Comprehensive strain-level characterisation of microbial communities associated with inflammatory bowel disease

Overview

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder driven by complex interactions between environmental, microbial and immune-mediated factors 1,2. An unfavourable shift in gut microbiome composition, known as dysbiosis, is now considered a key feature of IBD 2-5, however it is unclear how specific microorganisms and their interactions with host cells contribute to disease onset and progression.

Previous IBD studies have been largely limited to older sequencing methods with low phylogenetic and functional resolution. Furthermore, these studies have predominantly focused on bacterial populations, while other important elements of intestinal ecology (e.g. viruses and plasmids) remain poorly characterised.

Together, these limitations have prohibited the comprehensive characterisation of microbial perturbations observed in IBD.

Hypothesis

We hypothesise that the compositional and functional organisation of microbial communities in the mucosal lining contribute to the initiation and progression of IBD.

Aims

This project aims to:

• perform strain-level characterisation of microbial communities in epithelial mucosa biopsy samples from individuals with IBD and non-IBD controls.
• apply high-resolution metagenomics – the sequencing and reconstruction of all microbial DNA from an environmental or clinical sample6 – to epithelial mucosa biopsy samples from individuals with and without IBD
• use advanced bioinformatic tools to identify microorganisms – including all bacteria, viruses and plasmids – associated with IBD, along with functions underpinning disease pathogenesis.

Together, these approaches will provide the most comprehensive functional analysis of the intestinal microbiome in IBD to date and will generate fundamental new knowledge on the microbial role in IBD etiology and pathogenesis.

References

1. Xavier, R. J. & Podolsky, D. K. Unravelling the pathogenesis of inflammatory bowel disease. Nature 448, 427-434, doi:10.1038/nature06005 (2007).
2. Imhann, F. et al. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut 67, 108-119, doi:10.1136/gutjnl-2016-312135 (2018).
3. Morgan, X. C. et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol 13, R79, doi:10.1186/gb-2012-13-9-r79 (2012).
4. Halfvarson, J. et al. Dynamics of the human gut microbiome in inflammatory bowel disease. Nat Microbiol 2, 17004, doi:10.1038/nmicrobiol.2017.4 (2017).
5. Pascal, V. et al. A microbial signature for Crohn's disease. Gut 66, 813-822, doi:10.1136/gutjnl-2016-313235 (2017).
6. Tyson, G. W. et al. Community structure and metabolism through reconstruction of microbial genomes from the environment. Nature 428, 37-43, doi:10.1038/nature02340 (2004).

Research activities

Professor Tyson leads a team of experts in the development and application of culture-independent molecular approaches and open-source informatic tools that have revolutionised the field of microbial ecology.

You will receive training in:

• DNA sequencing
• metagenomics
• statistical analyses
• genome annotation.

Outcomes

The key outcomes of the project will be to:

1. Identify bacterial strains, viruses and plasmids that are associated with IBD in epithelial mucosa samples.
2. Examine the functional role of these microorganisms and molecular mechanisms contributing to disease.

Keywords

• microbial ecology
• metagenomics
• medical microbiology
• inflammatory bowel disease
• microbiome
• meta-omics

Contact

Contact the supervisor for more information.