Live or heat-killed probiotic administration reduces anxiety and central cytokine expression in BALB/c mice, but differentially alters brain neurotransmitter gene expression

While the potential for probiotic supplements to act as adjunctive treatments for mood disorders has been widely demonstrated, the precise mode of action remains unclear. To investigate the psychotropic effects of a multi -species probiotic on emotional behaviour in male BALB/c mice, we explored the potential mechanisms of ac-tion relating to the temporal changes in the mRNA expression of brain cytokines, BDNF, central 5HT receptor and serotonin transporter (SERT) and GABA receptor in the context of probiotic induced behavioural changes. The effects of a heat-killed probiotic, independent of microbial metabolic processes were also evaluated on the same outcomes to understand whether the host response to the bacteria is more or less important than the contribution of the metabolic activity of the bacteria themselves. Results showed that probiotic supplementation reduced anxiety-like behaviours, increased time spent in the light area of the light-dark box, and decreased the expression of pro-inflammatory cytokines in the brain. Furthermore, probiotic administration elevated hippocampal BDNF and decreased GABAB1 beta expression. Interestingly, the heat-killed probiotic and its membrane fraction had similar effects on emotional behaviours and gene expression in the brain. The ingestion of live and heat-killed probiotic preparations also reduced TLR2 expression in the gut. Thus, the present study reveals that the anxiolytic action of a multispecies probiotic in BALB/c mice is independent of bacterial viability. This suggests that it is the host response to probiotics, rather than microbial metabolism that facilitates the molecular changes in the brain and downstream behaviours.This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".