The Microbiota–Gut–Brain Axis and Diabetic Cognitive Impairment: A Memorable Journey

Objective: Diabetes mellitus (DM) is associated with complications affecting the quality of life. Interest-ingly, the gut microbiota is closely related to glucose metabolism. This narrative review introduces the characteristics of the gut microbiota in DM, describes the modulation of host glycemic control by the gut microbiota, characteristics of intestinal permeability, mechanisms of diabetic cognitive impairment (DCI), and the role of brain–gut–microbiota axis in DM. Materials and methods: The literature search was performed in Medline, Scopus, WOS, and PubMed databases using the keywords gut microbiota, DM, intestinal permeability, and DCI. Results: Dysbiosis of gut microbiota causes intestinal barrier disruption resulting in the entry of intestinal bacteria and their metabolites into the circulatory system, which may disturb insulin sensitivity, glucose metabolism, and immune homeostasis. Gut microbiota plays a critical role in regulating systemic insulin sensitivity and energy metabolism. Intestinal barrier dysfunction induced by hyperglycemia is considered to be the underlying mechanism of systemic infection and inflammatory response in patients with diabetes. Both dysbacteriosis and cytokines will lead to the intestinal barrier and blood–brain barrier dysfunction, facilitating harmful substances (advanced glycated end products) to access neurons, and thus contribute to the development of DCI. The modulation of intestinal permeability through nutritional interventions may represent a potential prevention target for DM. Conclusions: The clinical evidence for the association between hyperglycemia and intestinal barrier dysfunction in humans is scarce. Further clinical studies are needed to provide more insight by studying the intestinal barrier integrity markers and glycemic status and their association with cognitive status. (Clin Diabetol 2023; 12; 4: 261–271)