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

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

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.

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.

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)