Prebiotic and Probiotic Modulation of the Microbiota-Gut-Brain Axis in Depression

Abstract

Emerging evidence demonstrates that alterations to the gut microbiota can affect mood, suggesting that the microbiota-gut-brain (MGB) axis contributes to the pathogenesis of depression. Many of these pathways overlap with the way in which the gut microbiota are thought to contribute to metabolic disease progression and obesity. In rodents, prebiotics and probiotics have been shown to modulate the composition and function of the gut microbiota. Together with germ-free rodent models, probiotics have provided compelling evidence for a causal relationship between microbes, microbial metabolites, and altered neurochemical signalling and inflammatory pathways in the brain. In humans, probiotic supplementation has demonstrated modest antidepressant effects in individuals with depressive symptoms, though more studies in clinically relevant populations are needed. This review critically discusses the role of the MGB axis in depression pathophysiology, integrating preclinical and clinical evidence, as well as the putative routes of communication between the microbiota-gut interface and the brain. A critical overview of the current approaches to investigating microbiome changes in depression is provided. To effectively translate preclinical breakthroughs in MGB axis research into novel therapies, rigorous placebo-controlled trials alongside a mechanistic and biochemical understanding of prebiotic and probiotic action are required from future research.

Keywords: depression; gut microbiota; metabolic disease; microbial metabolites; obesity.

Figure 1

Summary of the putative mechanisms of communication between the gut microbiota and the brain.

Figure 2

Summary of the evidence from human and/or rodent studies that demonstrate overlapping pathophysiology between obesity and major depressive disorder.

Figure 3

Potential mechanisms describing how diet-induced metabolic syndrome (obesity/NAFLD) may lead to altered brain plasticity and low mood. On the left side of the flowchart, chronic, low-grade inflammation is thought to upregulate peripheral indoleamine 2,3-dioxygenase (IDO1) activity, leading to increased kynurenine production from tryptophan and reduced brain tryptophan uptake for central serotonin synthesis. On the right, elevated circulating branched-chain amino acids may arise after prolonged high-fat diet feeding. BCAAs compete with tryptophan for the large neutral amino acid transporter (LAT1), reducing brain uptake of tryptophan and central serotonin synthesis. This may lead to altered neurotransmission and low mood. ↑ increase.