The gut-brain axis and inflammatory mediators in suicide and mental disorders with high suicide rates: a review of current evidence

Abstract

The interplay between gastrointestinal microbiota and mental disorders has recently been spotlighted. This review investigated discrete evidence suggesting associations between the gastrointestinal microbiome and inflammation with suicide. Fusicatenibavter, Hungatella, Veillonella, and Megasphaera have positive associations, but Clostridium, Butyricicoccus, Desulfovibrio piger, and Parabacteroides merdae have negative associations with suicidality. Additionally, lower species uniformity index, higher intestinal fatty acid binding protein secretion, lower zonulin secretion, higher interleukin-6 in cerebrospinal fluid, and laxative abuse are associated with suicidality. As nearly 90% of suicides occur in patients with mental disorders, the interaction between the gut microbiota and inflammation with these disorders together was also documented. Regarding this, major depressive disorder, psychosis and schizophrenia, generalised anxiety disorder, and substance use disorder were investigated. Bacteroidetes and Firmicutes show prominent changes in most cases. In addition, gut bacterial and non-bacterial microbiome alterations and subsequent dysbiosis may contribute to inflammation, in which cytokines affect microglial activity. Meanwhile, impaired intestinal homeostasis may influence these disorders through the vagus nerve, the hypothalamus-pituitary-adrenal axis, and the kynurenine pathway. Beyond these, direct effects of the gut microbiome on immunity are being hypothesised. In conclusion, the gut microbiota imbalance may influence the nervous system environment from non-inflammatory to inflammatory caused by pro-inflammatory cytokine influx into the brain. Consequently, microbiota imbalances may be associated with mental disorders. Specifically, limited evidence indicated possible links between microbiome alterations and suicide, highlighting the need for further research clarifying these associations and underpinning mechanisms. Other factors, including genetic vulnerability, environmental influences, and neurochemical pathways, should also be considered.