TitleImprovements in Metabolic Syndrome by Xanthohumol Derivatives Are Linked to Altered Gut Microbiota and Bile Acid Metabolism.
Publication TypeJournal Article
Year of Publication2020
AuthorsZhang Y, Bobe G, Revel JS, Rodrigues RR, Sharpton TJ, Fantacone ML, Raslan K, Miranda CL, Lowry MB, Blakemore PR, Morgun A, Shulzhenko N, Maier CS, Stevens JF, Gombart AF
JournalMol Nutr Food Res
Date Published2020 01

SCOPE: Two hydrogenated xanthohumol (XN) derivatives, α,β-dihydro-XN (DXN) and tetrahydro-XN (TXN), improved parameters of metabolic syndrome (MetS), a critical risk factor of cardiovascular disease (CVD) and type 2 diabetes, in a diet-induced obese murine model. It is hypothesized that improvements in obesity and MetS are linked to changes in composition of the gut microbiota, bile acid metabolism, intestinal barrier function, and inflammation.

METHODS AND RESULTS: To test this hypothesis, 16S rRNA genes were sequenced and bile acids were measured in fecal samples from C57BL/6J mice fed a high-fat diet (HFD) or HFD containing XN, DXN or TXN. Expression of genes associated with epithelial barrier function, inflammation, and bile acid metabolism were measured in the colon, white adipose tissue (WAT), and liver, respectively. Administration of XN derivatives decreases intestinal microbiota diversity and abundance-specifically Bacteroidetes and Tenericutes-alters bile acid metabolism, and reduces inflammation. In WAT, TXN supplementation decreases pro-inflammatory gene expression by suppressing macrophage infiltration. Transkingdom network analysis connects changes in the microbiota to improvements in MetS in the host.

CONCLUSION: Changes in the gut microbiota and bile acid metabolism may explain, in part, the improvements in obesity and MetS associated with administration of XN and its derivatives.

PubMed ID31755244
PubMed Central IDPMC7029812
Grant ListS10 RR027878 / RR / NCRR NIH HHS / United States
R01 DK103761 / DK / NIDDK NIH HHS / United States
R01 AT009168 / AT / NCCIH NIH HHS / United States