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Am J Physiol Gastrointest Liver Physiol. 2018 Jan 1;314(1):G119-G130. doi: 10.1152/ajpgi.00378.2016. Epub 2017 Oct 12.

Dietary copper-fructose interactions alter gut microbial activity in male rats.

Song M1,2, Li X3, Zhang X4,5,2,6,7, Shi H5, Vos MB8, Wei X4,7, Wang Y9, Gao H10, Rouchka EC3, Yin X4,7, Zhou Z11,12, Prough RA13, Cave MC1,5,2,6,13,14, McClain CJ1,5,2,6,14.

Author information

1
Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine , Louisville, Kentucky.
2
Hepatobiology and Toxicology Center, University of Louisville School of Medicine , Louisville, Kentucky.
3
Bioinformatics Core. University of Louisville School of Medicine , Louisville, Kentucky.
4
Department of Chemistry, University of Louisville School of Medicine , Louisville, Kentucky.
5
Department of Pharmacology and Toxicology, University of Louisville School of Medicine , Louisville, Kentucky.
6
University of Louisville Alcohol Research Center, University of Louisville School of Medicine , Louisville, Kentucky.
7
Center for Regulatory and Environmental Analytical Metabolomics, University of Louisville School of Medicine , Louisville, Kentucky.
8
Department of Pediatrics, Emory University School of Medicine, and Children's Healthcare of Atlanta, Atlanta, Georgia.
9
College of Food Science and Engineering, Jilin Agricultural University , Changchun , China.
10
Genomics Facility, University of Louisville School of Medicine , Louisville, Kentucky.
11
Center for Translational Biomedical Research, University of North Carolina at Greensboro, Kannapolis, North Carolina.
12
Department of Nutrition, University of North Carolina at Greensboro, Kannapolis, North Carolina.
13
Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine , Louisville, Kentucky.
14
Robley Rex Louisville Veterans Afairs Medical Center , Louisville, Kentucky.

Abstract

Dietary copper-fructose interactions contribute to the development of nonalcoholic fatty liver disease (NAFLD). Gut microbiota play critical roles in the pathogenesis of NAFLD. The aim of this study was to determine the effect of different dietary doses of copper and their interactions with high fructose on gut microbiome. Male weanling Sprague-Dawley rats were fed diets with adequate copper (6 ppm CuA), marginal copper (1.5 ppm CuM) (low copper), or supplemented copper (20 ppm CuS) (high copper) for 4 wk. Deionized water or deionized water containing 30% fructose (wt/vol) was given ad libitum. Copper status, liver enzymes, gut barrier function, and gut microbiome were evaluated. Both low- and high-copper diets led to liver injury in high-fructose-fed rats, and this was associated with gut barrier dysfunction, as shown by the markedly decreased tight junction proteins and increased gut permeability. 16S rDNA sequencing analysis revealed distinct alterations of the gut microbiome associated with dietary low- and high-copper/high-fructose feeding. The common features of the alterations of the gut microbiome were the increased abundance of Firmicutes and the depletion of Akkermansia. However, they differed mainly within the phylum Firmicutes. Our data demonstrated that a complex interplay among host, microbes, and dietary copper-fructose interaction regulates gut microbial metabolic activity, which may contribute to the development of liver injury and hepatic steatosis. The distinct alterations of gut microbial activity, which were associated with the different dietary doses of copper and fructose, imply that separate mechanism(s) may be involved. NEW & NOTEWORTHY First, dietary low- and high-copper/high-fructose-induced liver injury are associated with distinct alterations of gut microbiome. Second, dietary copper level plays a critical role in maintaining the gut barrier integrity, likely by acting on the intestinal tight junction proteins and the protective commensal bacteria Akkermansia. Third, the alterations of gut microbiome induced by dietary low and high copper with or without fructose differ mainly within the phylum Firmicutes.

KEYWORDS:

NAFLD; copper; fructose; gut barrier function; gut microbiome

PMID:
29025734
PMCID:
PMC5866377
DOI:
10.1152/ajpgi.00378.2016
[Indexed for MEDLINE]
Free PMC Article

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