Dietary Fructose Induced Gut Microbiota Dysbiosis is An Early Event in the Onset of Metabolic Phenotype

Abstract

ObjectiveThe increased consumption of sugar‐sweetened beverages (SSBs) parallels the obesity epidemic in the United States. Dietary glucose and fructose induce divergent metabolic effects, with fructose being associated with poor metabolic outcomes. The underlying mechanism(s) remain unclear. The aim of this study is to explore whether dietary fructose and glucose instigate differential alterations of gut microbiome and the effect of short chain fatty acid‐butyrate supplementation on fructose induced alteration of gut mcirobiome.MethodsMale weanling Sprague‐Dawley rats were assigned to six groups: control, 10% glucose, 3% fructose, 10% fructose, 10% fructose plus tributyrin (Tb) and 10% fructose plus glycerol (vehicle control for Tb) (n=8/group). Rats were fed with deionized water or deionized water containing 3% fructose, 10% fructose or 10% glucose (w/v) with ad libitum access to AIN‐93G based normal chow diet for 4 weeks. Tributyrin, a prodrug of butyrate, was supplemented via oral gavage at the dose of 2g/kg body weight three times a week. Glycerol was given equal volume as vehicle control. Calorie intake, liver histology and were evaluated. The fecal microbiome was analyzed by 16S rDNA sequencing.ResultsFour weeks feeding with fructose or glucose did not result in hepatic steatosis and liver injury as shown by liver histology and plasma ALT and AST assay. However, rats fed with 10% fructose exhibited a higher body weight gain and energy efficiency ratio as well as elevated liver weight and liver/body weight ratio compared to rats fed with 10% glucose. 16S rDNA sequencing analysis showed that both 10% fructose and glucose led to a significantly decreased abundance of Firmicutes, elevated Bacteroidetes and Proteobacteria to a similar extent. Moreover, 10% fructose induced alterations of above mentioned gut microbiome can be abrogated by tributyrin supplementation. However, these alterations were not seen in 3% fructose fed rats, suggesting that fructose induced alterations of gut microbiome is related to the amount of fructose intake. In addition, the abundance of Ruminococcaceae and Lachnospiraceae, the major butyrate producers in the order of Clostridia (phylum Firmicutes) which are obligate anaerobes, showed a similar trend of decrease in both 10% fructose and glucose fed rats.ConclusionOur data clearly showed that gut microbiota dysbiosis induced by dietary sugars is an early event prior to the alterations of phenotype, highlighting the crucial role of gut microbiota in the development of metabolic syndrome. Dietary intervention to modulate gut microbiome could be a promising strategy to prevent the disease development.Support or Funding InformationThis study was supported in part by NIH Grants U01AA021901, U01AA022489, R01AA023681, an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM113226 and the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number P50AA024337. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (C.J.M.); the Veterans Administration (C.J.M.); and the Uof L Clinical and Translational Pilot Program (C.J.M.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.