Lacticaseibacillus rhamnosus GG enhances fin regeneration under oxytetracycline exposure via activating Wnt signaling and modulating gut microbiota

Zebrafish possesses robust caudal fin regeneration which depends on multiple factors to maintain body integrity. However, it is uncertain whether the caudal fin regeneration is related to gut microbiota. Here, we investigated the effect of Lacticaseibacillus rhamnosus GG (LGG) on the regeneration of caudal fin under oxytetracycline (OTC) exposure. The results demonstrated that 1000 mu g/L OTC exposure for 4 days decreased reactive oxygen species (ROS) production at 1 and 3 h post amputation (hpa), increased neutrophil recruitment at 6 hpa, enhanced the number of apoptotic cells at 1, 3, 6 and 12 hpa and inhibited Wnt signaling pathway at 48 hpa in wound site. Furthermore, OTC exposure caused dysbacteriosis by elevating level of Proteobacteria and decreasing the abundance of Firmicutes, particularly Lacticaseibacillus, thereby negatively impacting wound healing and repair. Additionally, the administration of 106 CFU/mL of LGG for 48 h could improve intestinal environment through increasing the colonization rate of LGG in OTC-treated larvae intestines. The regenerative process restored by LGG was accompanied with increased ROS production at 1, 3 and 6 hpa, inhibited neutrophil recruitment at 6 hpa, decreased the number of apoptotic cells at 1 hpa, and activated Wnt signaling pathway at 48 hpa in OTC-treated fish. LGG is a promising bacterium for restoring fin regeneration and provides new insights regarding the correlation among the gut microbiota and fin regeneration.