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Stress negatively affects cognitive performance. Probiotics remediate somatic and behavioral stress responses, hypothetically by acting on the gut microbiota. Here, we assessed gut microbial alterations after 28-days supplementation of multi-strain probiotics (EcologicBarrier consisting of Lactobacilli, Lactococci and Bifidobacteria in healthy, female subjects (probiotics group n=27, placebo group n=29). In an identical pre- and post-session, subjects performed a working memory task before and after an acute stress intervention. One-month supplementation of probiotics changed the gut microbial community (within probiotics group Pweighted unifrac=0.008). This change was driven by a nominal increase in eight genera in the probiotics group relative to the placebo group: Butyricimonas, Parabacteroides, Alistipes, Christensenellaceae_R-7_group, Family_XIII_AD3011_group, Ruminococcaceae_UCG-003, Ruminococcaceae_UCG-005 and Ruminococcaceae_UCG-010. Of these, the probiotics-induced change in genus Ruminococcaceae_UCG-003 was significantly associated with probiotics’ effect on stress-induced working memory changes (rspearman(27) = 0.565; pFDR = 0.014) in the probiotics group only and independent of potential confounders (i.e., age, BMI, and baseline dietary fibre intake). That is, subjects with a higher increase in Ruminococcaceae_UCG-003 abundance after probiotics were also more protected from negative effects of stress on working memory after probiotic supplementation. The bacterial taxa showing an increase in relative abundance in the probiotics group are plant fibre degrading bacteria and produce short-chain fatty acids that are known for their beneficial effect on gut and brain health, e.g. maintaining intestinal- and blood-brain-barrier integrity. This study shows that gut microbial alterations, modulated through probiotics use, are related to improved cognitive performance in acute stress circumstances.

Probiotics are microorganisms that provide health benefits when consumed. In animals, probiotics reverse gut microbiome-related alterations in depression-like symptoms, in cognition, and in hormonal stress response. However, in humans, a causal understanding of the gut-brain link in emotion and cognition is lacking. Additionally, whether the effects of probiotics on neurocognition are visible only in presence of stress, remains unclear. We investigated the effects of a multispecies probiotic (Ecologic®Barrier) on specific neurocognitive measures of emotion reactivity, emotion regulation, and cognitive control using fMRI. Critically, we also tested whether probiotics can buffer against the detrimental effects of acute stress on working memory. In a double blind, randomized, placebo-controlled, between-subjects intervention study, 58 healthy participants were tested once before and once after a 28-day intervention. Without stress induction, probiotics did not affect brain, behavioral, or related self-report measures. However, relative to placebo, the probiotics group did show a significant stress-related increase in working memory performance after supplementation. This change was associated with intervention-related neural changes in frontal cortex during cognitive control exclusively in the probiotics group. Overall, our results show neurocognitive effects of a multispecies probiotic in healthy women only under challenging situations, buffering against the detrimental effects of stress on cognition., Highlights • We ran a randomized placebo-controlled fMRI study with a multispecies probiotic. • Probiotics did not affect neurocognitive measures of emotion and cognitive control. • Probiotics did affect stress-related working memory and neural correlates. • Probiotics in healthy individuals can support cognition under stress.

Probiotics are microorganisms that can provide health benefits when consumed. Recent animal studies have demonstrated that probiotics can reverse gut microbiome-related alterations in anxiety and depression-like symptoms, in hormonal responses to stress, and in cognition. However, in humans, the effects of probiotics on neurocognition remain poorly understood and a causal understanding of the gut-brain link in emotion and cognition is lacking. We aimed to fill this gap by studying the effects of a probiotics intervention versus placebo on neurocognition in healthy human volunteers.We set out to investigate the effects of a multispecies probiotic (Ecologic®Barrier) on specific neurocognitive measures of emotion reactivity, emotion regulation, and cognitive control using fMRI. Critically, we also tested whether the use of probiotics can buffer against the detrimental effects of acute stress on working memory. In a double blind, randomized, placebo-controlled, between-subjects intervention study, 58 healthy participants were tested twice, once before and once after 28 days of intervention with probiotics or placebo.Probiotics versus placebo did not affect emotion reactivity, emotion regulation, and cognitive control processes at brain or behavioral level, neither related self-report measures. However, relative to the placebo group, the probiotics group did show a significant stress-related increase in working memory performance after versus before supplementation (digit span backward, p=0.039, ηp2=.07). Interestingly, this change was associated with intervention-related neural changes in frontal cortex during cognitive control in the probiotics group, but not in the placebo group. Overall, our results show that neurocognitive effects of supplementation with a multispecies probiotic in healthy women become visible under challenging (stress) situations. Probiotics buffered against the detrimental effects of stress in terms of cognition, especially in those individuals with probiotics-induced changes in frontal brain regions during cognitive control.HighlightsWe ran a randomized placebo-controlled fMRI study with a multispecies probioticProbiotics did not affect neurocognitive measures of emotion and cognitive controlProbiotics did affect stress-related working memory and neural correlatesProbiotics in healthy individuals can support cognition under stress