Tissue communication; Investigating the role of the colon in mediating the metabolic health effects of milk proteins

The principal objective of this thesis was to investigate the role of the colon in mediating the metabolic health effects of the milk protein Whey Protein Isolate (WPI). Chapter 2 is a review article submitted to the journal of nutrition research reviews of the Nutrition Society, which outlines the role of the colon in mediating dietary whey proteins health impacts through the formation of colonic metabolites and different dietary protein intakes and supplementation influence such metabolite formation. The review also identifies similar and different alterations in colonic metabolites across the different dietary protein intakes to conditions whereby there is a change in metabolic state, including bariatric surgery, calorie restriction and late pregnancy. Chapter 3 covers a research paper further investigating a previous study by Nychyk et al 2021, where mice fed different milk proteins, WPI or Casein (CAS) in different quantities, with different fat quantities, differed in their tissue gene expressions, caecum metabolites and gut microbiota composition. The greatest differences and improvement in overall health was found in the mice fed 30% WPI, compared to 30% CAS, on a 55% fat diet. Thus, with a focus on the colon and this dietary combination, metabolomics analysis were performed to further understand how the colon and epididymal adipose tissue (EAT) were responding. Gene expression analysis was performed on the colons, duodenums, brown adipose tissues and epididymal adipose tissues selected tissues and compared across different dietary combinations from the Nychyk study. WPI decreases gene expressions associated with TLR3-IRF3 signalling in the duodenum and brown adipose tissue (BAT), highlighting a potential communication between the duodenum and BAT, as well as identifying a mechanism of WPI ability to reduce inflammation. WPI increases CD36 gene expression, as well as reduces inflammatory lysophosphatidylcholine (LPCs), in the colon and EAT. WPI increases TAGs in the EAT, improving fatty acid storage. Finally, chapter 4 is a final discussion outlying the overall impact of this research in contributing to tackling present challenges we face today including obesity, the development of personalised nutrition, as well as its contribution to future research.