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The effects of gut microbiome metabolites in modulating enteroendocrine cell function and gut hormone secretion

School of Biological Sciences | PHD
Funding
Unfunded
Reference Number
SBIO-2020-1092
Application Deadline
None specified
Start Date
None specified

Overview

Enteroendocrine cells are the most abundant endocrine cell-type in the human body. These are specialised gastrointestinal cells secreting hormones into either the circulation (for systemic actions), the extracellular space (for paracrine signalling), or to the enteric nervous system (for stimulation of nerve endings). The lumen of the gastrointestinal tract is colonised by a diverse range of highly mutualistic microbiota which have various effects on the development and function of the gut-specific immune system. There is some information to suggest that the microbiota interact with enteroendocrine cells but the mechanisms appear complex and at present are poorly understood.

Microbiota-enteroendocrine crosstalk may involve the production of multiple bioactive small molecule metabolites which are either directly produced by the gut microbiota or by the metabolism of dietary components. This PhD project will investigate how commensal bacteria regulate the production of metabolites, and how these microbiota-derived products influence the function of several enteroendocrine cell types and the secretion.

After careful literature review a comprehensive list of important microbial metabolites will be drawn up, the compounds will be obtained and screened and their cytological actions on enteroendocrine cell lines using techniques such as tissue culture and High Content Analysis. The various compounds will likely be the microbial breakdown products of polysaccharides, tryptophan, bile acids, arginine and histidine, but they could extend to recently discovered microbial metabolites occurring in vegetarian, carnivorous or mixed diets. The project will then undertake detailed mechanistic studies to investigate how metabolites interact with cells and their probable synergistic effects in regulating hormone secretion and human metabolite.

Project Summary
Supervisor

Professor Brian Green

Research Profile


Mode of Study

Full-time: 3 years


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