The Role of the Adrenal-Gut-Brain Axis on Comorbid Depressive Disorder Development in Diabetes

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2023-10, Vol.13 (10), p.1504
• Main Authors: Mázala-de-Oliveira, Thalita, Silva, Bruna Teixeira, Campello-Costa, Paula, Carvalho, Vinicius Frias
• Format: Article
• Language: English
• Subjects: Adrenal glands; Animals; Apoptosis; Bacteria; Blood-brain barrier; Brain-Gut Axis; Care and treatment; Chronic illnesses; Comorbidity; Complications and side effects; Cushing Syndrome; depression; Depression, Mental; Depressive Disorder; Development and progression; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental; Diabetics; Digestive system; Disease; Dysbacteriosis; Dysbiosis; Emotional disorders; Enzymes; Expenditures; Feedback; Gastrointestinal tract; glucocorticoids; Glutamatergic transmission; gut microbiota; Hippocampus; Homeostasis; Hormones; Humans; Hyperactivity; Hyperglycemia; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - physiology; Hypothalamus; Inflammation; Lipopolysaccharides; Membrane permeability; Mental depression; Metabolism; Metabolites; Mice; Microbiota; Mood disorders; Neuroinflammatory Diseases; Permeability; Pituitary gland; Pituitary-Adrenal System - physiology; Probiotics; Proteins; Psychological aspects; Review; Risk factors; TLR4; TLR4 protein; Toll-like receptors; Treatment resistance; treatment-resistant depression
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom13101504

Diabetic patients are more affected by depression than non-diabetics, and this is related to greater treatment resistance and associated with poorer outcomes. This increase in the prevalence of depression in diabetics is also related to hyperglycemia and hypercortisolism. In diabetics, the hyperactivity of the HPA axis occurs in parallel to gut dysbiosis, weakness of the intestinal permeability barrier, and high bacterial-product translocation into the bloodstream. Diabetes also induces an increase in the permeability of the blood-brain barrier (BBB) and Toll-like receptor 4 (TLR4) expression in the hippocampus. Furthermore, lipopolysaccharide (LPS)-induced depression behaviors and neuroinflammation are exacerbated in diabetic mice. In this context, we propose here that hypercortisolism, in association with gut dysbiosis, leads to an exacerbation of hippocampal neuroinflammation, glutamatergic transmission, and neuronal apoptosis, leading to the development and aggravation of depression and to resistance to treatment of this mood disorder in diabetic patients.