MicroRNA and Gut Microbiota: Tiny but Mighty—Novel Insights into Their Cross-talk in Inflammatory Bowel Disease Pathogenesis and Therapeutics

Abstract

MicroRNAs (miRNAs), small non-coding RNAs, have recently been described as crucial contributors to intestinal homeostasis. They can interact with the gut microbiota in a reciprocal manner and deeply impact the host health status, leading to several disorders when unbalanced. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract that co-occurs with alterations of the gut microbiota, and whose aetiology remains largely unclear. On one hand, host miRNA could be playing a relevant role in IBD pathophysiology by shaping the gut microbiota. The gut microbiome, on the other hand, may regulate the expression of host miRNAs resulting in intestinal epithelial dysfunction, altered autophagy, and immune hyperactivation. Interestingly, it has been hypothesized that their reciprocal impact may be used for therapeutic goals. This review describes the latest research and suggests mechanisms through which miRNA and intestinal microbiota, as joint actors, may participate specifically in IBD pathophysiology. Furthermore, we discuss the diagnostic power and therapeutic potential resulting from their bidirectional communication after faecal transplantation, probiotics intake, anti-miRNAs or miRNA mimics administration. The current literature is summarized in the present work in a comprehensive manner hoping to provide a better understanding of the miRNA-microbiota crosstalk and to facilitate their application in IBD.

MicroRNAs in Inflammatory Bowel Disease and Its Complications

“…Current therapeutic interventions for IBD include aminosalicylates, thiopurines, corticosteroids, and biologics [ 94 ]. Therapeutic use of miRNAs is being considered within research as a novel treatment agent due to the ability of miRNAs to simultaneously modulate multiple gene targets [ 95 ].…”

“…miRNA antagomirs may also augment existing clinical therapies with let-7a inhibition increasing Fas and Fas ligand in bone-marrow-derived mesenchymal stem cells to induce T cell migration and apoptosis to ultimately maximize mesenchymal stem cell cytotherapy benefits [ 99 ]. miRNAs may be a candidate for future therapeutic usage, and currently, Miravirsen is an antimir used for treating the hepatitis C virus (HCV) through targeting miR-122-HCV inhibition and is currently in phase II clinical drug trials [ 94 ]. However, antagomir therapy faces hurdles including a lack of specificity for target cells, potential hepatotoxicity, and potential side effects due to vast miRNA gene modulation [ 94 , 97 ].…”

“…miRNAs may be a candidate for future therapeutic usage, and currently, Miravirsen is an antimir used for treating the hepatitis C virus (HCV) through targeting miR-122-HCV inhibition and is currently in phase II clinical drug trials [ 94 ]. However, antagomir therapy faces hurdles including a lack of specificity for target cells, potential hepatotoxicity, and potential side effects due to vast miRNA gene modulation [ 94 , 97 ]. While liposomal packaging and serum exosomal therapy are suggested as potential solutions, experiments must be replicated in larger cohorts and the variety of animal models increased to ascertain true clinical viability.…”

“…Agomirs or miRNA mimics are useful for rescuing the downregulation of miRNA in certain pathological states. However, agomir therapy faces additional hurdles such as a larger dosage requirement and the challenge of incorporating the miRNA into the fully functional RISC complex [ 94 ]. miRNA mimics are also being used as burgeoning treatments in oncology with MRX34, a liposomal encapsulated miR-34a mimic, currently in phase I clinical drug trials.…”

Global trends in research on miRNA–microbiome interaction from 2011 to 2021: A bibliometric analysis

“…In 2016, Liu et al (2016) demonstrated that host fecal miRNAs may be able to alter bacterial composition by targeting bacterial genes selectively; this finding was a crucial milestone in understanding the mechanism of the interaction between the microbiome and miRNA. Dysregulation of the symbiosis between the miRNA and the microbiota is linked with a range of diseaseas, which include inflammatory bowel disease (IBD), colon cancer, and neurological disorders ( Ragusa et al, 2020 ; Cao et al, 2021 ; Casado-Bedmar and Viennois, 2021 ). Recently, miRNA–microbiome interplay has become a research hotspot and the focus of many reviews ( Jiayi et al, 2019 ; Deepansh et al, 2021 ), but comprehensive and visual reviews in this field are limited.…”