(P27-034-24) Oral Contraceptive Usage Impacts Exercise-Induced Changes in the Gut Microbiota

Objectives: Oral contraceptives (OC) are the second most common contraceptive approach in the US, but their usage has been linked with increased cardiometabolic incidents. We recently showed that OC decreased physical activity and energy expenditure in mice, and this perturbation was lessened by the introduction of exercise. Exercise provides metabolic protection, partly through the modulation of the gut microbiota and energy metabolism. However, the role of the gut microbiota in exercise-related protection on OC-induced metabolic dysfunction is not known. We aim to characterize the shifts in gut microbiota in response to exercise and OC use, and relate these microbial changes with changes in energy expenditure.

Methods: Female C57BL/6J mice were provided with or without voluntary wheel running (VWR vs. Sedentary) and fed a high-fat diet with vehicle or OC (Veh vs. OC) for twelve weeks, resulting in a 2x2 factorial design. Cecal microbiota was assessed using 16S rRNA gene sequencing.

Results: While the cecal microbiota of Sedentary-OC group clustered differently (p < 0.05) than the Sedentary-Veh, substantial OC-driven taxonomic differences were not detected. To our surprise, exercise elicits a stronger impact on the gut microbiota at the community level than OC after 12 weeks of usage. Differential abundance analysis of bacterial taxa at the class level showed that VWR-Veh group had significantly (p < 0.05) greater Clostridia and significantly lower Bacilli compared to Sedentary-Veh and Sedentary-OC. At the genus level, VWR-Veh group had significantly (p < 0.05) greater Turicibacter and an uncultured genus from Lachnospiraceae compared to Sedentary-Veh and Sedentary-OC. Interestingly, VWR-OC treatment shifted these taxa to be more similar to the VWR-Veh group proportionally. Clostridia was positively associated with non-resting energy expenditure (ρ=0.37, p=0.014), total energy expenditure (ρ=0.3, p=0.042), and activity-based energy expenditure (ρ=0.38, p=0.011).

Conclusions: Our data demonstrated that 12 weeks of OC use did not drastically impact the gut microbiota. However, a significant interaction between exercise and OC on the gut microbiota was present whereby exercise-induced changes in microbial taxa associated with energy expenditure may be diminished with the use of OC.

Funding Sources: This work was partly supported by funding from the AHA and NIH.