Nutrient sensing in intestinal stem cell: Linking dietary nutrients to cellular metabolic regulation

Diet and nutrition significantly influence health, largely by regulating intestinal nutrient absorption. The intestinal epithelium, as the primary site for nutrient uptake, undergoes continuous renewal driven by precise regulation of intestinal stem cells (ISCs). Nutrient sensing and metabolism are key determinants of ISC fate, making ISCs a central link between nutrient metabolism and the regulation of intestinal tissue renewal and homeostasis. Understanding how ISCs respond or make adaptations to nutritional signals is therefore vital for maintaining intestinal homeostasis. Recent studies have spotlighted the origin and identity of ISCs and broadened our insight into the plasticity and function of ISCs under different conditions. Mitochondria, the central hubs of energy production and metabolic signals provided by dietary components and metabolic substrates, such as glucose, amino acids, and lipids, govern the intricate balance between self-renewal and differentiation of ISCs. This review highlights the importance of nutrient sensing, metabolic regulation, and mitochondrial function in the specification of ISC fate. A thorough understanding of these mechanisms paves the way for the development of stem cell-based therapy for the mucosal healing of gastrointestinal diseases and diet intervention to foster body health.