Functional associations of the gut microbiome with dopamine, serotonin, and BDNF in schizophrenia: a pilot study

Background Schizophrenia is a complex neuropsychiatric disorder with various etiologic factors. Aberrant levels of neurotransmitters or growth factors such as dopamine, serotonin, and BDNF have been shown to cause cognitive impairment in schizophrenia. Recently, the gut microbiome has also been suggested as a factor in the development of the disorder. To explore this potential link, we conducted a pilot study to examine the relationship between the gut microbiome and plasma levels of neurotransmitters and growth factors in schizophrenia. Shotgun metagenome sequencing of total RNA from fecal samples were used to profile the gut microbiome of schizophrenia patients (SCZ) and healthy controls (HC). The MetaPhlAn2 and HUMaN2 pipelines were used for bioinformatic analyses. ELISA was used to measure the plasma levels of dopamine, serotonin, and BDNF. Spearman’s rank correlation coefficient was used for correlation analysis. Results We found that butyrate-producing bacteria were enriched in HC, whereas succinate-producing bacteria, namely Phascolarctobacterium succinatutens and Paraprevotella clara , were enriched in SCZ. The gut microbiota of SCZ was enriched in lipid biosynthesis pathways related to bile-resistant bacteria, whereas phospholipid pathways linked with butyrate-producing bacteria were enriched in HC. Alistipes indistinctus , Dorea longicatena , and Roseburia inulinivorans were negatively correlated with dopamine levels. Roseburia intestinalis and Parabacteroides goldsteini were negatively correlated with serotonin and BDNF levels, respectively. We found a significant correlation between dopamine and serotonin levels, and the super-pathway of purine deoxyribonucleoside degradation. Conclusions This study provides further support that gut microbiota could modulate neurotransmitter levels. The results suggest that gut microbiome-targeted therapies may help to rebalance neurotransmitter levels, offering new hope for the treatment of schizophrenia.