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

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.

Automated summary

We report the discovery of two metabotypes associated with resveratrol metabolism by the human gut microbiota: LUNU (lunularin) producers and LUNU non-producers. The LUNU-producer metabotype can sequentially dehydroxylate resveratrol to yield LUNU and 4-hydroxydibenzyl, while the LUNU non-producer metabotype lacks this ability. These metabolites were detected in the urine and (or) feces of the majority of volunteers, but around 26% lacked the corresponding enzyme activity. Both metabotypes possess a 4-styrylphenol reductase that converts resveratrol to its corresponding dibenzyl.