VALGUT

: phenyl-γ-valerolactones are microbiota-derived compounds that can impact gut health

Abstract

(Poly)phenols are a large class of plant secondary metabolites and the flavan-3-ols are the main flavonoid sub-group, which are present in a plethora of foods, such as cocoa. These compounds undergo extensive structural modification, and, in the colon, they are further catabolised by the gut microbiota to produce characteristic metabolites, known as phenyl-γ-valerolactones (PVLs) and phenylvaleric acids (PVAs). The aims of this thesis were to analyse the beneficial effects of flavan-3-ols and their metabolites at colonic level and assess their bi-directional interaction with the gut microbiota. A literature review critically evaluated how these compounds have potential to maintain, protect, and restore a functional gut barrier. Secondly, the inter-individual and time-dependent changes of the (poly)phenolic composition were observed during faecal fermentation of ileal fluids enriched in cocoa flavan-3-ols. The 5-(3'-hydroxyphenyl)-γ-valerolactone and the 5-(3',4'-dihydroxyphenyl)-γ-valerolactone were within the main products of this ex vivo gut microbial catabolism and higher Bacteroidetes content and a decrease in Erysipelotrichia and Clostridia were observed after 24-hour fermentation. In addition, the microbial catabolism of sulphated forms of (epi)catechins was suggested leading to sulphated PVL and PVA with possible involvement of sulphidogenic microbial species. Moreover, the degree of polymerisation of a cocoa procyanidins extract remained relatively stable during an in vitro 24-h faecal fermentation, although PVLs and PVAs production occurred. Finally, ileal fluid fermentate containing cocoa flavan-3-ols and their characteristic PVLs metabolites were not cytotoxic for caco-2 colonic cells in vitro and degradation of pure PVLs was reported over a 24-h incubation in the cell culture media. To conclude, this thesis has contributed significantly to the understanding of the colonic catabolism of flavan-3-ols and their possible bioactivity within the colon, while sheding further light on commercial and human health implications related to the bioavailability of these flavonoids and their metabolites.

Date of Award	Oct 2023
Original language	English
Sponsors	Department for the Economy
Supervisor	Kirsty Pourshahidi (Supervisor), Nigel Ternan (Supervisor), Chris Gill (Supervisor) & Daniele Del Rio (Supervisor)