Impact of Diet on the Gut-Muscle Axis in Older Adults

Impact of a High-Soluble Fiber Diet on the Gut-Muscle Axis in Older Adults

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.

Study Overview

• Status: Completed
• Conditions: Sarcopenia; Microbial Colonization; Dietary Exposure
• Intervention / Treatment: Other: Low-soluble fiber diet; Other: High-soluble fiber diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Jean Mayer Human Nutrition Research Center on Aging at Tufts University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Independently living older adults (> 65y)
2. Sedentary (Godin-Shepard Leisure Time Physical Activity Questionnaire score < 10)
3. Non-smoking
4. Not already consuming a high-fiber diet (> 22, 28 g/day for women, men)
5. Free of gastrointestinal disease (gastrointestinal cancer, inflammatory bowel disease, bariatric surgery, irritable bowel syndrome)
6. Fluent in English
7. Willing to attend three study visits (enrollment, baseline, and week-13)
8. Willing to consume an abundance of fruits, vegetables, nuts/seeds
9. Willing to consume an abundance of soluble fiber-rich foods (broccoli, brussels sprouts, flaxseeds sweetened with dates, lima beans, butternut squash, carrots, collard greens)
10. Willing to tolerate mild gastrointestinal discomfort (bloating, belly grumbling, flatulence). Note that all attempts will be made to replace foods that may trigger these issues.
11. Willing to not consume antibiotics during the 13-week study
12. Willing to not schedule a colonoscopy during the 13-week study

Exclusion Criteria:

1. Unwilling to visit the Tufts Human Nutrition Research Center on Aging (HNRCA) 3x/week to pick up the pre-prepared study diet
2. Unwilling to only consume the provided food (unsweetened tea and/or black coffee are allowed)
3. Food allergies related to foods that are included in the study
4. Chewing problems
5. Unwilling to wear a daily step counter (pedometer)
6. Unwilling to complete a daily questionnaire that will assess gastrointestinal comfort
7. Malnutrition (BMI < 18.5 kg/m2)
8. Use of supplemental probiotics or antibiotics, participation in an investigational drug evaluation, or a recent change in habitual medication use within the 1 month-period prior to the screening visit
9. > 5% weight loss or weight gain within the past 6-months
10. A recent history of alcohol abuse (within the past 5 years)
11. A history of any significant injury or surgery that currently affects physical functioning and ability to perform physical function testing
12. Treatment with immunosuppressive drugs
13. A prior diagnosis of organ failure (heart, liver, renal, respiratory)
14. Diabetes mellitus (type 1, or type 2 with insulin therapy)
15. Chronic kidney disease (eGFR ≤ 30 mL/min/1.73 m2)
16. Overt disease (cancer, dementia, cardiovascular disease)
17. Chronic use of anti-inflammatory medication (corticosteroids)
18. Already enrolled in another research study
19. Active infection, including Tuberculosis , HIV, malaria, hepatitis, shingles, Methicillin-Resistant Staphylococcus Aureus (MRSA), SARS-CoV-2
20. Any major illness or condition that may interfere with study outcomes at the discretion of the study physician
21. Won't remain in Boston for the 13-week study duration
22. Unwilling to complete a daily checklist aimed at quantifying the amount of food eaten on the study diet

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Low-soluble fiber diet	Other: Low-soluble fiber diet; 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
Active Comparator: High-soluble fiber diet	Other: High-soluble fiber diet; 12 older adults (>65y) will be randomized to consume 34-35g of total fiber/1000 calories, as the high-soluble fiber diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Tufts University
• Investigators: Study Director: Michael S Lustgarten, PhD, Scientist II, NEPS Laboratory

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): April 30, 2025

Study Registration Dates

• First Submitted: August 24, 2022
• First Submitted That Met QC Criteria: September 16, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Actual): July 18, 2025
• Last Update Submitted That Met QC Criteria: July 15, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: microbiome; skeletal muscle; SCFA; soluble fiber; gut-muscle axis; Uremic metabolites
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Pathologic Processes; Pathological Conditions, Anatomical; Disease Attributes; Muscular Atrophy; Atrophy; Infections; Communicable Diseases; Sarcopenia
• Other Study ID Numbers: GRANT13386865

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No data from participants will be shared with researchers not affiliated with this project.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No