Excessive Consumption of the Sugar Rich Longan Fruit Promoted the Development of Non-alcoholic Fatty Liver Disease via Mediating Gut Dysbiosis

<title>Abstract</title> <bold><italic>Background: </italic></bold>Controversy exists as towards the association of excessive fruits intake and certain disease risks. Longan is an edible fruit rich in high levels of fructose, glucose and sucrose. The aim of this study was to provide direct evidence on the effect of the sugar rich longan fruit on the development of non-alcoholic fatty liver disease (NAFLD). Chemical profiling of longan fruit was conducted using LC-HRMS and HPLC-ELSD.<bold><italic>Results: </italic></bold>Longan extracts at the doses of 4.0 g/kg, 8.0 and 16.0 g/kg were orally administered for 4 weeks to healthy C57BL/6J mice or to C57BL/6J mice fed with a HFD diet. Fecal microbiome was analyzed by 16S rRNA sequencing. The amounts of short chain fatty acids (SCFAs) in colonic contents were determined by GC-MS. Colon and liver tissues were used for histopathological examination after H&amp;E, Masson’s trichrome, and Oil-red O staining. ELISA method was used for biochemical analysis in serum. In mice fed a normal diet, repeated longan intake for 4 weeks at excess doses (8 or 16 g/kg), but not the normal dose (4 g/kg), promoted inflammation and gut dysbiosis-like status and reduced short-chain fatty acids (SCFAs) production. In high-fat diet (HFD)-fed mice, longan intake at 4 g/kg hardly influenced the NAFLD development. In contrast, excess longan intake (8 or 16 g/kg) promoted NAFLD pathogenesis, including increased abnormality in hepatic indices, elevated inflammation, and gut permeability associated with more severe liver steatosis and fibrosis. Moreover, the exacerbated pathogenic markers were positively correlated with increased blood sugar, aggravated HFD-associated microbial dysbiosis. <bold><italic>Conclusions:</italic></bold><italic> </italic>Effects mediated by excess longan intake resembled that of equivalent free sugars supplementation, suggesting that high level of free sugars in fruits contributed to the promotion of NAFLD development as demonstrated in case of excessive longan intake.