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Connecting inflammatory bowel and neurodegenerative diseases: microRNAs as a shared therapeutic intervention
  1. Tanya M Monaghan1,2,
  2. Aslihan Ugun-Klusek3,
  3. Mattea Finelli4,
  4. Pratik Gurnani5,
  5. Lisa Chakrabarti6,7,
  6. Dina Kao8,
  7. Cameron Alexander5,
  8. Christos Polytarchou3,9
  1. 1 NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK
  2. 2 Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
  3. 3 Department of Biosciences, Centre for Health, Ageing and Understanding Disease (CHAUD), School of Science and Technology, Nottingham Trent University, Nottingham, UK
  4. 4 School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, UK
  5. 5 Division of Molecular Therapeutics & Formulation, School of Pharmacy, University of Nottingham, Nottingham, UK
  6. 6 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
  7. 7 MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, Nottingham, UK
  8. 8 Division of Gastroenterology, Department of Medicine, University of Alberta Hospital, Edmonton, Alberta, Canada
  9. 9 John van Geest Cancer Research Centre, School of Science & Technology, Nottingham Trent University, Nottingham, UK
  1. Correspondence to Dr Tanya M Monaghan, University of Nottingham, Nottingham, UK; tanya.monaghan{at}nottingham.ac.uk

https://doi.org/10.1136/gutjnl-2022-327301

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    We read with interest the recent article by Zhang et al that reported a higher risk of developing dementia in patients with inflammatory bowel disease (IBD), with the largest increase in Alzheimer’s disease (AD).1 These findings align with a growing body of evidence which links gut inflammation or leaky gut with neurodegeneration. Lee et al discussed the known shared pathophysiological links between IBD and Parkinson’s disease (PD), underscoring the importance of genetic overlap, microbiota gut-brain axis, autoimmunity, mitochondrial function and autophagy.2 We would like to highlight another less-explored biological connection: microRNAs (miRNAs).

    miRNAs are small non-coding RNAs, which regulate gene expression at the post-transcriptional level by silencing targeting mRNA(s). Intriguingly, miRNAs have been implicated in the pathogenesis of both IBD and neurodegenerative diseases (NDDs). miRNAs have emerged as important regulators of gut and blood–brain barrier (BBB) integrity.3 4 Complementing these findings, we recently found significantly upregulated miR-23a-3p and miR-150-5 p in the blood of patients who had undergone successful intestinal microbiota transplantation (IMT) for recurrent Clostridium difficile infection (rCDI).5 Furthermore, we demonstrated the cytoprotective effects of combining these two IMT-regulated miRNAs in intestinal epithelial cell (IEC) …

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    Footnotes

    • Contributors TMM: conceptualisation, writing original draft, critical revision, final approval. PG: production of microRNA-based nanoformulations. CP, AU-K, MF and PG: in vitro experimental lab work on intestinal and neuronal cell lines. CP, DK, MF, AU-K, LC, CA and PG: critical revision, final approval. All the authors have approved the manuscript.

    • Funding This work was partly funded by the Nottingham Digestive Diseases Biomedical Research Centre, University of Nottinghamand the Health and Wellbeing NTU Strategic Research Theme.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.