Lactobacillus rhamnosus GG maintains gut microbiota stability and promotes intestinal adaptation via activated intestinal farnesoid X receptor signaling in short bowel syndrome

Intestinal farnesoid X receptor (FXR) signaling plays a critical role in maintaining intestinal microbiota stability. In this study, we investigated the probiotic Lactobacillus rhamnosus GG (LGG) and its ability to promote intestinal adaptation and stabilize the gut microbiota by activating intestinal FXR signaling in short bowel syndrome (SBS). In patients with type I SBS, fecal microbial α-diversity was decreased, Proteobacteria abundance was increased, and Firmicutes, Actinobacteria, and Bacteroidetes abundance levels were decreased. In vitro, LGG supernatant (LGGs) upregulated FXR expression in Caco-2 cells and ileum organoids. In vivo, LGG supplementation significantly improved intestinal morphology in wild-type (WT) SBS mice, including increased villus height, crypt depth and goblet cell numbers. Serum fibroblast growth factor 15 (FGF15) levels increased and fecal Proteobacteria abundance decreased, while secondary bile acids rose and primary bile acids declined in WT SBS mice after LGG supplementation. In addition, LGG supplementation also increased occludin and FXR expression in WT SBS mice, but not in intestinal FXR knockout (FXR^Int-KO) SBS animals. SBS disrupts FXR signaling and gut microbiota equilibrium. LGG counteracts these effects by activating intestinal FXR, which stabilizes microbiota composition, protects the mucosal barrier, and promotes intestinal adaptation both in vitro and in vivo.