Abstract:Intestinal stem cells (ISCs) are the source of intestinal epithelial cells, maintaining intestinal homeostasis by orchestrating proliferation and differentiation. Gut microbiota and their metabolites also play a role in maintaining host intestinal homeostasis. With technological advances, the interaction between ISCs and gut microbiota has drawn increasing attention. Emerging evidence has demonstrated that ISCs regulate the composition of gut microbiota by affecting the subtypes of epithelial cells, while gut microbiota and their metabolites modulate the epithelial development mediated by ISCs. In this review, we elucidate the effects of ISCs differentiation on gut microbiota, summarize the progress in the effects of gut microbiota and their metabolites on the proliferation and differentiation of ISCs, and forecast the possible research directions in the future, aiming to give new insights into the therapies for intestinal injury.