Probiotic Lactobacillus rhamnosus GG (LGG) restores intestinal dysbacteriosis to alleviate upregulated inflammatory cytokines triggered by femoral diaphyseal fracture in adolescent rodent model

OBJECTIVE: The aim of the study was to examine the influence of femoral shaft fracture on systemic inflammation and gut microbiome in adolescent rats and evaluate the anti-inflammatory effect of Lactobacillus rhamnosus GG (LGG) and its regulation of intestinal flora, as well as illustrate the mechanism by which LGG ameliorates the inflammatory response and restores intestinal dysbacteriosis. MATERIALS AND METHODS: Twenty-four male Sprague Dawley rats of 5 to 6 weeks of age were subjected to a standard femoral shaft fracture and internally fixed with LGG supplementation in advance or on the same day of injury or with saline solution for 1 week. The levels of TNF-alpha IL-6. IL-10, and CRP were assessed using standard protocols. Furthermore, gut microbiota composition was analyzed in the fecal samples using 16S rDNA gene sequencing, and the relationship between gut microbiota variation and inflammatory response was tested. RESULTS: The serum indices of the above-mentioned inflammatory cytokines were significantly increased, and the gut microbial balance was significantly disturbed in adolescent rats by diaphyseal fractures of the femur and surgery. Moreover, L. rhamnosus strains manipulated the gut microbiota by decreasing the relative abundance of Proteobacteria and increasing that of Firmicutes, Actinobacteria and Bacteroidetes, which in turn increased the levels of IL-10 and alleviated the levels of IL-6, CRP, and TNF-alpha. CONCLUSIONS: LGG exhibited anti-inflammatory effects by alleviating the inflammatory response and regulating the gut microbiota in adolescent rats who underwent skeletal fracture and surgery. Our results suggested that the L. rhamnosus strains could be considered as an alternative dietary supplement for the prevention or treatment of skeletal injury and its associated complications.