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Xanthohumol Requires the Intestinal Microbiota to Improve Glucose Metabolism in Diet‐Induced Obese Mice
Author(s) -
Logan Isabelle E.,
Shulzhenko Natalia,
Sharpton Thomas J.,
Bobe Gerd,
Liu Kitty,
Nuss Stephanie,
Jones Megan L.,
Miranda Cristobal L.,
VasquezPerez Stephany,
Pennington Jamie M.,
Leonard Scott W.,
Choi Jaewoo,
Wu Wenbin,
Gurung Manoj,
Kim Joyce P.,
Lowry Malcolm B.,
Morgun Andrey,
Maier Claudia S.,
Stevens Jan F.,
Gombart Adrian F.
Publication year - 2021
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202100389
Subject(s) - gut flora , xanthohumol , biology , bioavailability , lipid metabolism , calorie , obesity , insulin resistance , dysbiosis , metabolism , endocrinology , food science , biochemistry , pharmacology , ecology , key (lock)
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 −1 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.