Xanthohumol requires the intestinal microbiota to mediate its benefits. - GreenMedInfo Summary

SCOPE: The polyphenol xanthohumol (XN) improves dysfunctional glucose and lipid metabolism in diet-induced obesity animal models. Because XN changes intestinal microbiota composition, we hypothesized that XN requires the microbiota to mediate its benefits.

METHODS AND RESULTS: To test our hypothesis, we fed conventional and germ-free male Swiss Webster mice either a low-fat diet (10% fat derived calories), a high-fat diet (60% fat derived calories), or a high-fat diet supplemented with XN at 60 mg/kg body weight per day for 10 weeks, and measured parameters of glucose and lipid metabolism. In conventional mice, we discovered XN supplementation decreased plasma insulin concentrations and improved Homeostatic Model Assessment of Insulin Resistance. In germ-free mice, XN supplementation failed to improve these outcomes. Fecal sample 16S rRNA gene sequencing analysis suggested XN supplementation changes microbial composition and dramatically alters the predicted functional capacity of the intestinal microbiota. Furthermore, the intestinal microbiota metabolizes XN into bioactive compounds, including dihydroxanthohumol, an anti-obesogenic compound with improved bioavailability.

CONCLUSION: XN requires the intestinal microbiota to mediate its benefits, which involves complex diet-host-microbiota interactions with changes in both microbial composition and functional capacity. Our results warrant future metagenomic studies, which will provide insight into complex microbe-microbe interactions, and diet-host-microbiota interactions. This article is protected by copyright. All rights reserved.