Ameliorative Effects of Anthocyanin Metabolites on Western Diet-Induced NAFLD by Modulating Co-Occurrence Networks of Gut Microbiome.

Anthocyanins (Acn) have been reported to have preventive effects on Western diet (WD)-induced non-alcoholic fatty liver disease (NAFLD). However, the amount of Acn that reached the bloodstream were less than 1%, suggesting that anthocyanin metabolites (Acn-M) in the gut may contribute to their in vivo effects. This study is focused on a gut microbiota investigation to elucidate the effect of two major Acn-M, protocatechuic acid (PC) and phloroglucinol carboxaldehyde (PG), on NAFLD prevention. C57BL/6N male mice were divided into five groups and fed with a normal diet (ND), WD, WD + 0.5% PC, WD + 0.5% PG and WD + a mixture of 0.25% PC + 0.25% PG (CG) for 12 weeks. The results revealed that WD-fed mice showed a significant increase in final body weight, epididymis fat weight, liver weight and fat accumulation rate, serum total cholesterol, alanine aminotransferase, monocyte chemoattractant protein 1, and 2-thiobarbituric acid reactive substances. At the same time, these indices were significantly decreased by Acn-M in the order of PG, CG > PC. In particular, PG significantly decreased serum glucose and insulin resistance. Gut microbiome analysis revealed that PG significantly increased the relative abundance of , , / ratio, and upregulated glucose degradation pathway. Interestingly, the co-occurrence networks of and in the PC and PG groups were similar to the ND group and different to WD group. These data suggest that PC and PG were able to recover the gut microbiome networks and functions from dysbiosis caused by WD. Therefore, PG might act as a master metabolite for anthocyanins and prevent WD-induced NAFLD and gut dysbiosis.