Abstract
Intestinal homeostasis disorders (IHDs), driven by food safety issues, pollution, and drug-resistant pathogens, threaten global health. Key factors in intestinal and metabolic diseases (like IBD, obesity, and liver disease) include barrier dysfunction, gut microbiota imbalance, and excessive immune activation. Transcription factors in intestinal epithelial cells are crucial regulators. ELF4, an ETS family transcription factor, plays vital roles in transcriptional regulation, impacting tumorigenesis, the DNA damage response, and the cell cycle. ELF4 deficiency exacerbates alcoholic liver disease (ALD). Significantly, ELF4 is a novel IFN-I transcription factor with antiviral capabilities. Its regulation of the type I IFN response offers new avenues for developing antiviral and anticancer strategies and managing IFN-induced autoimmune disorders. Thus, ELF4 emerges as a promising target for preventing and treating IHD-related diseases. Mechanistic studies could help identify diets or antimicrobials that activate intestinal ELF4 to combat pathogen/virus-induced intestinal diseases.