How Microbes Affect Depression: Underlying Mechanisms via the Gut–Brain Axis and the Modulating Role of Probiotics

Abstract

Accumulating evidence suggests that the gut microbiome influences the brain functions and psychological state of its host via the gut–brain axis, and gut dysbiosis has been linked to several mental illnesses, including major depressive disorder (MDD). Animal experiments have shown that a depletion of the gut microbiota leads to behavioral changes, and is associated with pathological changes, including abnormal stress response and impaired adult neurogenesis. Short-chain fatty acids such as butyrate are known to contribute to the up-regulation of brain-derived neurotrophic factor (BDNF), and gut dysbiosis causes decreased levels of BDNF, which could affect neuronal development and synaptic plasticity. Increased gut permeability causes an influx of gut microbial components such as lipopolysaccharides, and the resultant systemic inflammation may lead to neuroinflammation in the central nervous system. In light of the fact that gut microbial factors contribute to the initiation and exacerbation of depressive symptoms, this review summarizes the current understanding of the molecular mechanisms involved in MDD onset, and discusses the therapeutic potential of probiotics, including butyrate-producing bacteria, which can mediate the microbiota–gut–brain axis.

The effect of pro-/synbiotic supplementation on the brain-derived neurotrophic factor: a systematic review and meta-analysis of randomized controlled trials

“…Butyrate can enter the systemic circulation and cross the blood-brain barrier into the brain. 35 Afterwards, butyrate can result in acetylation of…”

The molecular pathophysiology of depression and the new therapeutics

“…Several studies have revealed that the microbiota-gutbrain axis is important for regulating mood, behavior, and neuronal transmission in the brain, 113,114 and is associated with MDD. [115][116][117] Several studies have suggested that depression and gastrointestinal disorders are comorbid. 118,119 Some antidepressants can alleviate the symptoms of people suffering from irritable bowel syndrome and other related disorders.…”

“…133,134 Furthermore, short-chain fatty acids, such as butyrate, are known to increase BDNF levels, whereas gut dysbiosis decreases BDNF levels; which could have an impact on neuronal development and synaptic plasticity. 115 There has been significant progress in research in this area, but more clinical trials are required to determine whether probiotics are effective in treating depression. In addition, the underlying mechanisms need to be elucidated.…”

“…Recent attention has been drawn to the microbiota–gut–brain axis owing to its potential to regulate brain activity. Several studies have revealed that the microbiota–gut–brain axis is important for regulating mood, behavior, and neuronal transmission in the brain, 113,114 and is associated with MDD 115–117 . Several studies have suggested that depression and gastrointestinal disorders are comorbid 118,119 .…”

“…Additionally, recent studies have indicated that changes in the gut microbiota can damage the gut barrier and increase peripheral inflammatory cytokines 133,134 . Furthermore, short‐chain fatty acids, such as butyrate, are known to increase BDNF levels, whereas gut dysbiosis decreases BDNF levels; which could have an impact on neuronal development and synaptic plasticity 115 . There has been significant progress in research in this area, but more clinical trials are required to determine whether probiotics are effective in treating depression.…”