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

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

doi:10.1016/j.phrs.2023.106870

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

Pharmacol Res. 2023 Aug:194:106870. doi: 10.1016/j.phrs.2023.106870. Epub 2023 Jul 25.

Authors

Neha Datta¹, Charlotte Johnson², Dina Kao³, Pratik Gurnani⁴, Cameron Alexander⁴, Christos Polytarchou⁵, Tanya M Monaghan⁶

Affiliations

¹ School of Medicine, University of Nottingham, Nottingham, UK.
² NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK; Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.
³ Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
⁴ Division of Molecular Therapeutics & Formulation, School of Pharmacy, University of Nottingham, Nottingham, UK.
⁵ Department of Biosciences, John van Geest Cancer Research Centre, School of Science & Technology, Nottingham Trent University, Nottingham, UK. Electronic address: christos.polytarchou@ntu.ac.uk.
⁶ NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK; Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK. Electronic address: tanya.monaghan@nottingham.ac.uk.

PMID: 37499702
DOI: 10.1016/j.phrs.2023.106870

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.

Keywords: AgomiRs; Alicaforsen (PubChem CID: 16197725); AntagomiRs; Cobomarsen (PubChem CID: 126480232); Delivery mechanisms; Gut-brain axis; Miravirsen (PubChem CID: 56843415); Obefazimod (PubChem CID: 49846599; microRNA (miRNA) therapeutics.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Brain
Brain Diseases*
Brain-Gut Axis
Gastrointestinal Microbiome* / physiology
Humans
Inflammation / genetics
MicroRNAs* / genetics

Substances

MicroRNAs