Type 1 diabetes induces cognitive dysfunction in rats associated with alterations of the gut microbiome and metabolomes in serum and hippocampus

Cognitive decline is a common symptom at advanced stage of type 1 diabetes (T1D), but its potential pathogenesis remains unclear. In this study, therefore, we investigated changes in the gut microbiome and metabolome in serum and hippocampus between advanced-stage T1D (AST1D) rats with cognitive decline and age matched controls (AMC), and explored the possible mechanism of the gut-microbiota-metabolite axis in T1D-induced cognitive dysfunction. The results demonstrated that AST1D rats possessed peculiar metabolic phenotypes in serum and hippocampus relative to AMC rats, as characterized by decreases in tricarboxylic acid (TCA) cycle and amino acid and choline metabolism as well as disturbances in glutamate/GABA-glutamine cycle and astrocyte-neuron metabolism. We also found that AST1D rats had higher relative abundances of Prevotella_9, Bacteroides and Lachnospiraceae_NK4A136_group as well as lower relative abundances of Clostridium sensu stricto 1, Romboutsia and Turicibacter than AMC rats. Microbiota-host metabolic correlation analysis suggests that metabolic alterations in serum and hippocampus may be modulated by the gut microbiota, especially Clostridium sensu strict 1, Romboutsia and Turicibacter. Therefore, our study implies that the modification of host metabolism by targeting the gut microbiota may be a novel avenue for prevention and treatment of diabetic encephalopathy in the future.