Fermented Psidium guajava leaves regulate the gut microbiota and improve metabolic alterations in diabetic mice

The phenolic extract from fermented Psidium guajava leaves (PFGL) helps to improve diabetes; however, its hypoglycemic and hypolipidemic mechanisms remain unclear. In this study, gut microbiota modulation and glucose-lipid metabolism was investigated. The results showed that dietary supplement of PFGL enriched in quercetin glucosides significantly improved serum glucose-lipid profiles as well as insulin resistance in diabetic mice. The gut microbiota of diabetic mice was modulated by PFGL (200 mg/kg), causing an abundance of Bacteroidetes , Prevotellaceae, and Alistipes and a reduced the presence of Firmicutes and Streptococcus . Increased levels of short-chain fatty acids (SCFA) activated G protein-coupled receptor signaling that induced peptide YY release to promote insulin secretion. Diabetes-induced serum metabolite disorders that are involved in glycerophospholipid metabolism and tryptophan metabolism were restored by PFGL. The protein expression of metabolic enzymes including phospho-adenosine 5’-monophosphate-activated protein kinase, fatty acid synthase, acyl-coenzyme A oxidase, and diacylglycerol aeyltransferase 2 were also regulated to promote glucose-lipid metabolism. In particular, gut microbiota enriched with Alistipes genera and SCFA metabolic regulation were closely correlated with diabetes-related indicators. These findings provide a theoretical support for the development and application of PFGL for the treatment of diabetes.