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.

The atypical antipsychotic lurasidone positively modulates the gut microbiota in rats: A comparative study to olanzapine

“…C. C. Kao et al, 2016; A. C.-C. Kao, Burnet, et al, 2018; Radford-Smith & Anthony, 2023). Following this, the present investigation lays the groundwork for clinical trials to determine whether the findings observed in rodents correlate with the effects of lurasidone on the human gut microbiome.…”

Advances in Brain–Gut–Microbiome Interactions: A Comprehensive Update on Signaling Mechanisms, Disorders, and Therapeutic Implications

“…Recent research has explored the effects of various prebiotic fibers, such as inulin, fructooligosaccharides, and galactooligosaccharides, on the BGM system. 119 , 120 Several studies have shown that prebiotic supplementation can modulate the gut microbial composition positively, increase the production of SCFAs, and improve gut barrier function. 121 These effects have been associated with improved cognitive function, reduced anxiety-like behavior, and enhanced stress resilience in animal models, but clinically meaningful effects need to be confirmed in well-controlled human studies.…”

Gastrointestinal barrier function, immunity, and neurocognition: The role of human milk oligosaccharide (hMO) supplementation in infant formula

“…For example, bacterial fermentation products such as SCFAs have been linked to the pathogenesis of depression (Radford‐Smith & Anthony, 2023). However, there is an overlap between the proposed pathways of cognitive disfunction caused by bacteria and the way in which the gut microbiota is considered to contribute to metabolic disease progression and obesity (Radford‐Smith & Anthony, 2023). Additionally, cognitive impairment has been previously linked to inflammation as well as to barrier disruption in both the gut and brain (Leigh & Morris, 2020).…”

“…The bacterial composition of the GI tract has been linked to changes in the brain and behavior, particularly with respect to cognitive function (Gareau, 2016). For example, bacterial fermentation products such as SCFAs have been linked to the pathogenesis of depression (Radford‐Smith & Anthony, 2023). However, there is an overlap between the proposed pathways of cognitive disfunction caused by bacteria and the way in which the gut microbiota is considered to contribute to metabolic disease progression and obesity (Radford‐Smith & Anthony, 2023).…”