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

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.

Sarcopenia Is a Cause and Consequence of Metabolic Dysregulation in Aging Humans: Effects of Gut Dysbiosis, Glucose Dysregulation, Diet and Lifestyle

“…A few studies have been conducted to examine the effects of prebiotics on skeletal muscle mass and muscle strength through changing gut microbiota [121]. A study in elderly human subjects evaluated the effects of consuming a prebiotic supplement consisting of inulin and fructooligosaccharide, which would be expected to promote a healthy microbiome [122,123]. They reported that the subjects having the prebiotic had greater hand strength and endurance than control subjects, although they did not report the effects on the microbiome [122,123].…”

“…A study in elderly human subjects evaluated the effects of consuming a prebiotic supplement consisting of inulin and fructooligosaccharide, which would be expected to promote a healthy microbiome [122,123]. They reported that the subjects having the prebiotic had greater hand strength and endurance than control subjects, although they did not report the effects on the microbiome [122,123]. Vegan diets rich in dietary fibers are associated with rich Prevotella and high microbial diversity, and Prevotella has been associated with high-carbohydrate and high-fiber diets [70].…”

Interventions on Gut Microbiota for Healthy Aging

“…It is known that older people present an 'anabolic resistance', that is, the inability to anabolize muscle in response to protein supplementation. The modulation of the gut microbiome using a prebiotic, in addition to protein supplementation, can improve muscle strength supplementation alone [102], suggesting new aids to mitigate sarcopenia and frailty in older adults.…”

Effects of anti-aging interventions on intestinal microbiota

“…Those who take prebiotic and protein supplements have a greater improvement in muscle strength than those who take protein supplements alone. 137 …”