Intestinal Dysbiosis, Gut Hyperpermeability and Bacterial Translocation: Missing Links Between Depression, Obesity and Type 2 Diabetes.
The comorbid prevalence of major depressive disorder (MDD) with obesity and type II diabetes mellitus reflects the existence of a subset of individuals with a complex common pathophysiology and overlapping risk factors. Such comorbid disease presentations imply a number of difficulties, including: decreased treatment responsivity and adherence; altered glycemic control and increased risk of wider medical complications. A number of factors link MDD to metabolic-associated disorders, including: higher rates of shared risk factors such as poor diet and physical inactivity and biological elements including increased inflammation; insulin resistance; oxidative and nitrosative stress; and mitochondrial dysfunction. All of these biological factors have been extensively investigated in the pathophysiology of obesity and type 2 diabetes mellitus as well as MDD. In this review, we aim to: (1) overview the epidemiological links between MDD, obesity and type 2 diabetes mellitus; (2) discuss the role of synergistic neurotoxic effects in MDD comorbid with obesity, and type 2 diabetes mellitus; (3) review evidence of intestinal dysbiosis, leaky gut and increased bacterial translocation, in the pathophysiology of MDD, obesity and type 2 diabetes mellitus; and (4) propose a model in which the gut-brain axis could play a pivotal role in the comorbidity of these disorders.
Anastasiya
A
Slyepchenko
Michael
M
Maes
Rodrigo
R
Machado-Vieira
George
G
Anderson
Marco
M
Solmi
Yolanda
Y
Sanz
Michael
M
Berk
Cristiano A
CA
Köhler
Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Rua Prof. Costa Mendes, 1608, 4º andar, 60430-040, Fortaleza, CE, Brazil.
André F
AF
Carvalho
D000818:Animals; D018988:Bacterial Translocation; D003866:Depressive Disorder / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D064806:Dysbiosis / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010539:Permeability