Comorbid brain disorders associated with diabetes: therapeutic potentials of prebiotics, probiotics and herbal drugs

Prevalence of diabetes and comorbid brain disorders is increasing worldwide particularly in low- and middle-income countries. Diabetes and its complications impose substantial economic costs on the developing countries. Several comorbid conditions have been described for diabetes including central nervous system (CNS) disorders. Molecular changes in CNS due to chronic hyperglycemia could be the root cause of psychiatric comorbidities in metabolic syndrome as dietary carbohydrates and proteins affect plasma concentrations of many neurotransmitters involved in brain function. Glucose metabolism play an important role related in neuroenergetics, neurotransmission, energy storage, biosynthesis and oxidative defense. Thus, tight regulation of glucose metabolism is critical for normal brain physiology. An exaggerated symptom of depression, anxiety, and cognitive deficits are shown in diabetic animal models as well as in a population-based studies. Several studies show that many of the CNS acting drugs affected the glucose homeostasis and modulate brain physiology apart from their primary pharmacological actions. Gut-microbiota involve in the modulation of various physiological and pathological conditions of metabolic disorders and mental health by influencing the regulation of energy balance and release of neurotransmitters. Presently, no specific pharmacotherapies are available for CNS comorbidities associated with diabetes. However, some prebiotics, probiotics and herbal drugs are playing promising role in management of these CNS complications. Therefore, the evidence-based studies through translational research and clinical setup are warranted for better understanding for the relationship between brain glucose homeostasis and CNS complication as well as development of poly-pharmacologically active therapeutic drugs for the management of comorbid disorders associated with diabetic patients.