Dietary polyphenols and enteric nematodes interact to modulate gut microbiota-derived metabolites and promote type-1 intestinal immune responses in mice

Polyphenols are phytochemicals commonly found in plant-based diets which have demonstrated immunomodulatory and anti-inflammatory properties. However, whether polyphenols can modulate responses to enteric pathogens at mucosal barriers has not yet been elucidated in detail. Here, we show that proanthocyanidin (PAC) polyphenols interact with gut parasites to influence immune function and gut metabolites. PAC intake induced a type-1 bias in the mucosal immune response during two separate models of enteric nematode infection in mice (Heligmosomoides polygyrus and Trichuris muris). PAC intake during T. muris infection was associated with higher numbers of Th1 cells in mesenteric lymph nodes, enhanced interferon signaling in caecal tissue, and an increased number of adult worms. 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 the activity of PAC. Collectively, our results suggest an inter-relationship between a phytonutrient and infection, whereby PAC may augment parasite-induced inflammation, and infection may abrogate the beneficial effects of health-promoting phytochemicals.