Metabolomic insights into the response strategies of bats to high-glucose stimulation

Existing therapeutic options for diabetes remain limited, underscoring the urgent need to explore novel mechanisms for blood glucose regulation. Bats despite diverse dietary habits, making them ideal models for studying hypoglycemic mechanisms. In this study, we performed intraperitoneal glucose tolerance tests (IPGTTs) on five bat species three frugivorous or nectarivorous species (hereafter collectively referred to as frugivorous bats, given the high sugar content of both fruits and nectar) and two insectivorous species. A total of 704 known serum metabolites were analyzed quantitatively using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Compared with insectivorous bats, frugivorous bats exhibited significantly higher levels of amino acid-related metabolites under high-glucose stimulation. These included N-acyl amino acids, aromatic amino acid derivatives, and branched-chain amino acid metabolites, which were enriched significantly in pathways, such as alanine, arginine, and D-amino acid metabolism. Additionally, several known gut-brain axis (GBA) metabolites-such as neurotransmitters, bile acids, and short-chain fatty acids-exhibited strong host dietary and species specificity. Frugivorous bats were enriched in neurotransmitters and short-chain fatty acids associated with insulin regulation, whereas insectivorous bats exhibited relatively higher levels of bile acid metabolites. Overall, this study provides theoretical insights into the metabolic adaptations of frugivorous bats and the glucose-response strategies of insectivorous bats, offering new perspectives on metabolite-based therapeutic approaches to diabetes.