Distinct Exercise Modalities on Gut Microbiome
NCT Number: NCT06545123
Acronym: DEMGUTS
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Sarcopenia|Older Adults
Interventions: BEHAVIORAL: Concurrent exercise training
Sponsor: Faculty of Sports- Research Center in Physical Activity, Health and Leisure
Collaborators: Unit for Multidisciplinary Research in Biomedicine
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 69
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2024-09-01
Completion Date: 2025-06-30

Summary:
Sarcopenia is a multifactorial muscular disease with detrimental clinical consequences, impairing physical function, functional independence, quality of life, need for long-term care and premature mortality. The development of sarcopenia is influenced by a complex interaction of multiple environmental and endogenous factors. However, to date, these complex mechanisms were unable to fully explain sarcopenia adverse health outcomes on skeletal muscle mass and function in older adults. Recently, the gut microbiome and its gut-derived metabolites have emerged as a key player in sarcopenia, with evidence suggesting that influence many underlying pathophysiological mechanisms (i.e., immune and inflammation system, anabolic resistance, insulin sensitivity, and energy production) that are involved in the development of sarcopenia. Current treatment guidelines of sarcopenia reinforce the role of exercise training, particularly resistance training to prevent adverse health outcomes. Exercise also stimulates favorable changes in gut microbiome composition and function, leading to host health benefits, regardless of nutrition. Nonetheless, the effects of exercise training on gut microbiome in patients with sarcopenia remains unclear, with existing evidence derived mainly from observational studies. In addition, the available evidence suggests that different types of exercise modalities may elicit distinct changes in gut microbiota composition but, to date, no study specifically addressed the optimal type of exercise modality in older adults considering the impact of gut microbiota composition or of gut-derived metabolites. Thus, despite the growing body of literature on the gut-muscle axis and sarcopenia, evidence from comparative studies focused on different exercise training regimens with a randomized controlled trial design in the impact of gut microbiota on skeletal muscle mass and function in sarcopenic patients is still lacking. Given that aerobic and resistance exercise stimulate different bioenergetic mechanisms and metabolic signaling pathways, we hypothesize that gut microbiome composition may be differently modulated by these distinct exercise regimens and that differently impact skeletal muscle mass and function, and physical performance in older adults. Leveraging current recruitment, logistics and human resources from a community exercise training program and the internal institutional collaborations, the investigative team will build a consecutive line of research to fill this literature gap and explore the impact of different exercise regimens on gut microbiome composition and gut-derived metabolites in these patients. The research team will start with a pilot single center 3-parallel arm open-label randomize control trial. Participants that meet the inclusion/exclusion criteria will be randomly assigned to: i) moderate aerobic exercise (AER); ii) resistance exercise (RES); or iii) concurrent exercise training (RES+AER). Participants in the experimental groups will engage in a supervised center-based exercise intervention (12-weeks, 3d/w, 60min/d). All participants will be assessed at i) baseline, ii) end of intervention (14 weeks) and iii) at close-out (26-weeks). The primary outcome will be the change in the relative abundance of Faecalibacterium prausnitzii and other SCFA producing bacteria after the intervention (14-weeks). Secondary outcomes include 1) change of Faecalibacterium prausnitzii relative abundance at close-out (26 weeks); 2) change of relative abundance of Lactobacillus and Bifidobacterium genera after the intervention and at the end of the follow-up. A set of complementary outcomes will also be assessed to broadly characterize the impact of each exercise intervention, including body composition, skeletal muscle function, functional performance and general gut microbiome composition. Other important confounding outcomes will be evaluated, including nutritional intake, daily physical activity, medication and supplementation use, and associated comorbidities. In the long term, the study team expects to contribute to clinical guidance and exercise prescription in older adults with sarcopenia using an evidence-based approach by exploring the optimal exercise mode to elicit favorable gut and skeletal muscle health benefits.

Primary Outcome Measures: Percent change in the relative abundance of Faecalibacterium prausnitzii and other SCFA producing bacteria, The primary outcome will be the percent change in the relative abundance of Faecalibacterium prausnitzii and other SCFA producing bacteria after the intervention (14-weeks) using next generation sequencing on faecal samples, 14-weeks
Secondary Outcome Measures: Percent change of Faecalibacterium prausnitzii relative abundance at close-out, Percent change of Faecalibacterium prausnitzii relative abundance at close-out (26-weeks)using next generation sequencing on faecal samples;, 26- weeks|Percent change of relative abundance of Lactobacillus and Bifidobacterium genera after the intervention and at the end of the follow-up, Percent change of relative abundance of Lactobacillus and Bifidobacterium genera after the intervention using next generation sequencing on faecal samples, 26- weeks
Other Outcome Measures: Body composition, Body composition will be assessed by whole-body dual-energy X-ray absorptiometry to measure percent body fat mass, percent lean mass, appendicular lean mass, 14- weeks|Skeletal muscle function, Dominant lower limb knee extension and flexion muscle strength will be assessed through a isokinetic dynamometer to measure peak torque of extension and flexion total work (J), 14-weeks|Nutritional Intake, Participants will be instructed to record all food and beverage intake for three consecutive days using a 3-day food diary prior to the fecal collection day, 14-weeks|Physical performance, participants will be evaluated using gait speed, the 30-second chair rise, the Short Physical Performance Battery (SPPB) and the 400 meter walk test. To assess gait speed, we will use the 4-meter usual walk test with speed time. The SPPB is a composite test battery that includes assessment of gait speed, a balance test, and a chair stand test. Each test is scored 4 points until a maximum score of 12 points. the 400-meter walk test, participants are asked to complete 20 laps of 20 m, each lap as fast as possible. This test evaluates walking ability and endurance., 14-weeks