Lunularin Producers versus Non-producers: Novel Human Metabotypes Associated with the Metabolism of Resveratrol by the Gut Microbiota

[Image: see text] We describe here for the first time the consistent observation of two metabotypes associated with resveratrol metabolism by the human gut microbiota, that is, lunularin (LUNU)-producers and LUNU non-producers. In healthy volunteers (n = 195), resveratrol was reduced to dihydroresveratrol, which only in the LUNU-producer metabotype was sequentially dehydroxylated at the 5-position to yield LUNU and the 3-position to produce 4-hydroxydibenzyl. These metabolites (also 3,4′-dihydroxy-trans-stilbene in some LUNU-producers) were detected in the urine and (or) feces of 74% of volunteers after consuming resveratrol, while 26% lacked these dehydroxylase activities. The LUNU non-producer metabotype was more prevalent in females (P < 0.05) but independent of individuals’ BMI and age. A 4-styrylphenol reductase in both metabotypes converted stilbenes to their corresponding dibenzyls, while no 4-dehydroxylation in stilbenes or dibenzyls was observed. 4-Hydroxy-trans-stilbene, pinosylvin, dihydropinosylvin, 3-hydroxydibenzyl, and 3-hydroxy-trans-stilbene were not detected in vivo or in vitro. Further research on LUNU metabotypes, their associated gut microbiota, and their impact on health is worthwhile.