Probiotic-Muscle Study

Study Overview
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Brief Summary
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This study will examine the effect of probiotic supplementation (Bacillus coagulans) on muscle protein synthesis in older adults in response to a plant-based diet. The investigators hypothesize that probiotic supplementation will enhance the digestibility of plant protein, therefore increasing the proportion of ingested amino acids that appear in systemic circulation and enhancing rates of muscle protein synthesis.

Detailed Description
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There is increasing interest in the use of plant-based proteins, both from the perspectives of global sustainability and growing consumer markets; however, plant-based proteins are known to have lower digestibility and lower ability to stimulate muscle protein synthesis (an important determinant of muscle mass) compared with animal-based proteins. Emerging evidence indicates that the probiotic Bacillus coagulans GBI-30, 6086 (GanedenBC30) can enhance plant protein digestibility. As such, Bacillus coagulans treatment may augment rates of muscle protein synthesis in response to plant-based protein intake in humans, by increasing the proportion of ingested amino acids that appear in systemic circulation after a plant meal, as circulating amino acids act as both a trigger to stimulate muscle protein synthesis in humans as well as providing the building block for new muscle tissue. An increase in muscle protein synthesis rates would be particularly critical in older adults as it is well established that one of the key mechanisms driving the loss of muscle mass with age is a reduction in muscle protein synthesis rates in response to dietary protein intake. Therefore, if probiotic supplementation can improve muscle protein synthesis rates following plant protein consumption, this indicates it may represent an effective and environmentally sensitive strategy to attenuate adverse age-related loss of muscle mass and muscle function. This is critical as the maintenance of skeletal muscle health is an important factor in the preservation of independence and quality of life as we age.

Official Title
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Effect of Bacillus Coagulans on Skeletal Muscle Protein Synthesis in Response to Vegetable Protein Ingestion

Conditions
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Old Age; Debility, Muscle Weakness, Protein Deregulation, Protein Deposition

Intervention / Treatment
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* Dietary Supplement: Probiotic
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: ≥65 y Sex: males and female Body mass index (BMI) between 20-35 kg/m2 Non-smokers Generally healthy according to responses to a standard health screening questionnaire Exclusion Criteria: Cancer (malignancy in the past 5 years) CVD Chronic kidney disease Liver failure Diabetes or pre-diabetes Conditions that will affect the ability to consume, digest and/or absorb the study supplement (i.e. gastrointestinal disease) Smokers Excess alcohol intake Regular resistance training Total walking incapacity Musculoskeletal or neuromuscular impairments Medications interfering with muscle metabolism Ongoing probiotic supplementation Antibiotic use in the previous 6 weeks Significant body mass loss in the 1 month period prior to the study

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The study will be a randomised, double-blind, placebo-controlled crossover study. Each participant will undergo 8 weeks of Bacillus coagulans (probiotic) supplementation and 8 weeks of placebo supplementation in a counterbalanced order. There will be a 5-day trial period at the end of each supplementation phase. There will be a wash-out period of 8 weeks between probiotic and placebo supplementation.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Maltodextrin containing capsule | Other: Placebo<br>* Maltodextrin capsule, no active ingredient<br>|
| Experimental: Probiotic<br>Probiotic containing capsule | Dietary Supplement: Probiotic<br>* GanedenBC30 (Bacillus coagulans GBI-30, 6086) capsule made of 1 billion colony forming units (cfu). Description: pure cell mass of an L-(+) lactic acid-producing, gram-positive, spore-forming shaped bacterium that is aerobic to microaerophilic. Maltodextrin used as filler.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myofibrillar protein synthesis | Measured as fractional synthetic rate (%/day) over a 2-d period after each supplementation arm and in response to a plant-based diet | 6 months | 
| Pattern of change in plasma total amino acid, essential amino acid and leucine concentrations | Assessed via GC-MS. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in microbiome composition | Assessed in faecal samples via 16s rRNA analysis | 6 months | 
| Change in metabolome | Assesed in blood and faecal water via 600 MHz nuclear magnetic resonance (NMR) spectrometry | 6 months | 
| Changes in gut hormones | ELISA (enzyme-linked immunosorbent assay) | 6 months | 
| Changes in gut/digestion-related complaints | Assessed via the Gastrointestinal Symptom Rating Scale (GSRS), where minimum and maximum values are: no discomfort at all, and very severe discomfort respectively (higher score means worse outcome). | 6 months | 
| Changes in bowel movement | Assessed via the Bristol Stool chart, where average faecal appearance is indicated out of seven options available | 6 months | 
| Changes in strength | Assessed via handgrip strength using a handgrip dynamometer | 6 months | 
| Changes in immuno-surveillance | Assessed via the Common Cold Questonnaire (CCQ), where minimum and maximum values are: none, and severe respectively (higher score means worse outcome). | 6 months | 
| Changes in appetite | Assessed via the Visual Analogue Scale (VAS) during 3 days of the trial period and after the protein-containing beverage, where the left and right side of the scale indicate: not hungry at all, and extremely hungry respectively (there is not an assigned better or worse outcome for this scale) | 6 months |