The Osteoporosis/Microbiota Linkage: The Role of miRNA

Abstract

Hundreds of trillions of bacteria are present in the human body in a mutually beneficial symbiotic relationship with the host. A stable dynamic equilibrium exists in healthy individuals between the microbiota, host organism, and environment. Imbalances of the intestinal microbiota contribute to the determinism of various diseases. Recent research suggests that the microbiota is also involved in the regulation of the bone metabolism, and its alteration may induce osteoporosis. Due to modern molecular biotechnology, various mechanisms regulating the relationship between bone and microbiota are emerging. Understanding the role of microbiota imbalances in the development of osteoporosis is essential for the development of potential osteoporosis prevention and treatment strategies through microbiota targeting. A relevant complementary mechanism could be also constituted by the permanent relationships occurring between microbiota and microRNAs (miRNAs). miRNAs are a set of small non-coding RNAs able to regulate gene expression. In this review, we recapitulate the physiological and pathological meanings of the microbiota on osteoporosis onset by governing miRNA production. An improved comprehension of the relations between microbiota and miRNAs could furnish novel markers for the identification and monitoring of osteoporosis, and this appears to be an encouraging method for antagomir-guided tactics as therapeutic agents.

Keywords: bone metabolism; diet; gene expression; microRNA; microbiota; osteoblast; osteoporosis.

Figure 1

Relationship between gut microbiota and bone mass. An alteration of the gut microbiota can lead to the over-production of inflammatory cytokines, in turn promoting the activation of osteoclasts and bone, leading to bone resorption and inhibiting bone formation, ultimately driving to bone mass reduction and osteoporosis.

Figure 2

Selected microRNAs are known for balancing between bone resorption and formation, having a role in osteoporosis and for targeting several signaling pathways, including Androgen receptor (AR), Wnt, TGF-β, JAK/STAT signaling pathways.

Figure 3

Simplified view of the action of the major intestinal bacteria on osteoporosis through microRNA regulation: (i) Firmicutes are known to modify miR-21 expression, associated with osteoporosis; (ii) Klebsiella pneumoniae drives to increased miR-142 and miR-223, in turn increased in osteoporosis; (iii) E-coli leads to an increase in miR-146a concentration, able to challenge osteoporosis by promoting osteogenesis; (iv) Shigella promotes increased miR-4732-5p concentrations, in turn associated with significant cell growth, also challenging osteoporosis.