Alternations of microRNAs, the microbiome, and gut-host interactions in gastrointestinal diseases

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Yau, T.O. ORCID: 0000-0002-3283-0370, 2022. Alternations of microRNAs, the microbiome, and gut-host interactions in gastrointestinal diseases. PhD, Nottingham Trent University.

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Abstract

Over the past few decades, an ageing population combined with a shift towards a Western lifestyle has predisposed many individuals towards inter-connected gastrointestinal (GI) diseases, including inflammatory bowel disease (IBD), colorectal cancer (CRC), gastric cancer (GC) and Clostridioides difficile (C. difficile) infection (CDI). anti-TNF-α treatment for IBD patients has a high unresponsive rate, by using bioinformatics approaches, I identified neutrophil chemotaxis may contribute to the treatment resistance and IL13RA2 is the best predictor to identify treatment unresponsive patients. On the other hand, in the intestinal tract, colonocytes consistently exfoliate and shed into the lumen, affecting gut microbiota composition. These molecular/microbial changes involved in disease pathogenesis can be detected in faeces. By using Taqman probe-based real-time polymerase chain reaction (RT qPCR) assay, several non-coding microRNAs (such as miR-18a, miR-20a, miR-221 and miR 135b) and gut microbes (including Fusobacterium nucleatum, Parvimonas micra, Gemella morbillorum, Peptostreptococcus anaerobius, Clostridium hathewayi and Lachnoclostrium sp.) are highly expressed/enriched in faeces in CRC individuals compared to control subjects. The use of a faecal immunological test (FIT) in combination with these biomarkers may improve the non-invasive CRC screening accuracy. Furthermore, Epstein-Barr virus (EBV) is an oncogenic virus and EBV-driven GC accounts for roughly 10% of total GC cases. GC cells infected with EBV alter the molecular aspect at whole-genome, transcriptome, and epigenome levels. For instance, AKT2 activated by mutation in EBV-positive GC cells affecting downstream MAPK and focal adhesion signalling pathways; AKT2 mutation associates with poor patient survival in EBV-positive GC. Furthermore, once patients have received GI treatments, it may suppress/interfere with the patients’ immune system, disrupt the gut flora homeostasis and trigger CDI. Faecal microbiota transplantation (FMT) has been demonstrated as an effective and alternative treatment strategy for CDI patients. However, it is still in clinical trials due to safety concerns. My study revealed that serum miRNAs such as miR-23a-3p, miR-150-5p, miR-26b-5p and miR-28-5p could be used to monitor FMT treatment in CDI patients, and these markers inversely correlate with IL-12B, IL-18, FGF21 and TNFSRF9 at serum protein and mRNA levels, respectively. Furthermore, miR-23a and miR-150 showed cytoprotective effects against C. difficile Toxin B (TcdB).

Item Type:	Thesis
Creators:	Yau, T.O.
Date:	August 2022
Rights:	The copyright in this work is held by the author. You may copy up to 5% of this work for private study or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed to the author.
Divisions:	Schools > School of Science and Technology
Record created by:	Jeremy Silvester
Date Added:	02 Jun 2023 11:09
Last Modified:	02 Jun 2023 11:09
URI:	https://irep.ntu.ac.uk/id/eprint/49102