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Muscle health declines during aging. One factor that may impact muscle health is the community of bacteria that live in our intestines, but studies aimed at improving muscle health by targeting the gut in older adults are sparse. The primary goal of this study is to use a diet that is enriched in soluble fiber, which is exclusively utilized by gut bacteria to make substances that can impact muscle health, to improve muscle-related measures in older adults.
During aging, skeletal muscle mass and physical function decrease, whereas levels of lipids and adipocytes increase within and between muscle cells, thereby worsening muscle composition. As a result of these age-related changes, older adults are at a higher risk for frailty, falls and fracture, disability and hospitalization, and all-cause mortality. Accordingly, elucidation of mechanisms that underlie muscle mass, muscle composition, and physical function, and interventions that positively affect these variables will be important for addressing the public health priority of an improved quality of life and healthy aging in older adults.
The gut microbiome and its metabolic products are involved in mechanisms that impact skeletal muscle mass, muscle composition, and physical function, which has been defined as the gut-muscle axis. For example, muscle mass and physical function are reduced in animals that do not have a microbiome (germ-free mice), and in antibiotic-treated mice, an intervention that reduces gut bacterial content. Investigating further, gut bacteria-derived metabolites affect muscle mass, muscle composition, and physical function in young and aged animals, including positive effects for the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate, and negative effects for indoxyl sulfate (IS) and para-cresol sulfate (PCS). Similarly, phenol sulfate (PS) and phenylacetylglutamine (PAG) are gut microbiome-derived metabolites that were associated with poor muscle composition and worse physical function in studies of older adult humans that were published by our group. Interestingly, higher colonic levels of SCFAs are associated with a lower pH, an important finding because growth of Enterobacteriaceae, a bacterial family that contains genes involved in the production of IS, PCS, PS, and PAG, is limited in an acidic environment and following exposure to physiological levels of SCFAs. Taken together, these data suggest that interventions aimed at increasing bacterial SCFA production may be an important approach for improving muscle-related measures in older adults.
Soluble fiber fermentation by gut bacteria results in the formation of acetate, propionate, and butyrate, and fecal SCFAs proportionally increase, whereas circulating levels of IS and PCS are reduced in response to high-soluble fiber diets. As a proof of concept, fecal and circulating levels of SCFAs, muscle mass, and aerobic exercise capacity were increased in young mice that were fed a relatively higher soluble fiber diet, but few studies have attempted this approach in older adult humans. When considering that fecal levels of SCFAs decrease during aging, whereas plasma levels of IS, PCS, PS, and PAG increase, these data collectively suggest that a high-soluble fiber diet may be an important approach for improving muscle-related measures in older adults humans. To test this hypothesis, older adults will be randomized to consume a high- or low-soluble fiber diet for 12-weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low-soluble fiber diet | Other |
| |
| High-soluble fiber diet | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low-soluble fiber diet | Other | 12 older adults (>65y) will be randomized to consume the USDA Guidelines for fiber intake (10g of total fiber/1000 calories), as the low-soluble fiber diet |
| Measure | Description | Time Frame |
|---|---|---|
| Quantification of SCFAs in fecal samples | Fecal levels of bacterial metabolites, including acetate, propionate, and butyrate will be determined at the baseline and week-13 study visits | Change from baseline when compared with the Week-13 visit |
| Quantification of whole-body lean mass with DXA | Measurement of whole-body lean mass will be determined at the baseline and week-13 study visits | Change from baseline when compared with the Week-13 visit |
| Quantification of hand grip strength | Grip strength will be determined at the baseline and week-13 study visits | Change from baseline when compared with the Week-13 visit |
| Chair stand test | The number of chair stands that can be performed in 30 seconds will be determined at the baseline and week-13 study visits | Change from baseline when compared with the Week-13 visit |
| Measure | Description | Time Frame |
|---|---|---|
| Quantification of thigh muscle composition with computed tomography | Determined at the baseline and week-13 study visits | Change from baseline when compared with the Week-13 visit |
| 6-minute walk test |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael S Lustgarten, PhD | Scientist II, NEPS Laboratory | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jean Mayer Human Nutrition Research Center on Aging at Tufts University | Boston | Massachusetts | 02111 | United States |
No data from participants will be shared with researchers not affiliated with this project.
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| ID | Term |
|---|---|
| D055948 | Sarcopenia |
| D003141 | Communicable Diseases |
| ID | Term |
|---|---|
| D009133 | Muscular Atrophy |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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24 older adults (> 65y) will be randomized to consume a high- or low-soluble fiber diet
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| High-soluble fiber diet | Other | 12 older adults (>65y) will be randomized to consume 34-35g of total fiber/1000 calories, as the high-soluble fiber diet |
|
The distance walked in 6 minutes will be determined at the baseline and week-13 study visits
| Change from baseline when compared with the Week-13 visit |
| Quantification of gut bacterial metabolites in plasma | Bacterial metabolites, including SCFAs but also indoxyl sulfate, p-cresol sulfate, phenol sulfate, and phenylacetylglutamine will be determined at the baseline and week-13 study visits | Change from baseline when compared with the Week-13 visit |
| Quantification of gut bacterial composition in fecal samples | Determined at the baseline and week-13 study visits | Change from baseline when compared with the Week-13 visit |
| Quantification of pH in fecal samples | Determined at the baseline and week-13 study visits | Change from baseline when compared with the Week-13 visit |
| D001284 | Atrophy |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D007239 | Infections |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |