ObjectiveThe aim of this study was to examine the effects of probiotic supplementation on extensor digitorum longus (EDL) regeneration after grafting in mice. MethodsEDL muscles were ortho-transplanted in mice. The experimental group was given 1 × 108 colony-forming units/g body weight of Lactobacillus rhamnosus daily after EDL muscle transplantation surgeries. EDL muscle transplants were recovered after 3, 5, 7, and 14 d post-transplantation from the control as well as the experimental animals and processed for histologic analysis. ResultsAt day 3 post-transplantation, the inflammatory cells had infiltrated into the grafted EDL muscles and the central section of the grafted tissue contained necrotic fibers. At day 5 post-transplantation, the concentration of inflammatory cells increased further and degenerative muscle fibers were being replaced with centrally nucleated muscle cells. The average cross-sectional area non-grafted EDL and grafted muscle in the probiotic supplemented mice at day 7 increased to 48% and 23% (P = 0.002), respectively, compared with the respective values in the control animals. Whereas in non-grafted and grafted EDL muscle it could approach 8% and 36% (P = 0.008), respectively at 14 d compared with the corresponding values of the control EDL muscle transplants. The number of muscle fibers in the non-grafted and grafted probiotic-supplemented groups increased to12% and 20% (P = 0.045) at day 7 compared with the control EDL muscle. In non-grafted and grafted EDL muscle, the number of regenerated muscle fibers increased to 73% and 64% (P = 0.110) at day 14 compared with control EDL grafted muscle. ConclusionResults of the present study regarding better regeneration of skeletal muscle fibers in the probiotic-supplemented mice than the control grafts warrant further molecular-level investigation to understand the underlying mechanism mediating the process of skeletal muscle fiber regeneration. Probiotics possibly modulate the process of muscle fiber regeneration by adjusting the composition of gut microbiota.