TitleXanthohumol Requires the Intestinal Microbiota to Improve Glucose Metabolism in Diet-Induced Obese Mice.
Publication TypeJournal Article
Year of Publication2021
AuthorsLogan IE, Shulzhenko N, Sharpton TJ, Bobe G, Liu K, Nuss S, Jones ML, Miranda CL, Vasquez-Perez S, Pennington JM, Leonard SW, Choi J, Wu W, Gurung M, Kim JP, Lowry MB, Morgun A, Maier CS, Stevens JF, Gombart AF
JournalMol Nutr Food Res
Date Published2021 Nov
KeywordsAnimals, Diet, High-Fat, Flavonoids, Gastrointestinal Microbiome, Glucose, Male, Mice, Mice, Inbred C57BL, Mice, Obese, Propiophenones, RNA, Ribosomal, 16S

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

METHODS AND RESULTS: To test the hypothesis, the study feeds conventional and germ-free male Swiss Webster mice either a low-fat diet (LFD, 10% fat derived calories), a high-fat diet (HFD, 60% fat derived calories), or a high-fat diet supplemented with XN at 60 mg kg body weight per day (HXN) for 10 weeks, and measure parameters of glucose and lipid metabolism. In conventional mice, the study discovers XN supplementation decreases plasma insulin concentrations and improves Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). In germ-free mice, XN supplementation fails to improve these outcomes. Fecal sample 16S rRNA gene sequencing analysis suggests 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 (DXN), 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. The study results warrant future metagenomic studies which will provide insight into complex microbe-microbe interactions and diet-host-microbiota interactions.

Alternate JournalMol Nutr Food Res
PubMed ID34496124
PubMed Central IDPMC8571065
Grant ListR01 AT009168 / AT / NCCIH NIH HHS / United States
S10 RR027878 / RR / NCRR NIH HHS / United States
R01 DK103761 / DK / NIDDK NIH HHS / United States