The Gut Microbiome and Diet Interact to Dictate Personalized Response to Broccoli Sprout Consumption

Broccoli sprouts produce sulforaphane (SFN), a dietary isothiocyanate with anti-cancer and anti-inflammatory properties. Human intervention trials observe large variation in metabolite generation and bioactivity with broccoli sprout consumption across individuals. We hypothesize that interactions between pre-intervention diet and personalized gut microbiome composition contribute to this variation. This exploratory analysis leverages a small existing dataset to test novel mediation pathways, with the goal of identifying associations for future validation in larger, prospectively designed studies. In a trial of 38 healthy adults, we analyzed participant-recorded 7-day food diaries, profiled baseline gut microbiome compositions, and quantified urinary SFN metabolites over 72 h after broccoli sprout consumption. Using regression-based mediation analysis, we modeled two complementary predictions: (1) that specific gut bacterial genera mediate how pre-intervention diet composition influences SFN metabolism, and (2) that particular dietary components mediate how gut microbiome composition influences SFN metabolism. These analyses found that seven genera, including Collinsella, Ruminococcus, and Bifidobacterium, mediated relationships between pre-intervention diet and SFN metabolites, particularly the bioactive forms. Unsupervised clustering further revealed three distinct baseline gut microbiome community "types," each exhibiting differential production of SFN-nitrile, a biologically inert metabolite, with effects mediated by the consumption of specific carbohydrate classes. Together, these findings indicate that microbiome structure, in concert with diet, shapes individual SFN metabolic outcomes. Considering pre-intervention diet and gut microbiome may therefore enhance the design and personalization of cruciferous vegetable interventions.