Nutritional Control of Intestinal Stem Cells in Homeostasis and Tumorigenesis

Food and nutrition have a profound impact on organismal health and diseases, and tissue-specific adult stem cells play a crucial role in coordinating tissue maintenance by responding to dietary cues. Emerging evidence indicates that adult intestinal stem cells (ISCs) actively adjust their fate decisions in response to diets and nutritional states to drive intestinal adaptation. Here, we review the signaling mechanisms mediating the dietary responses imposed by caloric intake and nutritional composition (i.e., macronutrients and micronutrients), fasting-feeding patterns, diet-induced growth factors, and microbiota on ISCs and their relevance to the beginnings of intestinal tumors. Recent interest in dietary research and its impact on ISCs and diseases such as cancer has necessitated an integrative understanding of how diet, nutrients, and metabolism collectively regulate intestinal stemness.To date, very little has been discussed regarding how diet regulates stem cell function beyond caloric intake and energy metabolism.Our review focuses on the signaling mechanisms imposed by diverse dietary models.Crosstalk between insulin/IGF-1 and ketone body signaling constitutes a key regulatory network that modulates how dietary cues and physiological factors instruct ISC fate in intestinal homeostasis and tumorigenesis.