Immuno-modulatory effects of microbial metabolites of flavan-3-ols and dimeric procyanidins

Objective: The gut microbiota is recognised to impact on human immune function, but we still know little about the immuno-modulating abilities of specific metabolites derived from microbiota biotransformation of dietary components. The present research aimed to evaluate the potential of microbially-derived metabolites of flavan-3-ols and dimeric procyanidins on human immune function. Methods: Peripheral blood mononuclear cells from healthy donors were subjected to stimulation with LPS in presence or absence of different microbial polyphenol metabolites. After 5 days, T cell proliferation was measured by means of CFSE staining. IL6 and IL1B gene expression was measured after 4 hours of stimulation by real-time PCR. Results: The results showed the immuno-modulatory potential of flavon-3-ols and procyanidins bacterial metabolites. Hydroxyphenylacetic acid was able to decrease inflammatory gene expression induced by LPS. 3,4-dihydroxyphenylpropionic acid also presented a marked anti-inflammatory capabilities, reducing IL6 and IL1B gene expression and LPS-primed T cell response. Conclusions: Those preliminary data indicate that small phenolic acids produced by the gut microbiota upon biotransformation of complex plant polyphenols display different capabilities to regulate the inflammatory response. This has important implications for measuring the metabolic output of the gut microbiome and for identifying the molecular basis of how foods rich in polyphenols actually mediate their purported health effects in humans.