The Effects of a Probiotic on Emotional and Cognitive Processing in Participants Experiencing Low Mood

Current antidepressant treatments, which largely target monoamine pathways, are efficacious in treating many aspects of major depression, however it is estimated that more than 30% of depressed patients fail to respond to standard antidepressant medications. Thus, there is a strong clinical need to identify and investigate novel treatment strategies that target different pathways involved in the pathophysiology of mood disorders.

There is now compelling evidence for a link between the enteric microbiota and brain function. The proliferation of the Bifidobacteria and Lactobacilli strains in the large intestine, have anxiolytic and mnemonic effects in both rodents and humans. The intake of these bacteria as live cultures (probiotics) alters the expression of genes integral to neurodevelopment and complex behaviours in rodents. For instance, the oral administration of Bifidobacteria to rats elevated hippocampal brain-derived neurotrophic factor (BDNF), which may underlie some antidepressant actions . At present, only several probiotics have been examined, but it seems likely that of the 40,000 species in the gut, there will be others with psychotropic properties. A multispecies probiotic (Bio-Kult) that contains several species of Bifidobacteria and Lactobacilli is now available and of the 14 types of bacteria packaged into a capsule, 50% have been shown to have psychotropic effects in animals. Dietary supplementation with Bio-Kult therefore, presents as an optimal strategy to test the influence of beneficial gut bacteria on emotional processing and cognition because, the numerous types of bacteria ingested may have a synergistic effect on the brain and so convey a 'stronger' action compared to single species probiotics.

The translation from rodent to human investigations of probiotics has been surprisingly robust, though many more human studies are necessary. In an important early investigation male and female participants consumed either a fermented milk drink containing Lactobacillus casei Shirota or a placebo. At the end of the three-week intervention, there were no overall changes in self-reported affect. However, when only participants whose baseline mood scores fell in the lowest third of the total range were analysed, probiotic supplementation resulted in significantly more participants self-rating as happy rather than depressed, relative to placebo. These results suggest that the emotional benefits of probiotics may be subject to ceiling effects.

Similar effects have been observed in other investigations of mood. For instance, in a recent randomised controlled trial, healthy participants consumed a placebo product or a mixture of several probiotics (Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis W19 and W58) over a period of four weeks. Relative to placebo, probiotic-treated participants exhibited substantially reduced reactivity to sad mood (assessed by the Leiden Index of Depression Sensitivity Scale), an effect that was specifically attributable to fewer instances of rumination and aggressive cognitions.

In a randomized and double-blind design, healthy volunteers consumed either a mixture of probiotics (Lactobacillus helveticus R0052 and Bifidobacterium longum) or a placebo over 30 days, after which participants completed a range of self-report measures on mood and distress. Participants also collected urine over 24 hours before and after the intervention, enabling cortisol estimations. Relative to placebo, probiotic-treated participants showed significant declines in self-reported negative mood and distress. Parallel to these changes was a decrease in urinary free cortisol, which is suggestive of a potential mechanism underlying the self-reported affective improvements. Interestingly, a follow-up analysis of the individuals with the lowest stress (indexed by cortisol concentrations) showed similar affective benefits to those with higher cortisol concentrations, to some extent contravening the role of ceiling effects in determining probiotic outcomes.