Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial

Abstract

Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.

Fig. 1. Participant flow diagram.

Flow of participants through the trial, including assessment for eligibility, randomisation, follow-up and analysis.

Fig. 2. Twin-paired group comparisons between prebiotic and placebo supplements, including data from the end of the study or the difference between baseline and end of study.

Paired group comparison of relative abundance (a) and prevalence (p) of bacterial taxa between study arms cross-sectionally or at study end adjusted for baseline taxon abundances. Testing for differences in microbiome taxon abundances was performed with a linear regression framework with a compositional bias correction based on LinDA. There were no significant differences between groups at baseline or for gut metabolic modules, gut–brain modules, or alpha diversity. Effect sizes are the bias-corrected coefficients from the linear models where positive effect sizes (blue) indicate higher levels in the placebo group and negative effect sizes (red) indicate higher levels in the prebiotic group.

Fig. 3. Study flowchart.

Caption: This flowchart was previously published in the study protocol. Reproduced with permission from Ni Lochlainn et al..