Kynurenine Pathway and Gut Microbiota: Treatment Applications for Schizophrenia Ali Abdolizadeh
Previous studies reported increased pro-inflammatory markers in schizophrenia (SCZ) patients (MĂźller 2018). In addition, altered tryptophan (Trp) metabolism and dysregulation of its metabolites have been observed in inflammation-associated diseases (Dantzer 2017). The gut microbiota modulates different pathways of Trp metabolism and influences brain function (Gao et al. 2020). Significant contributions of dysregulated gut microbiota to neuropsychiatric disorders through the gut-brain axis have been highlighted in the past decade (Petra et al. 2015). However, it is still unclear whether microbiota alteration itself leads to neuropsychiatric diseases, or in turn, microbiota dysbiosis is a result of mental disorders. The original paper sought to further investigate the causation of this process (Zhu et al. 2019). They performed fecal microbiota transplantation (FMT) from antipsychotic-free individuals with schizophrenia (SZC) and healthy controls (CS) into specific pathogen-free (SPF) mice. Following FMT, behavioural tests revealed impaired spatial learning and memory, increased exploratory activity, and enhanced rearing behaviour in SPF mice treated with fecal-derived microbiota from SCZ individuals. Moreover, kynurenine (Kyn) and kynurenic acid (Kyna) levels of Trp metabolites were elevated in both peripheral tissues and the central nervous system of SCZ mice. Nonetheless, the exact mechanism by which the gut microbiota contributes to schizophrenia pathogenesis remains unclear. The current paper aims to review the role of the gut microbiota in brain functions, focusing on the Trp metabolism and Kyn pathway. This review further elucidates the link between Kyn metabolites and schizophrenia for potential therapeutic targets. Key words: schizophrenia (SZC), tryptophan (Trp) metabolism, microbiota, brain-gut axis, impaired learning and memory, kynurenine (Kyn), Kynurenic acid (Kyna), fecal microbiota transplantation (FMT).
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