MicroRNA-based therapeutics for inflammatory disorders of the microbiota-gut-brain axis

Datta, Neha; Johnson, Charlotte; Kao, Dina; Gurnani, Pratik; Alexander, Cameron; Polytarchou, Christos; Monaghan, Tanya M.

Abstract

An emerging but less explored shared pathophysiology across microbiota-gut-brain axis disorders is aberrant miRNA expression, which may represent novel therapeutic targets. miRNAs are small, endogenous non-coding RNAs that are important transcriptional repressors of gene expression. Most importantly, they regulate the integrity of the intestinal epithelial and blood-brain barriers and serve as an important communication channel between the gut microbiome and the host. A well-defined understanding of the mode of action, therapeutic strategies and delivery mechanisms of miRNAs is pivotal in translating the clinical applications of miRNA-based therapeutics. Accumulating evidence links disorders of the microbiota-gut-brain axis with a compromised gut-blood-brain-barrier, causing gut contents such as immune cells and microbiota to enter the bloodstream leading to low-grade systemic inflammation. This has the potential to affect all organs, including the brain, causing central inflammation and the development of neurodegenerative and neuropsychiatric diseases. In this review, we have examined in detail miRNA biogenesis, strategies for therapeutic application, delivery mechanisms, as well as their pathophysiology and clinical applications in inflammatory gut-brain disorders. The research data in this review was drawn from the following databases: PubMed, Google Scholar, and Clinicaltrials.gov. With increasing evidence of the pathophysiological importance for miRNAs in microbiota-gut-brain axis disorders, therapeutic targeting of cross-regulated miRNAs in these disorders displays potentially transformative and translational potential. Further preclinical research and human clinical trials are required to further advance this area of research.

Citation

Datta, N., Johnson, C., Kao, D., Gurnani, P., Alexander, C., Polytarchou, C., & Monaghan, T. M. (2023). MicroRNA-based therapeutics for inflammatory disorders of the microbiota-gut-brain axis. Pharmacological Research, 194, Article 106870. https://doi.org/10.1016/j.phrs.2023.106870

• Journal Article Type: Review
• Acceptance Date: Jul 24, 2023
• Online Publication Date: Jul 26, 2023
• Publication Date: Aug 1, 2023
• Deposit Date: Jul 26, 2023
• Publicly Available Date: Jul 26, 2023
• Journal: Pharmacological Research
• Print ISSN: 1043-6618
• Electronic ISSN: 1096-1186
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 194
• Article Number: 106870
• DOI: https://doi.org/10.1016/j.phrs.2023.106870
• Keywords: MicroRNA (miRNA) therapeutics; gut-brain axis; delivery mechanisms; antagomiRs; agomiRs
• Public URL: https://nottingham-repository.worktribe.com/output/23478767
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1043661823002268?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: MicroRNA-based therapeutics for inflammatory disorders of the microbiota-gut-brain axis; Journal Title: Pharmacological Research; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.phrs.2023.106870; Content Type: article; Copyright: © 2023 The Authors. Published by Elsevier Ltd.