MedPath

Age-associated Arterial Dysfunction, Western Diet, and Aerobic Exercise: Role of the Gut Microbiome

Not Applicable
Conditions
Aging
Interventions
Other: Western Diet
Other: Non-Western Diet
Registration Number
NCT03334201
Lead Sponsor
University of Colorado, Boulder
Brief Summary

The risk of developing cardiovascular diseases increases with aging largely due to age-related declines in the function of arteries (arterial dysfunction), which are influenced by common lifestyle factors such as consumption of a "Western" diet and lack of sufficient physical activity; thus, it is important to study how these factors interact to affect artery function. This study will determine whether changes to the gut microbiome (the collection of bacteria and other "microbes" living in the intestinal tract) with aging, Western diet consumption and aerobic exercise influence arterial function, and the biological pathways (mechanisms) involved. Specifically, the investigators will perform a randomized, single-blind, controlled feeding crossover study design (comparing Western diet to non-Western diet consumption) in young and older, exercising and non-exercising healthy adults to determine the time course effects (temporal association) of diet on the gut microbiome and arterial function. Overall, this research has potential to establish the gut microbiome as a possible target for treating/preventing age-related arterial dysfunction and reducing the risk of age-associated cardiovascular diseases.

Detailed Description

In order to investigate how age-related changes to the gut microbiome, as modulated by Western diet and exercise, influences arterial function in humans, the investigators will capitalize on the plasticity of the gut microbiome to dietary perturbations. A randomized, single-blind, 2x1-week dietary intervention crossover study (with 3 week washout) will be conducted in young (18-29 years) and old (60-79 years), exercising and non-exercising, male and female adults from all races and ethnic backgrounds. Testing will take place on the University of Colorado Boulder main campus at the Clinical and Translational Research Center (CTRC - located in the Wardenburg Health Center). Subjects will undergo telephone and in-person CTRC screening, with those eligible assigned to either Group A or Group B using block randomization stratified by age and exercise status. Group A will undergo isocaloric WD feeding (high fat \[40%\], high sugar \[25%\], low fiber \[15g\], low nutrient) during Phase 1 (first 1-week treatment period) and non-WD feeding (low-fat \[25%\], low sugar \[15%\], high fiber \[22g\], high nutrient) during Phase 2 (second 1-week treatment period). Group B will undergo the dietary interventions in the opposite order. Phases 1 and 2 will be separated by a 3-week washout period to prevent carry over effects. During each 1-week intervention period, fecal swabs will be collected daily to characterize the gut microbiome and vascular function, will be measured at baseline and after 2 and 7 days of controlled feeding to gain insight into the temporal relation between these outcomes.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
120
Inclusion Criteria
  • Age 18-29 or 60-79 years
  • Participating in < 30 min aerobic exercise < 2x/wk for >3 years OR > 45 min vigorous aerobic exercise > 4x/wk for > 3 yrs
  • Currently consuming levels of dietary fat intake with the 40th-60th percentile of Americans based on the NHANES survey (29-37% calories from fat)
  • Healthy (no clinical disease)
  • Body mass index < 30 kg/m2
  • Ankle-brachial blood pressure index > 0.9
  • Total cholesterol < 240 mg/dl
  • Fasting plasma glucose < 110 mg/dl
  • Weight stable in the past 6 months
Exclusion Criteria
  • Current or past (within 3 months of screening) use of dietary supplements, anti-inflammatory medications, drugs known to affect the gut microbiome (antibiotics, pre/probiotics, antifungals, antivirals, antiparasitics), or gastrointestinal-targeted drugs (proton pump inhibitors, H2 receptor antagonists, laxatives, antidiarrheal medications)
  • Current of past (within 5 years) smoking
  • Major change in health status in the last 6 months
  • Chronic clinical diseases (e.g., inflammatory bowl diseases, cardiovascular disease, diabetes, neurological disorders, dementia or other brain diseases of aging)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Non-Western diet firstWestern DietTo receive non-Western diet controlled feeding first, followed by Western diet controlled feeding
Western diet firstWestern DietTo receive Western diet controlled feeding first, followed by non-Western diet controlled feeding
Western diet firstNon-Western DietTo receive Western diet controlled feeding first, followed by non-Western diet controlled feeding
Non-Western diet firstNon-Western DietTo receive non-Western diet controlled feeding first, followed by Western diet controlled feeding
Primary Outcome Measures
NameTimeMethod
Change in endothelial function7 days

Brachial artery flow-mediated dilation

Change in the gut microbiome7 days

Sterile fecal swabs will be collected and analyzed using 16S rRNA sequencing

Change in arterial stiffness7 days

Carotid-femoral pulse wave velocity

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

University of Colorado Boulder

🇺🇸

Boulder, Colorado, United States

© Copyright 2025. All Rights Reserved by MedPath