Porphyromonas gingivalis promotes the formation and development of type 2 diabetes mellitus complicated with cognitive impairment by regulating gut microbiota and metabolic pathways

Type 2 diabetes mellitus (T2DM) is associated with a series of chronic complications, of which cognitive impairment is a common complication of the central nervous system. Porphyromonas gingivalis (Pg), a gram-negative anaerobic bacillus with non-glycolytic sugar, is thought to be associated with the aggravation of diabetes, diabetes complications, and senile dementia. This study aimed to explore the role and mechanism of Pg in the development of cognitive impairment in T2DM. Cognitive ability, hippocampal neuron damage, synaptic plasticity, and microglial inflammation were analyzed in mice. Furthermore, the changes of microflora in the colon contents, and the content of short-chain fatty acids (SCFAs) in serum, and the expression of SCFA receptor Olfr78 in the hippocampus were analyzed. Pg promoted cognitive impairment, aggravated hippocampal neuron damage, reduced synaptic plasticity, and promoted microglial inflammatory response in T2DM mice. Gut microbiota sequencing and serum metabolomics results showed that Pg promoted gut microbiota disturbance in T2DM mice, affected the serum content of SCFAs, and reduced the expression of Olfr78 in the hippocampal tissue of T2DM mice. Pg may mediate the gut-brain axis through gut microbiota and its metabolic pathway, and participate in cognitive dysfunction of T2DM.