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

Mary Ni Lochlainn, Ruth C E Bowyer, Janne Marie Moll, María Paz García, Samuel Wadge, Andrei-Florin Baleanu, Ayrun Nessa, Alyce Sheedy, Gulsah Akdag, Deborah Hart, Giulia Raffaele, Paul T Seed, Caroline Murphy, Stephen D R Harridge, Ailsa A Welch, Carolyn Greig, Kevin Whelan, Claire J Steves

Journal: Nature communications 2024;15(1):1859

PMID: 38424099

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Plain Language Summary

Humans lose skeletal muscle with advancing age, and this can progress to sarcopenia. Dietary protein is crucial for maintaining skeletal muscle health; however, several factors can lead to reduced protein intake in older age. The aim of this study was to test whether the addition of gut microbiome modulation could augment established muscle function improvements from combined protein (branched chain amino acids [BCAA]) and resistance exercise. This study was based on the PROMOTe (effect of PRebiotic and prOtein on Muscle in Older Twins) trial which was a randomised controlled trial in which twin pairs (n= 72) were randomised, one twin to each study arm. Results showed that prebiotics improved cognition but did not impact muscle strength and function, compared with placebo. Furthermore, gut microbiome modulation via prebiotic supplementation in the context of ageing-muscle research is feasible and well tolerated, with clear responses noted in the gut microbiota composition and function. Authors concluded that cheap and readily available gut microbiome interventions hold promise for improving cognitive frailty in our ageing population.

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.

Address: King's College London, Department of Twin Research and Genetic Epidemiology, London, SE1 7EH, UK. [email protected].; King's College London, Department of Twin Research and Genetic Epidemiology, London, SE1 7EH, UK.; The Alan Turing Institute, London, NW1 2DB, UK.; Clinical Microbiomics, Copenhagen, Denmark.; King's College London, Department of Twin Research and Genetic Epidemiology, London, SE1 7EH, UK.; GKT School of Medical Education, King's College London, London, UK.; Unit for Medical Statistics/Department for Women and Children's Health, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.; King's Clinical Trials Unit, Research Management and Innovation Directorate, King's College London, London, UK.; Centre for Human & Applied Physiological Sciences, King's College London, London, UK.; Department of Epidemiology and Public Health, Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK.; School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.; MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Birmingham, UK.; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK.; King's College London, Department of Nutritional Sciences, Franklin Wilkins Building, SE1 9NH, London, UK.; King's College London, Department of Twin Research and Genetic Epidemiology, London, SE1 7EH, UK. [email protected].

DOI: 10.1038/s41467-024-46116-y

Patient Centred Factor

Mediators: Gut microbiome

Physical Environment

Infectious Agents

Clinical Imbalances

Neurological Structural Integrity and Musculoskeletal

Modifiable Lifestyle Factors

Diet

Jadad Score

Allocation Concealment

Yes

Nutrition Evidence Keywords

Microbiota Gut microbiome Resistance exercise Amino acids Prebiotic Appetite Dietary Protein

Bioactive Substances

Prebiotics

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MeSH Terms: Aged, Humans, Aging, Cognition, Dietary Supplements, Double-Blind Method, Gastrointestinal Microbiome, Muscles, Muscular Diseases, Middle Aged