(P19-025-25) Gut Microbiota Depletion Increases Metabolic Activity After Fracture in Mice

Objectives: Bone fractures are increasingly common traumatic events. The effects of fracture extend beyond the injured bone; recent evidence suggests it may impact the microbiome, a key regulator of metabolism. However, the role of microbiota in modulating post-fracture metabolism is unknown. This study explores how microbiota depletion affects metabolic and ambulatory outcomes after fracture in mice.

Methods: Female 5-month-old C57BL/6J mice (n=5/group) were randomly assigned to control (CON) or microbiota depletion (Abx) groups. Depletion was attained via a broad-spectrum antibiotic cocktail. Baseline measures were collected prior to closed unilateral mid-diaphyseal femoral fracture. The Oxymax/CLAMS system recorded metabolic (VO₂, VCO₂, RER), activity, and wheel running (RUN) for two weeks post-fracture. Negative binomial regression and mixed-effects models assessed differences, using weight and time as covariates.

Results: After fracture, body mass and fat declined before improving in both groups. Day seven fasting blood glucose was lower in Abx (p=0.03). Baseline VO₂ and VCO₂ were higher in Abx (p < 0.0001). Group × time interactions were observed for VO₂ (p < 0.0001) and was higher in CON on days 3-9 and in Abx on days 11-15. VCO₂ was higher in Abx for most timepoints (p < 0.01), and RER was higher in Abx on all days (p < 0.001). Baseline y-axis activity and RUN were higher in CON (p < 0.05). Post-fracture, CON showed more x- and z-axis activity (p < 0.0001), and Abx exhibited more y-axis activity (p < 0.0001). The RUN was higher in Abx on post-fracture days 1-7 but in CON on days 8-14 (p < 0.0001).

Conclusions: Microbiota depletion alters post-fracture metabolism and activity in mice. Elevated RER and VCO₂ suggest increased carbohydrate oxidation and metabolic activity in Abx. Values for VO₂ showed an inverse relationship with RUN. VO₂ was lower when RUN was elevated in Abx, and higher when RUN was reduced in Abx. Increased z-axis activity in CON indicates more rearing behavior. Temporal RUN changes highlight activity differences between groups. These findings highlight the role of the gut microbiota in post-fracture metabolism and activity patterns, informing gut microbiota-targeted nutritional strategies for optimal recovery.

Funding Sources: Funded by Arizona State University and US Department of Veterans Affairs.