Effects of therapeutic probiotics on modulation of microRNAs

Abstract

Probiotics are beneficial bacteria that exist within the human gut, and which are also present in different food products and supplements. They have been investigated for some decades, due to their potential beneficial impact on human health. Probiotics compete with pathogenic microorganisms for adhesion sites within the gut, to antagonize them or to regulate the host immune response resulting in preventive and therapeutic effects. Therefore, dysbiosis, defined as an impairment in the gut microbiota, could play a role in various pathological conditions, such as lactose intolerance, gastrointestinal and urogenital infections, various cancers, cystic fibrosis, allergies, inflammatory bowel disease, and can also be caused by antibiotic side effects. MicroRNAs (miRNAs) are short non-coding RNAs that can regulate gene expression in a post-transcriptional manner. miRNAs are biochemical biomarkers that play an important role in almost all cellular signaling pathways in many healthy and disease states. For the first time, the present review summarizes current evidence suggesting that the beneficial properties of probiotics could be explained based on the pivotal role of miRNAs. Video Abstract.

Keywords: Biomarkers; Cancer; Inflammatory bowel disease; MicroRNAs; Probiotics; Supplements.

Fig 1

Major mechanisms of action of probiotics. Probiotics exert its therapeutic effects via different mechanisms including enhancement of epithelial barrier, inhibition of pathogen adhesion, and modulation of immune system. This figure adapted from  Bermudez-Brito  et al (Ann Nutr Metab 2012;61:160–174)

Fig 2

Biogenesis of miRNA. Starts in the nucleus when miRNA genes are transcribed by RNA polymerase II as large polyadenylated RNA molecules named primary miRNAs (pri-miRNAs). Pri-miRNAs are processed in the nucleus by RNase III Drosha and microprocessor complex subunit DGCR8. As a result, pri-miRNAs are cleaved into smaller double-stranded RNA (dsRNA) molecules known as pre-miRNAs and then are exported to the cytoplasm by exportin 5 (XPO5). Pre-miRNAs in the cytoplasm are cleaved and despoiled of their loops by the RNase III enzyme Dicer in association with TRBP into mature miRNAs consisting of a ∼22-nucleotide duplex. The last processing step is carried out by a ribonucleoprotein complex known as RNA-induced silencing complex (RISC), which can unwind both strands. Although either strand of the miRNA duplex could potentially act as a mature miRNA, usually only one of the strands is incorporated into the RISC complex to induce mRNA silencing. RISC-loading complex (RLC), consisted of Dicermm, Argonaute 2 (Ago2), and TRBP. Once loaded, the RISC complex finds a complementary strand, activates RNase and cleaves the RNA

Fig 3

A schema of anti- apoptotic effects of probiotics. Various microRNAs i.e., miR-21, miR-200b and miR-21 can indirectly affect on apoptosis pathways