Functional diversification of dietary plant small molecules by the gut microbiome

Plants are composed of diverse secondary metabolites (PSMs), which are widely associated with human health. Whether and how the gut microbiome mediates such impacts of PSMs is poorly understood. Here, we show that discrete dietary and medicinal phenolic glycosides, abundant health-associated PSMs, are utilized by distinct members of the human gut microbiome. Within the Bacteroides, the predominant gram-negative bacteria of the Western human gut, we reveal a specialized multi-enzyme system dedicated to the processing of distinct glycosides based on structural differences in phenolic moieties. This Bacteroides metabolic system liberates chemically distinct aglycones with diverse biological functions, such as colonization resistance against the gut pathogen Clostridioides difficile via anti-microbial activation of polydatin to the stilbene resveratrol and intestinal homeostasis via activation of salicin to the immunoregulatory aglycone saligenin. Together, our results demonstrate generation of biological diversity of phenolic aglycone "effector" functions by a distinct gut-microbiome-encoded PSM-processing system.