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Mol Nutr Food Res. 2019 Nov 22:e1900789. doi: 10.1002/mnfr.201900789. [Epub ahead of print]

Improvements in Metabolic Syndrome by Xanthohumol Derivatives are Linked to Altered Gut Microbiota and Bile Acid Metabolism.

Author information

1
Linus Pauling Institute, Oregon State University, Corvallis, Oregon, 97331, USA.
2
School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, 97331, USA.
3
Department of Animal Sciences, Oregon State University, Corvallis, Oregon, 97331, USA.
4
Department of Chemistry, Oregon State University, Corvallis, Oregon, 97331, USA.
5
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon, 97331, USA.
6
Department of Microbiology, Oregon State University, Corvallis, Oregon, 97331, USA.
7
Department of Statistics, Oregon State University, Corvallis, Oregon, 97331, USA.
8
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, 97331, USA.
9
College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, 97331, USA.

Abstract

SCOPE:

We previously showed that 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. We hypothesized that improvements in obesity and MetS are linked to changes in the composition of the gut microbiota, bile acid metabolism, intestinal barrier function and inflammation.

METHODS AND RESULTS:

To test this hypothesis, we sequenced 16S rRNA genes and measured bile acids in fecal samples from C57BL/6J mice fed a high-fat diet (HFD) or HFD containing XN, DXN or TXN. We measured the expression of genes associated with epithelial barrier function, inflammation, and bile acid metabolism, in the colon, white adipose tissue (WAT), and liver, respectively. Administration of XN derivatives decreased intestinal microbiota diversity and abundance, specifically Bacteroidetes and Tenericutes, altered bile acid metabolism, and reduced inflammation. In WAT, TXN supplementation decreased pro-inflammatory gene expression by suppressing macrophage infiltration. Transkingdom network analysis connected 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. This article is protected by copyright. All rights reserved.

KEYWORDS:

bile acid; gut microbiota; metabolic syndrome; xanthohumol

PMID:
31755244
DOI:
10.1002/mnfr.201900789

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