Linking Obesity and Depression Through the Gut–Brain Axis: The Impact of Short-Chain Fatty Acids and Inflammation

Abstract

Obesity is a major public health problem that puts pressure on healthcare systems globally. The purpose of this narrative review is to summarize and analyse recent research on the bidirectional link between obesity and mental health, focusing on the biological, behavioural, dietary, emotional, and metabolic mechanisms arising from gut microbiota interactions. Epidemiological association between obesity and mental health disorders, especially depression and anxiety, often occurs bidirectionally, reinforcing each other. Low-grade systemic inflammation is a condition typically found in obesity, being a fundamental element of neuropsychiatric disorders. Considered the main energy substrate for colon cells, SCFAs are synthesized in the intestine and exert important local effects by reducing both local and systemic inflammation. The intestinal microbiota maintains this homeostasis through the SCFAs it produces. The combined impact of the increased intestinal permeability, immune activation, and disrupted metabolism of SCFAs and tryptophan contributes to the onset and progression of depression and anxiety, as well as to significant cognitive dysfunction, especially in obese individuals. Understanding the mechanisms by which microbiota metabolites influence brain development, neuroplasticity, and behaviour could pave the way for new and innovative therapeutic strategies for the treatment of obesity and depression. Conclusions: The association of these pathologies is not coincidental, as they coexist through overlapping biological pathways that they partially or completely share. The main pathway involved is formed by the brain–gut axis and its mediators (SCFAs).