Role of Brain-Gut-Microbiota Axis in Depression: Emerging Therapeutic Avenues

Abstract

The human gut microbiota plays a significant role in the pathophysiology of central nervous system related diseases. Recent studies suggest correlations between the altered gut microbiota and major depressive disorder (MDD). It is proposed that normalization of the gut microbiota alleviates MDD. The imbalance of brain-gut-microbiota axis also results in dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. This imbalance has a crucial role in the pathogenesis of depression. Treatment strategies with certain antibiotics lead to the depletion of useful microbes and thereby induce depression like effects in subjects. Microbiota is also involved in the synthesis of various neurotransmitters (NTs) like 5-hydroxy tryptamine (5-HT; serotonin), norepinephrine (NE) and dopamine (DA). In addition to NTs, the gut microbiota also has influence on brain derived neurotrophic factor (BDNF) levels. Recent research findings have exhibited that transfer of stress prone microbiota in mice is also responsible for depression and anxiety-like behaviour in animals. The use of probiotics, prebiotics, synbiotics and proper diet have shown the beneficial effects in the regulation of depression pathogenesis. Moreover, transplantation of fecal microbiota from depressed individuals to the normal subjects also induces depression like symptoms. With the precedence of limited therapeutic benefits from monoamine targeting drugs, the regulation of brain-gut microbiota is emerging as a new treatment modality for MDDs. In this review, we elaborate the significance of brain-gut-microbiota axis in the progression of MDD, particularly focusing on the modulation of the gut microbiota as a mode of treating MDD.

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.…”

“…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 .…”

Biology of cyclooxygenase-2: An application in depression therapeutics

“…development, function, mood and cognition may be influenced by the symbiotic flora (30). The gut microbiota and CNS are connected through multiple bidirectional pathways involving neural, endocrine, and immune signaling, and dysbiosis of the gut flora can cause psychiatric disorders, such as depression (31)(32)(33). Current studies suggest that intestinal flora dysbiosis can mediate depression by causing an inflammatory response (34,35).…”

Big data analytics frameworks for the influence of gut microbiota on the development of tic disorder

“…The association between gut microbiota and psychiatric disorders has received increasing research attention ( Morais et al, 2021 ). Over the past decade, many studies have revealed that the gut microbiota is directly involved in the production of various neurotransmitters, such as gamma-aminobutyric acid (GABA), serotonin (5-HT), glutamate, and dopamine (DA) ( Bull-Larsen and Mohajeri, 2019 ; Altaib et al, 2021 ; Bhatt et al, 2022 ), which are closely associated with a number of psychiatric disorders, including TD ( Kanaan et al, 2017 ), ADHD ( Turna et al, 2020 ), OCD ( Simpson et al, 2021 ), and anxiety ( Ridaura and Belkaid, 2015 ).…”

“…The association between gut microbiota and psychiatric disorders has received increasing research attention (Morais et al, 2021). Over the past decade, many studies have revealed that the gut microbiota is directly involved in the production of various neurotransmitters, such as gamma-aminobutyric acid (GABA), serotonin (5-HT), glutamate, and dopamine (DA) (Bull-Larsen and Mohajeri, 2019;Altaib et al, 2021;Bhatt et al, 2022), which are closely associated with a number Abbreviations: TD, Tic disorder; DSM, Diagnostic and Statistical Manual of Mental Disorders; TS, Tourette syndrome; CTD, chronic motor or vocal tic disorder; PTD, provisional tic disorder; OCD, obsessive-compulsive disorder; ADHD, attention-deficit/hyperactivity disorder; GABA, gammaaminobutyric acid; 5-HT, serotonin; DA, glutamate and dopamine; FMT, fecal microbiota transplantation; HC, healthy control; NOS, Newcastle-Ottawa Scale; GSI, gastrointestinal severity index; DRA, dopamine receptor antagonists; YGTSS, Yale Global Tic Severity Scale; ASD, autism spectrum disorders; SCFA, short-chain fatty acid.…”