Postoperative exercise modulating gut microbiota and associated metabolites to facilitate bone-tendon healing in rotator cuff tears

BACKGROUND: Rotator cuff tear is a prevalent shoulder injury, and postoperative exercise is considered to facilitate healing. However, the effect of postoperative exercise on rotator cuff tear healing through gut microbiota and metabolites remains unclear. METHODS: The control (con) group (n = 10) underwent sham surgeries, while the model (mod) and postoperative exercise (sport) groups (each n = 10) underwent supraspinatus tendon repair surgeries. Starting on postoperative day 7, the sport group underwent treadmill exercise at 10 m/min for 20 min/day, 5 days/week, for 4 consecutive weeks. Subsequently, the supraspinatus tendon-humerus complex, fecal, and serum samples were collected. RESULTS: Synchrotron radiation micro-CT and histological studies indicated that postoperative exercise was associated with reduced bone loss and enhanced new bone formation at tendon-bone sites. Gut microbiome profiling revealed that exercise was associated with reshaped microbial composition, with increased Proteobacteria and Dubosiella, and decreased Lachnoclostridium and Allobaculum in the sport group compared with the model group. Functional analyses showed that the HIF-1 signaling pathway and β-Alanine metabolism were notably enriched following exercise. Network correlation analysis suggested that Dubosiella functioned as a central taxon within the microbial community. Metabolomics suggested that exercise was associated with altered metabolite abundances like Val-Pro-Asp-Pro-Arg, which correlated with pathways like gap junction. Moreover, metabolomics further identified β-Alanine metabolism as the key overlapping pathway connecting microbial alterations with serum metabolic changes, with β-alanyl-L-arginine as a representative metabolite. Seven microbe-metabolite pairs showed significant correlations. Among them, Parabacteroides exhibited strong associations with multiple metabolites, including cycloheptyl derivatives, and demonstrated predictive value for tendon-bone healing (AUC = 0.88). CONCLUSION: In a murine model, postoperative exercise following rotator cuff tear repair surgery was associated with modulating gut microbiota and metabolites, which may contribute to rotator cuff tear healing. This finding provides preclinical insights into integrating postoperative exercise into rotator cuff tear recovery strategies.