Objectives:This trial investigated whether probiotics improved mood, stress and anxiety in a sample selected for low mood. We also tested whether the presence or severity of irritable bowel syndrome symptoms, and levels of proinflammatory cytokines, brain-derived neurotrophic factor and other blood markers, would predict or impact treatment response.Method:Seventy-nine participants (10 dropouts) not currently taking psychotropic medications with at least moderate scores on self-report mood measures were randomly allocated to receive either a probiotic preparation (containing Lactobacillus helveticus and Bifidobacterium longum) or a matched placebo, in a double-blind trial for 8 weeks. Data were analysed as intent-to-treat.Results:No significant difference was found between the probiotic and placebo groups on any psychological outcome measure (Cohen’s d range = 0.07–0.16) or any blood-based biomarker. At end-point, 9 (23%) of those in the probiotic group showed a ⩾60% change on the Montgomery–Åsberg Depression Rating Scale (responders), compared to 10 (26%) of those in the placebo group (χ12=0.107, p = ns). Baseline vitamin D level was found to moderate treatment effect on several outcome measures. Dry mouth and sleep disruption were reported more frequently in the placebo group.Conclusions:This study found no evidence that the probiotic formulation is effective in treating low mood, or in moderating the levels of inflammatory and other biomarkers. The lack of observed effect on mood symptoms may be due to the severity, chronicity or treatment resistance of the sample; recruiting an antidepressant-naive sample experiencing mild, acute symptoms of low mood, may well yield a different result. Future studies taking a preventative approach or using probiotics as an adjuvant treatment may also be more effective. Vitamin D levels should be monitored in future studies in the area. The results of this trial are preliminary; future studies in the area should not be discouraged.

More trials are necessary before any inferences can be made about the efficacy of probiotics in mental health applications.

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We live in a transformational moment for understanding the etiology of mental disorders. The previous leap in understanding occurred 60 years ago, which led us to incorporate psychopharmacology into our curricula to address the chemical basis of neurotransmitter function, especially as explained through the then-popular catecholamine hypothesis. The current revolution is broader, consisting of the rapidly accumulating knowledge of how inflammation, microbiome imbalance (gut dysbiosis), oxidative stress, and impaired mitochondrial output affect brain function. Suitable interventions for fighting inflammation, restoring normal gut function, reducing oxidative stress, and improving mitochondrial metabolism incorporate lifestyle variables, including nutrients and probiotics. This article invites readers to stay abreast of this emerging model of the biological basis of mental illness, given that it has particular relevance for those readers interested in alleviating the suffering of individuals with mental disorders. This overview describes the basis for a new field in mental health: nutritional psychiatry/psychology.