Gut microbial-mediated polyphenol metabolism is restrained by parasitic whipworm infection and associated with altered immune function in mice

Abstract

AbstractPolyphenols are phytochemicals commonly found in plant-based diets which have demonstrated immunomodulatory and anti-inflammatory properties. However, the interplay between polyphenols and pathogens at mucosal barrier surfaces has not yet been elucidated in detail. Here, we show that proanthocyanidin (PAC) polyphenols interact with gut parasites to influence immune function and gut microbial-derived metabolites in mice. PAC intake inhibited mastocytosis during infection with the small intestinal roundwormHeligmosomoides polygyrus, and induced a type-1, interferon-driven mucosal immune response during infection with the large intestinal whipwormTrichuris muris.PAC also induced alterations in mesenteric lymph node T-cell populations that were dependent on infection model, with a Th2/Treg bias duringH. polygyrusinfection, and a Th1 bias duringT. murisinfection. In the absence of infection, PAC intake promoted the expansion ofTuricibactersp. within the gut microbiota, increased faecal short chain fatty acids, and enriched phenolic metabolites such as phenyl-γ-valerolactones in the caecum. However, these putatively beneficial effects were reduced in PAC-fed mice infected withT. muris,suggesting concomitant parasite infection can attenuate gut microbial-mediated PAC catabolism. Collectively, our results suggest an inter-relationship between a phytonutrient and infection, whereby PAC may augment parasite-induced inflammation (most prominently with the caecum dwellingT. muris), and infection may abrogate the beneficial effects of health-promoting phytochemicals.