Associations Between the Microbiome, Skeletal Muscle Perfusion, and Fitness Status
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Oral Nitrate Reducing Capacity
研究概览
简要总结
The purpose of the study is to determine associations between fitness status, bacteria in the mouth, and the blood flow to muscle. This study is trying to find out if fitness status impacts the bacteria that are present in the oral microbiome (environment in the mouth) or the ability of the body to send blood to the skeletal muscle.
Participants will complete all or some of the following:
- A mouth swab to assess the bacteria in their mouths.
- Produce a saliva sample into a tube.
- Cycle on a bike until you reach maximum effort.
- Undergo blood draws
- Wear a 24-hour non-invasive device that monitors blood pressure.
- Drink 70mL (1/3 of a cup) of concentrated beetroot juice once
详细描述
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Nitric oxide (NO) is a gaseous diatomic free-radical and is essential for a plethora of physiological functions involved in cardiometabolic health and CVD risk. NO bioavailability is associated with greater tissue perfusion, mitochondrial function, glucose regulation, and overall reduced CVD risk. The primary source of circulating NO is vascular endothelial nitric oxide synthase.
Unfortunately, the endothelium can be disrupted/damaged via a variety of CVD risk factors such as hypertension, smoking, hyperlipidemia, diabetes, inflammation, and hypercholesteremia. Disruption of the vascular endothelium and loss of bioavailable NO is a preliminary step in the progression of atherosclerosis and CVD. Decreased NO bioavailability and vascular dysfunction have been shown in a variety of clinical conditions including patients heart failure and peripheral artery disease (PAD).
Recently, an exogenous approach to increasing NO bioavailability via oral supplementation of inorganic nitrate (NO3-) has been utilized to increase NO bioavailability in various healthy and clinical populations. Briefly, inorganic NO3- is swallowed, absorbed into the circulation, and sequestered back into the salivary glands. NO3- is then secreted into the oral cavity, where bacteria containing nitrate reductase enzymes convert NO3- to nitrite (NO2-), which is again swallowed and absorbed into the circulation. NO2- in the plasma is then easily reduced to NO via non-enzymatic reactions.
This study aims to better elucidate the relationship between the oral microbiome abundance and diversity and NO3- to NO2- to NO conversion across a variety of subject populations ranging from healthy subjects to those with risk factors for CVD and people with diagnosed CVD. We also aim to examine the relationship between oral microbiome NO3- reduction and impaired skeletal muscle perfusion and exercise capacity as NO bioavailability plays a large role in these physiological processes.
The results of this study may allow us to better understand how novel interventions to modify the oral microbiome may improve cardiometabolic health and physical function in individuals with CVD and outline potential new therapeutic approaches.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- •Subjects may be of either sex with age 18 years.
排除标准
- •Oral antibiotic use within previous four weeks
- •Oral disease or poor oral health as determined by the Oral Health Questionnaire
- •Using an antibacterial mouthwash or a mouthwash containing chlorhexidine and unwilling to discontinue use
- •Tobacco smokers
- •Pregnant or lactating females
- •Hypersensitivity to any ultrasound contrast agent
- •Inability to perform exercise
- •Unable to communicate effectively in English to the study team.
- •Diagnosis of chronic renal failure (GFR < 60 ml/min/1.73m)
- •Subjects taking nitroglycerine (or inorganic nitrates), PDE-5 inhibitors (ex: Cialis, Viagra), and xanthine oxidase inhibitors (ex: Allopurinol).
结局指标
主要结局
Oral Nitrate Reducing Capacity
时间窗: Baseline, 4-weeks, 12-weeks, 6-months
Assessment of the oral microbiome's ability to reduce nitrate to nitrite. This will be measured through a swab on the dorsal surface of the tongue, an unstimulated saliva sample, and a rinse of a standard nitrate solution.
次要结局
- Aerobic Capacity(Baseline, 4-weeks, 12-weeks, 6-months)
研究者
Jason Allen
Professor of Kinesiology
University of Virginia