High sucrose diet-induced dysbiosis of gut microbiota promotes fatty liver and hyperlipidemia in rats

• DOI: 10.1016/j.jnutbio.2021.108621
• Publication Date: 2021-03-09T06:20:17Z
• Authors: Shumin Sun; Yuki Araki; Fumiaki Hanzawa; Miki Umeki; Takaaki Kojima; Naomichi Nishimura; Saiko Ikeda; Satoshi Mochizuki; Hiroaki Oda
• Keywords: Dietary Sucrose; Hyperlipidemia; Dysbiosis; Lipogenesis

Excess sucrose intake has been found to be a major factor in the development of metabolic syndrome, especially in promoting nonalcoholic fatty liver disease. The excess fructose is believed to targets the liver to promote de novo lipogenesis, as described in major biochemistry textbooks. On the contrary, in this study, we explored the possible involvement of gut microbiota in excess sucrose-induced lipid metabolic disorders, to validate a novel mechanism by which excess sucrose causes hepatic lipid metabolic disorders via alterations to the gut microbial community structure. Wistar male rats were fed either a control starch diet or a high-sucrose diet for 4 weeks. Half of the rats in each group were treated with an antibiotic cocktail delivered via drinking water for the entire experimental period. After 4 weeks, rats fed with the high-sucrose diet showed symptoms of fatty liver and hyperlipidemia. The architecture of cecal microbiota was altered in rats fed with high-sucrose diet as compared to the control group, with traits including increased ratios of the phyla Bacteroidetes/Firmicutes, reduced α-diversity, and diurnal oscillations changes. Antibiotic administration rescued high-sucrose diet-induced lipid accumulation in the both blood and liver. Levels of two microbial metabolites, formate and butyrate, were reduced in rats fed with the high-sucrose diet. These volatile short-chain fatty acids might be responsible for the sucrose-induced fatty liver and hyperlipidemia. Our results indicate that changes in the gut microbiota induced by a high-sucrose diet would promote the development of nonalcoholic fatty liver disease via its metabolites, such as short-chain fatty acids.