66 The PROMOTe study: prebiotic supplementation improves cognition versus placebo in healthy older twins

Abstract Background There is a growing body of evidence linking the microbiota in the human gut, to the brain and to physical function. Animal and human studies have shown that inducing changes in the microbiota can alter muscle physiology and cognitive behaviour, indicating causative pathways. The PROMOTe trial aimed to test whether the gut microbiome mediates anabolic resistance to protein in older adults. A secondary objective was to test whether modulation of the gut microbiome using a pre-biotic food supplement, improved cognition versus placebo. Methods This placebo-controlled double-blinded randomised controlled trial used twin pairs, recruited from the TwinsUK cohort. Those aged > = 60, with low baseline protein intake, and access to a computer (due to remote trial delivery) were included. One twin received protein supplementation plus placebo and the other received protein supplementation plus a gut microbiome modulator (prebiotic). Intervention period was 12 weeks. Participants were advised to take 1 supplement sachet daily, and to undertake resistance exercises. The primary outcome was muscle strength as measured using chair-rise time. Cognition (CANTAB battery) was a secondary outcome. Linear mixed effects regression models were used to compare intervention groups (arm 1 vs arm 2; blinded). Twin clustering was considered as random effects, both family identifier and zygosity, and treatment group as fixed effect. Results Target sample size was 70 individuals. We screened 626 and randomised 72 participants (36 pairs). More adverse events occurred in the prebiotic group (n = 8 versus n = 2 in placebo group; p = 0.041), but compliance remained high in both groups (% adherence >78% in each group; p = 0.37). There was no significant difference between arms for the primary outcome of chair rise time (coefficient 0.184; 95% CI -0.569-0.938; p = 0.631). The prebiotic intervention arm had an improved cognition factor score versus the placebo group (coefficient 0.482; 95% CI 0.823–0.141; p = 0.014). Conclusion Prebiotic food supplementation improves cognition versus placebo in a cohort of healthy older twins.