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Precision Medicine DTP - The Oral-Gut Microbiome Axis in Crohn’s disease and Ulcerative Colitis


College of Medicine and Veterinary Medicine

About the Project

Inflammatory Bowel Diseases (IBD) are chronic immune-mediated conditions affecting the gastrointestinal tract. They are very common, with a global prevalence approaching 20-30 million individuals by 2025. The gut microbiome is a critical factor in the development of IBD. There are now several approaches that are aimed at manipulating the gut flora as therapy including faecal transplantation, probiotics and selective expansion of beneficial bacteria populations using spore technologies. However, we do not have the Precision Medicine tools to refine our understanding of the complex gut microbiome, their inter-connection with IBD disease activity to improve the way we choose and tailor microbial-based treatments.

New studies suggest that inflammation may begin in the oral cavity and spread to the gut as pathobionts move between those body sites 1. Hence there is a need to investigate the oral-gut microbiome axis in IBD.

This proposal brings together 4 key PIs with unique expertise:

Gwo-Tzer Ho who leads a large multi-omic IBD cohort study (www.musicstudy.uk) with prospective longitudinal tracking of adult and children with IBD.
Mick Watson who leads a deep metagenomics program with aligned bioinformatic expertise in microbiome analysis capability.
Kostas Gerasimidis who leads a large interventional dietary research in Glasgow with well-characterised patient cohorts with metagenomic/metabolomic data and aligned informatics capability.
David Wilson who leads the Paediatric IBD research in Edinburgh, with patient cohorts with oral and upper digestive tract IBD.

Together, we will use strain level metagenomics to look at cross-talk between the oral and gut microbiome in IBD, and functional metagenomics to look at functional correlates with disease progression/outcome. At a functional level, we will investigate the mobile-ome (such as plasmids, phage), their transmission between the oral cavity and the gut, and their role in disease. With paired oral-stool samples and matched blood samples (and gut tissue) available from MUSIC cohort, we will be able to look at measures of inflammation and develop a mechanistic understanding of which microbes, microbial proteins and metabolites may be causing inflammation; with matched metabolomics we will be able to investigate the effect of diet and microbiome on disease and outcome. The power of metabolomics will be increased by our access to metagenomic data, which will reveal the genes which encode for metabolism in the gut.

This MRC programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.

All applications should be made via the University of Edinburgh, irrespective of project location. For those applying to a University of Glasgow project, your application along with any supporting documents will be shared with University of Glasgow.

http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=919

Please note, you must apply to one of the projects and you must contact the primary supervisor prior to making your application. Additional information on the application process is available from the link above.

For more information about Precision Medicine visit:
http://www.ed.ac.uk/usher/precision-medicine

Funding Notes

Start: September 2021

Qualifications criteria: Applicants applying for an MRC DTP in Precision Medicine studentship must have obtained, or will soon obtain, a first or upper-second class UK honours degree or equivalent non-UK qualification, in an appropriate science/technology area. The MRC DTP in Precision Medicine grant provides tuition fees and stipend of at least £15,285 (UKRI rate 2020/21).

Full eligibility details are available: View Website

Enquiries regarding programme:

References

1. Ray, K. The oral–gut axis in IBD. Nature Reviews Gastroenterology and Hepatology (2020) doi:10.1038/s41575-020-0346-0.

2. Sunkara, T., Rawla, P., Ofosu, A. & Gaduputi, V. Fecal microbiota transplant – a new frontier in inflammatory bowel disease. Journal of Inflammation Research vol. 11 321–328 (2018).

3. DeFilipp, Z. et al. Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant. N. Engl. J. Med. 381, 2043–2050 (2019).

4. Almeida, A. et al. A unified catalog of 204,938 reference genomes from the human gut microbiome. Nat. Biotechnol. 1–10 (2020) doi:10.1038/s41587-020-0603-3.

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