Protein and Skeletal Muscle in Older Twins: Role of the Gut Microbiome

Dietary Protein and Skeletal Muscle in Older Twins - Targeting the Gut Microbiome to Overcome Anabolic Resistance: The PROMOTe Study

Research Question: Does the gut microbiome contribute to muscle anabolic resistance to protein supplementation in older adults?

Background: Loss of muscle occurs with age and skeletal muscle in older adults can display anabolic resistance to protein in diet. It has been hypothesised that the gut microbiome may play a role in this relationship and therefore could be targeted.

Aim:

This trial aims to test whether modulation of the gut microbiome, in addition to protein supplementation, can improve skeletal muscle function versus protein supplementation alone.

Methods:

Double blinded, randomised, placebo controlled, dietary intervention study. Twin pairs will be randomised to either receive protein supplementation plus placebo or protein supplementation plus a gut microbiome modulator (prebiotic plus probiotic) for 12 weeks. Primary outcome will be muscle function measured using chair-rise time.

Conclusion:

Anabolic resistance warrants further characterisation to guide future therapeutic interventions, especially considering its role in the development of disability, sarcopenia and frailty.

Research Question: Does the gut microbiome contribute to muscle anabolic resistance to protein supplementation in older adults?

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 respond as well as younger people to protein, so called 'anabolic resistance'. The aetiology and molecular mechanisms for this are not understood, however a number have been proposed. The gut microbiome is known to play a key role in a number of these postulated mechanisms. This has led us to hypothesise that the gut microbiome may mediate anabolic resistance and could represent an exciting new target for ameliorating muscle loss in older adults.

Aim:

This trial aims to test whether modulation of the gut microbiome, in addition to protein supplementation, can improve skeletal muscle function versus protein supplementation alone.

Methods:

Double blinded, randomised, placebo controlled, dietary intervention study. Volunteers will be recruited in twin pairs from TwinsUK cohort, for which extensive baseline data are available. The twin nature of the study allows for close genetic and environmental matching at baseline. Each pair will be randomised to either receive protein supplementation plus placebo or protein supplementation plus a gut microbiome modulator (prebiotic plus probiotic). Intervention period will be 12 weeks. Clinical and biochemical measures will be taken at 0, and 12 weeks, with 2-monthly contact. Gut microbiota composition will be measured, alongside a battery of physical assessments. Primary outcome will be muscle function measured using chair-rise time. The trial will be delivered remotely using video calls, and postal boxes.

Conclusion:

Anabolic resistance warrants further characterisation to guide future therapeutic interventions, especially considering its role in the development of disability, sarcopenia and frailty. Therapeutic options are badly needed, particularly for older adults who cannot undertake exercise programmes.

Inclusion Criteria:

• Aged >=60 years
• Dietary protein intake of <1.3g/kg/day
• Able to consent
• Able to access video calls on a device such as laptop/tablet

Exclusion Criteria:

• Severe food allergy
• Current or recent antibiotic use (preceding 3 months)
• Currently or recent use of protein or leucine supplements (preceding 3 months)
• Currently or recent use of probiotic or prebiotic food supplements (preceding 3 months)
• Current or prior history of gastrointestinal disease e.g. gastrointestinal cancer, inflammatory bowel disease, bariatric surgery, irritable bowel syndrome
• history of any significant injury or surgery which currently affects physical functioning and ability to undertake chair stand test
• weight loss of ≥5% of body weight in preceding 6-12 months
• Currently involved in other intervention studies
• Any condition or circumstance likely to interfere with the normal conduct of the study and interpretation of the results, as judged by the investigators As the study population are over 60 years old, it is assumed that there will be no pregnant women who are eligible to take part.