Shatianyu (Citrus grandis L. Osbeck) Flavonoids and Dietary Fiber in Combination Are More Effective Than Individually in Alleviating High-Fat-Diet-Induced Hyperlipidemia in Mice by Altering Gut Microbiota

This study was aimed at exploring the separate and combined anti-hyperlipidemic effect of Shatianyu (Citrus grandis L. Osbeck) flavonoids (SPFEs) and DF (SPDF) on HFD-fed mice after 14-week administration in diet, together with the possible microbiota-mediated mechanisms. SPFEs and SPDF were more effective together than separately in improving serum lipid profiles, decreasing hepatic lipid accumulation, and upregulating the expression of hepatic CPT1a, CYP7A1, ABCG5, and ABCG8. Butyrate has been previously proved to have an anti-hyperlipidemic effect. The fecal butyrate contents were negatively correlative with serum/ liver lipid but positively correlated with fecal total bile acids levels, and SPDF + SPFEs had the most fecal butyrate in this study. SPDF or SPFEs enriched microbiota related to acetic and propionic acids production, while SPDF + SPFEs also bloomed norank_f_Muribaculaceae, Dubosiella, Lachnoclostridium, and norank_f_Eubacterium_coprostanoligenes_group, which were positively correlated to fecal butyrate contents. Thus, SPFEs and SPDF might alleviate hyperlipidemia synergistically by regulating microbiota to produce butyrate, thereby regulating lipid metabolism.