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

Mary Ni Lochlainn*, Carolyn Greig, Stephen Harridge, Claire J. Steves*, Ailsa Welch, Ruth C E Bowyer, Paul Seed

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.
Original languageEnglish
Article number1859
Number of pages15
JournalNature Communications
Volume15
DOIs
Publication statusPublished - 29 Feb 2024

Bibliographical note

Acknowledgements
The authors would like to acknowledge the National Institute of Health Research for funding this research. We would also like to acknowledge the research staff at the Department of Twin Research and all the participants. We particularly would like to thank Deborah Hart, Ayrun Nessa, Alyce Sheedy, and Gulsah Akdag who contributed a huge amount to the running of the PROMOTe trial. We thank the TwinsUK Volunteer Advisory Panel for their insightful comments and feedback regarding the study design. We would also like to thank Roosa Varjus for contributing to the microbiome analysis. This study was co-sponsored by Kings College London and Guy’s and St Thomas’ NHS Trust. Neither sponsor had any role in study design, data collection and analysis or manuscript writing. Funding MNL is supported by an NIHR Doctoral Fellowship (grant code: NIHR300159). C.J.S. receives funds from the Medical Research Council (MRC), Wellcome Trust (grant code WT 212904/Z/18/Z), and the Chronic Disease Research Foundation. K.W. has received funds from the MRC, NIHR, Crohn’s and Colitis UK, Kenneth Rainin Foundation, Leona M. and Harry B. Helmsley Charitable Trust, Almond Board of California, Danone, and International Dried Fruit Council. TwinsUK is funded by the Wellcome Trust, Wellcome LEAP, the Medical Research Council, Versus Arthritis, Engineering & Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, European Commission, Chronic Disease Research Foundation (CDRF), Zoe Ltd., the National Institute for Health and Care Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. The myfood24 dietary reporting software was used in this study. myfood24 was developed through Medical Research Council funding, grant G110235. myfood24 is now being supported by spinout company Dietary Assessment Ltd. Requests to use myfood24 should be made to [email protected].

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