue to understand host-bacteria crosstalk in the gut and its role in health and disease. This review provides a comprehensive overview of current knowledge on fecal miRNAs, their representation across individuals, and their effects on the gut microbiota. It also discusses existing evidence on potential mechanisms of uptake and interaction with bacterial genomes, drawing from knowledge of prokaryotic small RNAs (sRNAs) regulation of gene expression. Finally, we review and experimental approaches for profiling miRNA-mRNA interactions in bacterial species, highlighting challenges in target validation. This work emphasizes the need for further research into host miRNA-bacterial interactions to better understand their regulatory roles in the gut ecosystem and support their exploitation for disease prevention and treatment.