Lunularin, a specific gut metabolite of resveratrol, shows marked interindividual variability in production, with individuals divided into "lunularin producers" (LPs) and "non-producers" (LNPs); however, the regulatory factors remain unclear. This study recruited 104 healthy young Chinese adults, integrating dietary questionnaires, microbiomics, and metabolomics to explore the distribution of lunularin metabotypes and their key correlates. Results showed that only 20.2% of participants were LPs, a proportion significantly lower than that reported in European populations. The high-sugar, high-fat dietary pattern correlated negatively with lunularin production and positively with the abundances of Lachnoclostridium and Enterocloster. Multi-omics analyses revealed distinct differences in gut microbiota and metabolic profiles between the two phenotypes: LPs were specifically enriched in Anaerobutyricum, Collinsella (positively correlated with lunularin levels), etc., while Fusobacterium was more abundant in LNPs. Differential metabolites were predominantly enriched in pathways including lactose synthesis and glycolysis, with glucose 1-phosphate and 8-deoxylactucin upregulated in LPs and correlating with specific genera. These findings suggest lunularin production is comprehensively regulated by "diet-microbiota-host metabolism" crosstalk, thereby providing multi-omics evidence for understanding interindividual differences in polyphenol metabolism.
Zhang et al. (Thu,) studied this question.