Identifying and ranking causal association between gut microbiota and neuroticism.

BACKGROUNDRecent studies had explored that gut microbiota was associated with personality traits through the gut-brain axis. Nevertheless, the fundamental causality remained obscure.

METHODSMendelian randomization (MR) was used to investigate the causal relationship between gut microbiota, metabolites and neuroticism-related traits. Summary data-based Mendelian randomization (SMR) was utilized to identify genes associated pleiotropically with microbial taxa.

RESULTSMR analyses identified reliable causal evidence of 20 bacterial taxa related to neuroticism and its worry or depressed affect sub-cluster. A higher relative abundance of the Ruminococcus gauvreauii genus was associated with a higher risk of neuroticism [odds ratio (OR) = 1.04, 95% CI: 1.02-1.06, P = 2.85 × 10-3], depressed affect [OR = 1.04, 95% CI: 1.02-1.06, P = 5.50 × 10-3] and worry (OR = 1.04, 95% CI: 1.02-1.06, P = 7.81 × 10-4), respectively. We identified the probes tagging CPSF1, that showed pleiotropic association with Ruminococcus gauvreauii in brain or colon tissues. Finally, we provided evidence that Ruminococcus gauvreauii present causal association with the neurotransmitter such as glutamine and glutamate.

CONCLUSIONSThis study implied a causal relationship between the gut microbiome composition, metabolites and neuroticism, thus providing novel insights into the gut microbiota-mediated development mechanism of neuroticism.