Gut Microbiota Derived Hyocholic Acid Enhances Type 3 Immunity and Protects Against Salmonella enterica serovar Typhimurium in Neonatal Rats

The gut microbiome plays a crucial role in the development of intestinal immunity in early life, but the underlying mechanisms remain largely unknown. Thus, we aimed to elucidate how microbiome colonization promotes the development of intestinal type 3 immunity in early life. Our findings show that a hypoxic environment in the intestine promotes colonization by the microbiome, particularly Lactobacillus species, early in life. HCA produced by Lactobacillus suppresses FXR signaling and enhances Rorc stability through the FXR WTAP m6A axis, which leads to type 3 gama-delta T cell and ILC3 expansion and increased resistance to S. Typhimurium infection of the intestine.