The role of dietary composition on metabolic health of the gut-liver axis

Mushtaq, Aleena (2021) The role of dietary composition on metabolic health of the gut-liver axis. Doctoral thesis, University of East Anglia.

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Abstract

The critical role of a disrupted gut-liver axis in the pathogenesis of many diseases has only recently been accepted. The role of diets in the related bidirectional relationship between the gut, along with its microbiota, and the liver are however poorly defined. Designing an experimental animal model to study the gut-liver axis requires the use of commercial control diets such as chow or purified low-fat (LF) diets. While chow is a whole foods grain-based diet, LF contains high amount of easily accessible refined carbohydrates together with reduced dietary fibre and resembles a low-fat Western style diet. In this thesis, we compared chow and LF diets to characterise their differential effects on the gut-liver axis with focus on the ileum in C57BL/6J mice. For the first time, we showed that the LF diet significantly increased hepatic triglycerides, ileal bile acid levels and altered the ileal microbiota compared to chow. Long-term consumption of the LF diet led to further increased hepatic triglycerides, reduced ileal expression of antimicrobial peptides and cell cycle related genes. Next, we investigated strategies to prevent the LF induced phenotype by; 1) reducing the consumption of the LF diet with calorie restriction (CR) and, 2) addition of dietary fibres to the LF diet. We found that CR was successfully able to prevent the pathophysiological effects of the LF diet on the gut-liver axis and led to a distinct ileal microbiota profile. The second prevention strategy of enriching the LF diet with dietary fibres reduced the LF induced accumulation of hepatic triglycerides in mice. Moreover, our results showed differential effects of the structurally distinct dietary fibres on the ileal immune related gene expression. Lastly, we characterised the diet induced changes in genetically identical mice obtained from different vendors, to show differential ileal microbiota and bile acid profiles. Our studies highlight that dietary composition and animal source can affect the ileal microbiota composition and function, and lead to significant phenotype variability. The novel results from this thesis indicate that dietary fibres are essential food components with mode of actions not just in the colon but also in the ileum. Our studies further confirm that even low-fat Western style diets may have a pathophysiological impact on human health if the diet is depleted in essential food components such as dietary fibres.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Chris White
Date Deposited: 07 Jun 2021 13:00
Last Modified: 07 Jun 2021 13:00
URI: https://ueaeprints.uea.ac.uk/id/eprint/80209
DOI:

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