Gut microbiome-mediated transformation of dietary phytonutrients is associated with health outcomes.

Food, especially plant-based diet, has complex chemical diversity. However, large-scale phytonutrient-metabolizing activities of gut bacteria are largely unknown. Here we integrated and systematically analysed multiple databases containing information on enzymatic reactions and food health benefits, and 3,068 global public human microbiomes. Transformation of 775 phytonutrients from edible plants was associated with enzymes encoded by diverse gut microbes. In vitro assays validated the biotransformation activity of gut species, for example, Eubacterium ramulus. The biotransformation of phytonutrients demonstrated high interpersonal and geographical variability. Machine learning models based on 2,486 public case-control microbiomes, using the abundances of enzymes associated with modification of phytonutrients present in health-associated foods, discriminated the health status of individuals in multiple disease contexts, suggesting altered biotransformation potential in disease. We validated the association of microbiome-encoded enzymes with the anti-inflammatory activity of common edible plants by combining metagenomics and metatranscriptomics analysis in specific-pathogen-free and germ-free mice. These findings have implications for designing precise, personalized diets to guide an individual towards a healthy state.