Background: Aging is associated with a decline in cognitive function and vulnerability to depression. Probiotic supplements have shown beneficial effects on cognition and mood in clinical populations, but the potential benefit for healthy older adults experiencing age-related decline in cognition remains unclear.

Objectives: The primary aim of the present work was to explore the effect of a chronic (long-term) multispecies probiotic intervention on cognition in healthy aging adults. Secondary aims included exploring the chronic effect on mood outcomes and gut microbiota community, as well as a novel investigation into the acute effect of supplementation on cognition and mood.

Methods: The study employed a randomized, placebo-controlled, cross-over trial in 30 healthy older adults to explore the acute (1 d) and chronic (8 wk) effects of a probiotic supplement on cognitive domains of memory and executive function, alongside mood measures of stress, anxiety, depression, and cognitive reactivity to sad mood. 16s rRNA sequencing of stool samples was also performed pre- and postchronic intervention to assess potential effects on the gut microbiota.

Results: Acute probiotic supplementation was associated with faster reaction times on cognitively demanding trials during a task of executive function [-64.91 ms, 95% confidence interval (CI): -115.70, -14.15]. Chronic supplementation was associated with improvement in cognitive biases such as hopelessness (-0.97, 95% CI: -1.72, -0.23), rumination (-1.58, 95% CI: -2.86, -0.29), and aggression (-1.57, 95% CI: -2.63, -0.51) that contribute to reactivity to sad mood and therefore vulnerability to depression, and may improve executive function under higher cognitive demand (0.43%, 95% CI: -0.53%, 1.38%).

Conclusions: The current work provides novel evidence for an acute effect of probiotics on reaction times during executive function, which should be replicated in future work. Additionally, this work replicates previous findings of improved cognitive reactivity to sad mood following chronic probiotic supplementation, indicating probiotics may reduce risk of developing depression in a healthy aging population. This study was registered at clinicaltrials.gov as NCT04951687.