Glycolipid Metabolism and Metagenomic Analysis of the Therapeutic Effect of a Phenolics-Rich Extract from Noni Fruit on Type 2 Diabetic Mice

The phenolics of noni fruit possess antihyperglycemic activity; however, the molecular mechanisms remain unclear. To understand the potential effects it has on type 2 diabetes (T2D), the glycolipid metabolism and gut microbiota regulation of phenolic-rich extracts from noni fruit (NFEs) were investigated. The results indicated that NFE could remarkably ameliorate hyperglycemia, insulin resistance, oxidative stress, and glycolipid metabolism via the adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway in T2D mice. Furthermore, metagenomic sequencing results revealed that NFE intervention modulated the gut microbiota composition in T2D mice, characterized by increased abundance of unclassified_o_Bacteroidales, Alistipes, Prevotella, Lactobacillus, and Akkermansia and decreased abundance of Oscillibacter, Desulfovibrio, and significantly decreased the pathways related to carbohydrate metabolism, translation, amino acid metabolism, and nucleotide metabolism. Taken together, the results provided new evidence that the hypoglycemic and hypolipidemic activities of NFE in T2D were likely attributed to the activation of the liver AMPK pathway and modulation of gut microbiota.