Gut Microbiota (GM), a microbial community gathering more than 100 trillion microorganisms in gastrointestinal tract, plays specific functions as nutrient metabolism, gut mucosa integrity, immunomodulation and protection against pathogens; GM also controls adipose tissue expansion and food intake. One of the major difficulties in GM study is the ability to culture its microorganisms; since GM encodes over 3 million genes producing thousands of metabolites, recent technologies have allowed to phylogenetically identify and quantify GM components by analyzing nucleic acids directly extracted from stools.
microRNAs (miRNAs) are short noncoding RNA sequences regulating biological, metabolic and cellular processes; miRNAs may also have a role in molecular mechanisms linked to pathways of some diseases, including diabetes, obesity and cardiovascular disease. Discovery of miRNAs easily measurable in plasma and other body fluids, led to the hypothesis of their potential role as disease indicators.
There is evidence of correlation between alterations of GM composition and several gastrointestinal disorders, as Irritable Bowel Syndrome, Inflammatory Bowel Disease (IBD), Celiac Disease and Colorectal Cancer(CRC), and also metabolic disorders and brain-related disorders, although GM role in their pathogenesis is poorly understood yet.
Intestinal miRNAs develop from two main sources: the host and the food; intestinal epithelial cells are the main contributors of host-derived miRNAs, instead miRNAs from food can be absorbed by host and can affect its gene expression; moreover, dietary components are capable to modify miRNA expression. Several miRNAs can have specific effects on gut bacterial growth and influence survival and composition of gut bacteria; in addition miRNAs can enter bacteria and alter bacterial gene. Tthe abundance of miRNA can be inversely correlated with the abundance of microbes and this suggests that microbes might take up miRNAs and these miRNAs might in turn affect microbes.
On the other hand, GM regulates host miRNAs expression in the gut, suggesting that GM can control host innate immune responses by regulating of miRNA expression. It has been proved that fecal microbiota transplantation has high capacity for treating different diseases and GM can be shaped by administration of fecal miRNAs; this is an important potential of application since diseases related to changes in GM might be treated using synthetic specific miRNAs.
In nearly all studies, detection of miRNAs was performed on stools or gut tissue samples; these procedures were preferred to detection of circulating miRNAs and much stronger miRNA expression changes were observed in feces. Fecal miRNAs, whose profile can dependent on functionally relevant GM alterations, could be used as a new tool to assess microbiota healthiness.
Dysregulation of fecal miRNAs was found over all in CRC and in IBD whereas there is poor evidence in other gastrointestinal disorders and GM dysbiosis related diseases; in these cases, links between miRNAs dysregulation and GM are still unclear and uncertain. It must be expected that miRNAs play a role in mediating host–microbiota metabolic interactions.
Additional studies are needed to understand miRNA-microbiota interactions and delineate their precise mechanisms, in addition to establishing which kinds of microbiota can modulate miRNA expression by combining high-throughput technologies.
Audience Take Away:
- This review focus on: 1) potential future role of microRNAs in the Gut Microbioma study; 2) possible application of microRNA detection as disease indicators; 3) potential of application in the treatment of diseases related to Gut Microbiota dysbiosis using synthetic specific miRNAs (gene-targeting therapy?).
- This work could further stimulate the Researchers; if presented data will be confirmed in more extensive studies including a larger number of patients, they could improve early diagnosis, follow-up and treatment of Gut Microbiota dysbiosis and its relate diseases (over all Colorectal cancer). In this way, I think the effort would be significantly remarkable.
- Next step will be to evaluate whether microRNAs detection can be applied in future daily clinical practice and routine examinations.
- Main limits/criticisms: costs and availability of quantifying techniques; high detection cost is the main limitations on the use of these nucleotides in daily clinical practice; new low-cost and wide availability assays to detect microRNA with high sensitivity and specificity are need.
Angelo Michele Carella after graduating in Medicine, have obtained specialization in Internal Medicine, university Master in Healthcare Management and postgraduate courses on Diabetes and Obesity. Medical Doctor at the Internal Medicine Department of "T. Masselli - Mascia" Hospital in San Severo (Italy). Past teacher at Health Professions degree course of Foggia Medical University. Editorial Board member/Reviewer of several scientific journals; Author of about 50 scientific publications; Member of D&CVD EASD Study Group; Investigator in clinical studies (DAVID, ESPORT, ATA-AF, DIAMOND) published in international journals; Speaker at numerous scientific congresses and meetings. Rregistered in ORCID, Google Scholar and Research Gate.