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

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.

• Western Diet (Other): high fat (40%), high sugar (25%) and low fiber (15g/day)
• Non-Western Diet (Other): low fat (25%), low sugar (15%), high fiber (30g/day)

Primary outcomes

• Change in the gut microbiome [7 days]: Sterile fecal swabs will be collected and analyzed using 16S rRNA sequencing
• Change in endothelial function [7 days]: Brachial artery flow-mediated dilation
• Change in arterial stiffness [7 days]: Carotid-femoral pulse wave velocity

Sex: All, ages: 18 Years to 79 Years, accepts healthy volunteers

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)

• Douglas R Seals, PhD, Principal investigator, University of Colorado, Boulder