Influence of Short-Term Antibiotic Therapy on Exercise

Following screening, baseline evaluation, and protocol familiarization, young healthy adults will be randomly assigned to 5-days of antibiotic therapy (azithromycin) or placebo (something that has no effect). Prior to and the day after final therapy, participants will be studied during performance of treadmill exercise. Additional measurements to support data interpretation will include assessment of fecal samples to obtain insight into the gut microbiome, quantification of blood markers of inflammation and gut health, determination of body mass and composition, and quantification of daily physical activity. Azithromycin and placebo will be administered in a double-blind manner (i.e., neither the researchers nor the participants will know the identity of the placebo or the azithromycin until the study is over, and the data are analyzed).

Session 1 - Overview Participants will answer questions pertaining to health, medical history and habitual exercise. They will be assessed for body composition, and maximal oxygen uptake. Session 2 - Overview The purpose of this session is to habituate the participants to the exercise testing protocol. Habituation/familiarization with protocols decreases within-participant variability. Participants will perform standardized treadmill exercise, and then complete a performance test (time-trial).

Sessions 3 & 4 - Overview These sessions will be very similar to Session 2. Participants will perform standardized treadmill exercise and complete a performance test (time-trial). Sessions 3 and 4 will be completed prior to and one-day after 5-days of daily antibiotic therapy (azithromycin) or placebo (something that has no effect).

Session 1 - Detailed description. Session duration ~ 90 minutes. During this session participants will complete the Informed Consent, provide a brief medical history, answer questions pertaining to habitual exercise, and will undergo basic measures of body composition (height, weight, and waist and hip circumference, and density), and maximal oxygen uptake (VO2max). The medical history questionnaire will help identify contraindications to study participation. Previously it has been suggested that because of stomach upset and nausea, people receiving antibiotic therapy may lose their appetite and temporarily adjust eating behavior. Accordingly, it is also possible that over the duration of antibiotic treatment, body mass and composition may change. While not a primary outcome, body composition data will be used as an important statistical co-variable in our final analysis. The maximal exercise stress test will be used to quantify aerobic capacity and provide data such that standardized exercise may be expressed relative to maximal metabolic rate. The guidelines provided by the American College of Sports Medicine pertaining to physician supervision will be followed. During the maximal exercise test, exhaled gases will be collected in order to calculate VO2max. The VO2max measurement will characterize the endurance capacity of the participants; this is a standard and expected measurement for all human studies of endurance exercise physiology.

Session 2 - Detailed description Session duration ~ 90 minutes The purpose of this session is to habituate the participants to the exercise testing protocol. Habituation/familiarization with protocols decreases within-participant variability (i.e., the day-to-day differences between test results). Participants will perform standardized treadmill exercise, and then complete a performance test (time-trial). Standardized treadmill exercise will comprise 24-minutes of exercise: 8 minutes at 5.0 mph, 8 minutes at 6.0 mph, and 8 minutes at 7.0 mph. During this exercise heart rate will be measured and recorded. Exhaled gases will be collected in order to calculate oxygen uptake (VO2), carbon dioxide production (VCO2) and ventilation (VE). The rationale for the chosen speeds is they represent low-to-moderate intensity exercise, and they will provide three observations that will be used to determine the relationship between work rate and cardio/respiratory/metabolic responses to standardized exercise. This information will provide insight as to the physiological responses to controlled exercise and may explain and differences we may detect in un-controlled, exertion driven exercise (i.e., the time-trial). The rationale for the duration of each stage (8 minutes) is this duration is adequate for the participants to attain steady-state physiology. After a brief break (~ 5 minutes) participants will then be asked to jog/run a distance equivalent to 5-km (~3 miles) as quickly as possible, on the treadmill (i.e., a laboratory-based time-trial). Previous studies have demonstrated that practice visits help to improve time-trial performance in subsequent tests.