Network biology approaches to study the crosstalk between bifidobacteria, immune cells and the intestinal epithelium.

Treveil, Agatha (2020) Network biology approaches to study the crosstalk between bifidobacteria, immune cells and the intestinal epithelium. Doctoral thesis, University of East Anglia.

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Abstract

The intestinal epithelial cell (IEC) barrier represents a key interface between host immune cells and commensal microbes. Communication between these compartments is crucial to maintenance of gut homeostasis by protecting against pathogens, maintaining a balance of commensal microbes and preventing overactivation of inflammation. A mechanistic understanding of how these compartments communicate with and respond to each other is crucial for developing preventative measures and treatments for complex gut dysbiosis, such as observed in inflammatory bowel disease(IBD).In this thesis I sought to study interactions between the health-promoting bacterial genus Bifidobacterium, the intestinal epithelium and the immune system to gain understanding about this complex system. To do this, I complemented experimental approaches with computational methods such as molecular interaction networks, to investigate inter-and intra-cellular molecular regulation at a systems level.

Using transcriptomics data from small intestinal organoid models enriched for specific epithelial cell types, I showed that Paneth cells and goblet cells exhibit shared and unique transcriptional and post-transcriptional regulation. Meanwhile, I highlighted a possible connection between IBD and IECs at the regulatory level. Further extending the study of IBD, I investigated the effect of IBD-relevant cytokines on IECs, shedding light on the causes of non-response to anti-cytokine treatments and presenting a potential new candidate for therapeutic targeting. Additionally, given the role of bifidobacteria in promoting gut health, myself and colleagues sought to define the impact of bifidobacteria on IECs of different aged mice and to study their interaction with macrophages at a molecular level.

Overall, this multidisciplinary work has increased mechanistic understanding of the interplay between IECs, immune cells and commensal microbes, while demonstrating the use of networks for such studies. This should ultimately lead to a better understanding of gut homeostasis and drive development of targeted approaches for prevention and treatment of gut dysbiosis related disorders.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	16 Feb 2021 09:02
Last Modified:	16 Feb 2021 09:02
URI:	https://ueaeprints.uea.ac.uk/id/eprint/79261
DOI:

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