ABSTRACT Background Emerging evidence indicates that gut microbiota-targeted interventions may lead to improvements in cognition. We assessed whether a prebiotic-rich dietary intervention, probiotic supplement, or synbiotic combination of both would improve human cognition, as part of the ‘Gut Feelings’ trial. Methods An 8-week, 2 × 2 factorial randomised controlled trial was conducted on 118 adults with low mood and potential for dietary improvement. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). At baseline and 8-weeks, the Cogstate Brief Battery was administered, testing processing speed, attention, visual learning, and working memory. Data were analysed using Bayesian linear regression. Results We found weak evidence that the probiotic improved working memory (Cohen’s d = −0.32, 95% CI: –0.67, 0.03; posterior probability [post. prob] of benefit: 96%). For the other treatments, there was little or no evidence of cognitive improvement. We found weak evidence that the prebiotic diet impaired processing speed (d = 0.25, 95% CI: –0.02, 0.51; post. prob of harm: 97%). There was little indication of a synergistic interaction between the probiotic and prebiotic diet. Conclusion We found suggestive evidence of a probiotic-induced improvement in working memory, and prebiotic-induced impairment in processing speed. However, the evidence remains inconclusive regarding any cognitive benefit or harm induced by the probiotic, prebiotic diet, or synbiotic treatments. Larger intervention studies are recommended, with inclusion of neuroimaging or electrophysiology measures. Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN12617000795392; registered 31 May 2017).
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