Interplay Between the Gut-Brain Axis, Obesity and Cognitive Function

Abstract

Obesity continues to be one of the major public health problems due to its high prevalence and co-morbidities. Common co-morbidities not only include cardiometabolic disorders but also mood and cognitive disorders. Obese subjects often show deficits in memory, learning and executive functions compared to normal weight subjects. Epidemiological studies also indicate that obesity is associated with a higher risk of developing depression and anxiety, and vice versa. These associations between pathologies that presumably have different etiologies suggest shared pathological mechanisms. Gut microbiota is a mediating factor between the environmental pressures (e.g., diet, lifestyle) and host physiology, and its alteration could partly explain the cross-link between those pathologies. Westernized dietary patterns are known to be a major cause of the obesity epidemic, which also promotes a dysbiotic drift in the gut microbiota; this, in turn, seems to contribute to obesity-related complications. Experimental studies in animal models and, to a lesser extent, in humans suggest that the obesity-associated microbiota may contribute to the endocrine, neurochemical and inflammatory alterations underlying obesity and its comorbidities. These include dysregulation of the HPA-axis with overproduction of glucocorticoids, alterations in levels of neuroactive metabolites (e.g., neurotransmitters, short-chain fatty acids) and activation of a pro-inflammatory milieu that can cause neuro-inflammation. This review updates current knowledge about the role and mode of action of the gut microbiota in the cross-link between energy metabolism, mood and cognitive function.

Keywords: behavior; cognition; microbiota; mood; obesity.

Figure 1

Interplay between the microbiota and the gut-brain axis in obesity and associated mental disorders. Gut microbiota contributes to regulating the gut-brain axis and maintaining health, while its alteration (dysbiosis) due to lifestyle factors (unhealthy diets, stress) is related to obesity and its adverse consequences on mood and cognition. A healthy dietary pattern (e.g., rich in fibers, vegetables, etc.) is thought to increase gut microbiota diversity and, thereby, contribute to epithelial gut integrity, immune homeostasis and normal CNS function through the gut-brain axis. On the contrary, Western-dietary patterns (rich in simple sugars and saturated fat) seem to reduce microbial diversity, promote inflammation and contribute to the leaky gut syndrome; this facilitates the translocation of components of Gram-negative bacteria, which increases the peripheral inflammatory tone and produces neuroinflammation and alterations in the CNS. The use of dietary strategies (e.g., probiotics, healthier diets rich in fiber, prebiotics, etc.) could beneficially impact on obesity and mental complications, via restoration of a healthy microbiota and its regulatory role in the gut-brain axis.

Figure 2

Mood and cognitive alterations in obesity: the role of the gut-brain axis. The diversity and stability of the gut microbiota can be affected by high-fat diets (HFD) or high carb diets leading to dysbiosis, which is a typical alteration observed in obesity. A dysbiotic microbiota is thought to alter the communication between the gut and the brain axis contributing to mood alterations like anxiety, depression, sensitivity to stress, social behavioral alterations and cognitive alterations like hippocampal dysfunction, impaired memory and reduction of attention or the executive function. The use of some probiotics has demonstrated to ameliorate some of the mood alterations like anxiety or depression through different mechanisms in animal models.