Abstract
Gut microbes metabolize the ellagitannin castalagin to ellagic acid and urolithins, a process associated with health effects for the host. Despite the use of the castalagin-rich camu camu extracts in clinical trials, the genes and taxa responsible for castalagin hydrolysis remain elusive. We used multi-omics to discover a castalagin associated hydrolase (cah) operon sparsely distributed in Lachnospiraceae. Analysis of fecal samples from a camu camu supplementation clinical trial demonstrates functional redundancy with prevalence of cah and other ellagic acid metabolism genes in different taxa explaining the prevalence of metabolites. Employing genome mining strategies, we discovered and validated ellagitannin metabolism genes in uncharacterized and uncultured species. We further identified flavogallonic acid as a prevalent metabolite of castalagin in human fecal samples. Collectively, this work provides a genetic basis for castalagin metabolism to urolithins and flavogallonic acid end-metabolites and sets the stage to study the role of metabolism in clinical trials.