Abstract:The gut structure and functional performance rely on the stable type and quantity of gut mucosal epithelial cells, whose stability depends on continuous proliferation, differentiation, and migration of intestinal stem cells (ISCs) located in the crypts. Interactions between gut microbiota and ISCs support the homeostasis of the gut ecosystem. Intestinal epithelial cells (IECs) differentiated from ISCs influence the composition and function of gut microbiota through secreting immunoglobulins, mucins, etc. Meanwhile, the microorganism-associated molecular patterns (such as lipoteichoic acid and lipopolysaccharides) and metabolites (such as short-chain fatty acids and bile acids) from gut microbiota form the unique gut microenvironment to regulate the activity of ISCs and the homeostasis of IECs. Regulating the activity of ISCs and gut health by modifying gut microbiota has become a focus of current research. Thus, this review elaborates on the impact of ISCs on the gut microbiota as well as the regulatory roles of gut microbiota and related metabolites on the proliferation and differentiation fate of ISCs, aiming to broaden the understanding of the interaction between gut microbiota and ISCs. It is expected to provide strategies and targets for the regulation on gut health.