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

Polyphenols 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 roundworm Heligmosomoides polygyrus, and induced a type-1, interferon-driven mucosal immune response during infection with the large intestinal whipworm Trichuris muris. PAC also induced alterations in mesenteric lymph node T-cell populations that were dependent on infection model, with a Th2/Treg bias during H. polygyrus infection, and a Th1 bias during T. muris infection. In the absence of infection, PAC intake promoted the expansion of Turicibacter sp. within the gut microbiota, increased faecal short chain fatty acids, and enriched phenolic metabolites such as phenyl-gamma-valerolactones in the caecum. However, these putatively beneficial effects were reduced in PAC-fed mice infected with T. 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 dwelling T. muris), and infection may abrogate the beneficial effects of health-promoting phytochemicals. ### Competing Interest Statement The authors have declared no competing interest.