The PROMOTe study: targeting the gut microbiome with prebiotics to overcome age-related anabolic resistance: protocol for a double-blinded, randomised, placebo-controlled trial

Mary Ni Lochlainn, Ayrun Nessa, Alyce Sheedy, Rachel Horsfall, María Paz García, Deborah Hart, Gulsah Akdag, Darioush Yarand, Samuel Wadge, Andrei-Florin Baleanu, Kevin Whelan, Claire Steves, Mary Ni Lochlainn, Ayrun Nessa, Alyce Sheedy, Rachel Horsfall, María Paz García, Deborah Hart, Gulsah Akdag, Darioush Yarand, Samuel Wadge, Andrei-Florin Baleanu, Kevin Whelan, Claire Steves

Abstract

Background: Loss of skeletal muscle mass and strength occurs with increasing age and is associated with loss of function, disability, and the development of sarcopenia and frailty. Dietary protein is essential for skeletal muscle function, but older adults do not anabolise muscle in response to protein supplementation as well as younger people, so called 'anabolic resistance'. The aetiology and molecular mechanisms for this are not understood, however the gut microbiome is known to play a key role in several of the proposed mechanisms. Thus, we hypothesise that the gut microbiome may mediate anabolic resistance and therefore represent an exciting new target for ameliorating muscle loss in older adults. This study aims to test whether modulation of the gut microbiome using a prebiotic, in addition to protein supplementation, can improve muscle strength (as measured by chair-rise time) versus protein supplementation alone.

Methods: The study is a randomised, double-blinded, placebo-controlled trial, with two parallel arms; one will receive prebiotic and protein supplementation, and the other will receive placebo (maltodextrin) and protein supplementation. Participants will be randomised as twin pairs, with one twin from each pair in each arm. Participants will be asked to take supplementation once daily for 12 weeks in addition to resistance exercises. Every participant will receive a postal box, containing their supplements, and the necessary equipment to return faecal, urine, saliva and capillary blood samples, via post. A virtual visit will be performed using online platform at the beginning and end of the study, with measures taken over video. Questionnaires, food diary and cognitive testing will be sent out via email at the beginning and end of the study.

Discussion: This study aims to provide evidence for the role of the gut microbiome in anabolic resistance to dietary protein. If those who take the prebiotic and protein supplementation have a greater improvement in muscle strength compared with those who take protein supplementation alone, this would suggest that strategies to modify the gut microbiome may reduce anabolic resistance, and therefore potentially mitigate sarcopenia and frailty in older adults.

Trial registration: Clinicaltrials.gov: NCT04309292 . Registered on the 2nd May 2020.

Keywords: Ageing; Anabolic resistance; Gut microbiome; Muscle; Sarcopenia.

Conflict of interest statement

CJS receives funds from the MRC, Wellcome Trust, and the Chronic Disease Research Foundation. KW receives funds from MRC, NIHR, Crohn’s & Colitis UK, Kenneth Rainin Foundation, Leona M and Harry B Helmsley Charitable Trust, Almond Board of California, Danone, International Dried Fruit Council.

No other authors report any competing interests.

References

    1. Nations U, of Economic D, Affairs S, Division P. World Population Ageing. Highlights; 2019.
    1. Office for National Statistics. Population estimates for the UK, England and Wales, Scotland and Northern Ireland [Internet]. Statistical bulletin. 2017 [cited 2018 Sep 5]. Available from: .
    1. Kingston A, Wohland P, Wittenberg R, Robinson L, Brayne C, Matthews FE, et al. Is late-life dependency increasing or not? A comparison of the Cognitive Function and Ageing Studies (CFAS). Lancet [Internet]. 2017 [cited 2018 Sep 13];390:1676–84. Available from: .
    1. Welch AA. Nutritional influences on age-related skeletal muscle loss. Proc Nutr Soc. 2014;73(1):16–33. doi: 10.1017/S0029665113003698.
    1. Rejc E, Floreani M, Taboga P, Botter A, Toniolo L, Cancellara L, et al. Loss of maximal explosive power of lower limbs after 2 weeks of disuse and incomplete recovery after retraining in older adults. J Physiol [Internet]. 2018 Feb 15 [cited 2018 Jun 18];596(4):647–65. Available from: 10.1113/JP274772.
    1. Houston DK, Nicklas BJ, Ding J, Harris TB, Tylavsky FA, Newman AB, et al. Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study. Am J Clin Nutr 2008;87150–5. 2008;87:150–5.
    1. Ni Lochlainn M, Bowyer RCE, Steves C. Dietary Protein and Muscle in Aging People: The Potential Role of the Gut Microbiome. Nutrients [Internet]. 2018 Jul 20 [cited 2018 Aug 8];10(929). Available from: /2072-6643/10/7/929.
    1. Morris S, Cater JD, Green MA, Johnstone AM, Brunstrom JM, Stevenson EJ, et al. Inadequacy of protein intake in older UK adults. Geriatr [Internet]. 2020 Mar 1 [cited 2020 Oct 1];5(1). Available from: /pmc/articles/PMC7151458/?report = abstract.
    1. Deutz NEP, Bauer JM, Barazzoni R, Biolo G, Boirie Y, Bosy-Westphal A, et al. Protein intake and exercise for optimal muscle function with aging: Recommendations from the ESPEN Expert Group. Clin Nutr 2014. 2014;33(6):929–36.
    1. Tieland M, Borgonjen-Van Den Berg KJ, Van Loon LJC, De Groot LCPGM. Dietary protein intake in community-dwelling, frail, and institutionalized elderly people: Scope for improvement. Eur J Nutr. 2012;51(2):173–9. doi: 10.1007/s00394-011-0203-6.
    1. Vigotsky AD, Schoenfeld BJ, Than C, Brown JM. Methods matter: The relationship between strength and hypertrophy depends on methods of measurement and analysis. PeerJ. 2018;(6).
    1. Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, et al Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians. Ahmed N, editor. PLoS One [Internet]. 2010 May 17 [cited 2018 Jun 22];5(5):e10667. Available from: 10.1371/journal.pone.0010667.
    1. Ridaura VK, Faith JJ, Rey FE, Cheng J, Alexis E, Kau AL, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science (80-) [Internet]. 2013;341(6150):1241214. Available from: .
    1. Smith P, Willemsen D, Popkes ML, Metge F, Gandiwa E, Reichard M, et al. Regulation of Life Span by the Gut Microbiota in The Short-Lived African Turquoise Killifish. bioRxiv [Internet]. 2017 Mar 27 [cited 2018 Jun 5];120980. Available from: .
    1. Gibson GR, Hutkins RW, Sanders ME, Prescott SL, Reimer RA, Gibson GR;, et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) Consensus Statement on the Definition and Scope of Prebiotics. Nat Rev Gastroenterol Hepatol [Internet]. 2017 [cited 2019 Dec 10];14:491–502. Available from: .
    1. Buigues C, Fernández-Garrido J, Pruimboom L, Hoogland AJ, Navarro-Martínez R, Martínez-Martínez M, et al. Effect of a Prebiotic Formulation on Frailty Syndrome: A Randomized, Double-Blind Clinical Trial. Int J Mol Sci [Internet]. 2016 Jun 14 [cited 2018 Jun 5];17(932):932. Available from: .
    1. Theou O, Jayanama K, Fernández-Garrido J, Buigues C, Pruimboom L, Hoogland AJ, et al. Can a Prebiotic Formulation Reduce Frailty Levels in Older People? J frailty aging. 2019;8(1):48–52.
    1. Verdi S, Abbasian G, Bowyer RCE, Lachance G, Yarand D, Christofidou P, et al. TwinsUK: The UK Adult Twin Registry Update. Twin Res Hum Genet. 2019 Sep;17:1–7.
    1. Bohannon RW. Sit-to-Stand Test for Measuring Performance of Lower Extremity Muscles. Percept Mot Skills [Internet]. 1995 Feb 4 [cited 2021 Apr 23];80(1):163–6. Available from: 10.2466/pms.1995.80.1.163.
    1. Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, et al. A short physical performance battery assessing lower extremity function: Association with self-reported disability and prediction of mortality and nursing home admission. Journals Gerontol [Internet]. 1994 [cited 2019 Nov 14];49(2):M85–94. Available from: .
    1. Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ [Internet]. 2005 Aug 30 [cited 2020 Aug 28];173(5):489–95. Available from: .
    1. Robbins TW, James M, Owen AM, Sahakian BJ, McInnes L, Rabbitt P. Cambridge Neuropsychological Test Automated Battery (CANTAB): A Factor Analytic Study of a Large Sample of Normal Elderly Volunteers. Dement Geriatr Cogn Disord [Internet]. 1994 [cited 2021 Apr 23];5(5):266–81. Available from: .
    1. Wilson M-MG, Thomas DR, Rubenstein LZ, Chibnall JT, Anderson S, Baxi A, et al. Appetite assessment: simple appetite questionnaire predicts weight loss in community-dwelling adults and nursing home residents. Am J Clin Nutr [Internet]. 2005 Nov 1 [cited 2021 Apr 23];82(5):1074–81. Available from: .
    1. Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, et al. International physical activity questionnaire: 12-Country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381–95. doi: 10.1249/01.MSS.0000078924.61453.FB.
    1. RStudio Team . RStudio: Integrated Development for R. Boston: RStudio, Inc.; 2015.
    1. Walker SN, Pullen CH, Hageman PA, Boeckner LS, Hertzog M, Oberdorfer MK, et al. Maintenance of activity and eating change after a clinical trial of tailored newsletters with older rural women. Nurs Res. 2010 Sep;59(5):311–21.
    1. Cesari M, Kritchevsky SB, Newman AB, Eleanor M, Harris TB, Penninx BW, et al. Added Value of Physical Performance Measures in Predicting Adverse Health-Related Events: Results from the Health, Aging, and Body Composition Study. J Am Geriatr Soc [Internet]. 2009 Feb [cited 2018 Nov 8];57(2):251–9. Available from: .
    1. Harvey NC, Odén A, Orwoll E, Lapidus J, Kwok T, Karlsson MK, et al. Measures of Physical Performance and Muscle Strength as Predictors of Fracture Risk Independent of FRAX, Falls, and aBMD: A Meta-Analysis of the Osteoporotic Fractures in Men (MrOS) Study. J Bone Miner Res. 2018 Dec 1;33(12):2150–7.

Source: PubMed

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