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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 signalingmechanismsmediating 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.