Introducing Gordonibacter urolithinfaciens into Gut Ecosystems to Study Its Role in Mediating the Metabolic Benefits of Dietary Polyphenols

Abstract Objectives Dietary polyphenols such as ellagitannins undergo microbial conversion to yield urolithins, which improve insulin sensitivity. However, feeding ellagic acid-containing foods sometimes yields variable levels of metabolic improvements in humans, suggesting that some individuals may not harbor the specific microbes responsible for transforming ellagic acid (EA) into urolithins. One species of gut bacteria, Gordonibacter urolithinfaciens (G. uro), has been shown to convert EA into urolithins in vitro. However, the specific role of G. uro in mediating the metabolic benefits of EA-containing foods in vivo is unknown, in part, because of challenges associated with its engraftment in mouse models. This study aimed to determine whether G. uro could be introduced into an established microbiota as a single dose or daily probiotic to facilitate future studies regarding its role in improving host metabolism via conversion of EA to urolithins. Methods Germ-free (GF) C57BL/6 mice were either: (1) mono-associated with G. uro for 2 wks prior to introduction of one of three conventional mouse microbiotas naturally deficient for G. uro, (2) colonized with both G. uro and a conventional G. uro-deficient microbiota together, (3) colonized with a conventional G. uro-deficient microbiota for 2 wks and then given a single oral gavage of G. uro, or (4) colonized with a conventional G. uro-deficient microbiota for 2 wks and then administered G. uro fresh daily in drinking water. Results G. uro successfully monocolonized a previously GF mouse but was not detectable following introduction of a complex G. uro-deficient microbiota. G. uro also failed to persist when GF mice were first colonized with a conventional G. uro-deficient microbiota and then given a single gavage of G. uro. However, ex-GF mice colonized with a complex G. uro-deficient microbiota and given daily doses of G. uro in their drinking water were able to maintain this organism throughout the study. Conclusions Our studies demonstrate the challenges associated with introducing G. uro into a microbiota even when G. uro is provided prior to microbiota establishment and the microbiota is naturally devoid of G. uro. These results suggest that G. uro may need to be administered as a daily probiotic to provide health benefits to individuals unable to convert ellagic acid foods into beneficial urolithins. Funding Sources USDA NIFA.