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EASTBIO: Gut microbiota mediates distinct metabolic effects through dietary fibre fermentation.

  • Full or part time
    Dr A Ross
    Prof P Morgan
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Supervisors:

Dr Alexander Ross (University of Aberdeen)
https://www.abdn.ac.uk/rowett/research/alexander-ross.php

Professor Peter Morgan (University of Aberdeen)
https://www.abdn.ac.uk/rowett/research/peter-morgan.php

Aim:
Increasing evidence suggests that the gut microbiota plays an important role in beneficial effects of nutrition. In part these health benefits may be mediated by dietary fibre fermentate produced by host bacteria. The objective is to understand how different types of dietary fibres can deliver distinct metabolic benefits to the host.

Hypothesis:
The soluble dietary fibre, pectin, promotes the growth and activity of specific gut microbiota, and fermentate that can direct the metabolic response of the host, in favour of lean mass accretion and reduced adiposity.

Background:
Global trends in adult BMI between 1974 and 2014 show steady increases in obesity and it remains a priority public health concern (1). The major health consequences associated with obesity include elevated risks of developing co-morbidities such as type 2 diabetes and cardiovascular disease.

Recent work on gut microbiota has ignited renewed interest in the role of the gut in combating the development of obesity. The way that food triggers mechanisms in the gut is particularly important in this regard. Recent evidence shows that dietary fibre can reduce intake and adiposity substantially (2). A remarkable finding has been that the fibre, pectin, appears to preserve lean body mass, while more weight is lost as fat.

Thus certain fibres may have beneficial metabolic effects over others, which could be exploited for improved foods with better knowledge and understanding.

Approach:
Results indicate that gut microorganisms degrade dietary fibre to produce products that signal via the gut to alter gene expression in the liver.

The project will explore signalling mechanisms from the gut to the liver to improve our understanding of how dietary fibres can influence beneficial fat and lean partitioning. This will build on our data already available on gene expression from Next Generation Sequencing (NGS) following fibre-feeding to rats.

Through NGS of liver mRNA, many genes showed expression levels significantly influenced by dietary fibre type. Several were secreted and potentially important in communication with the brain or fat. Multiple relevant Go ontology terms and Kegg pathways were significantly enriched.

How cells communicate to alter metabolism will be studied mainly in cells of the gut and liver. Dietary fibre will be fermented in vitro using specific fibre-degrading bacteria to generate fermentates for use as cell stimulants. The project will then investigate responses of cultured gut cells or organoids, focusing on secreted cytokines and identification of the active fibre metabolites.

In liver studies, pathways involved in regulating expression of identified target genes in cultured cells or stored tissue will be explored, where possible using agonists, antagonists, and transgenic approaches. Study of the effects of these manipulations on adipose tissues will also be important.

Training in microbiology, cell culture, Next Generation Sequencing, Real-time PCR, Western blotting.

Application Procedure:
http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO application form, along with academic transcripts and CV to Alison McLeod at . Two references should be provided by the deadline using the EASTBIO reference form. Please advise your referees to return the reference form to .

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership. This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body. Queries on eligibility? Email Alison McLeod ().

Candidates should have (or expect to achieve) a minimum of a First Class Honours degree in a relevant subject. Applicants with a minimum of a 2:1 Honours degree may be considered provided they have a Distinction at Masters level.

References

1. The Lancet387:1377-96

2. Adam CL, Williams PA, Dalby MJ, Garden K, Thomson LM, et al. 2014. Nutr. Metab (Lond) 11:36



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