Folate is a central nutrient in one-carbon metabolism, contributing to nucleotide biosynthesis, methionine cycling, methyl-donor supply, and epigenetic regulation. In animals, the intestine is both a principal site of folate absorption and a key target organ for folate action. This narrative review focuses primarily on livestock, poultry, aquaculture species, ruminants, and animal-source food enrichment, while also using rodent, human, and in vitro studies as mechanistic or translational evidence. We synthesize evidence on folate absorption, transport, and metabolism and evaluate the mechanisms through which folate influences intestinal health. Available evidence suggests that adequate folate supply may support epithelial renewal, tight-junction integrity, mucosal immune balance, antioxidant capacity, gut microbiota stability, short-chain fatty acid production, and epigenetic regulation of intestinal development. These effects have been reported in poultry, pigs, fish, ruminants, rodents, and maternal–offspring models. However, the evidence is uneven across species, and dose–response relationships, folate forms, bioavailability, and species-specific requirements remain major limitations for translating current knowledge into animal production. Future studies should compare folic acid, 5-methyltetrahydrofolate, natural reduced folates, microbiota-derived folate, and folate-producing probiotics; quantify the contribution of microbiota-derived folate to host methyl-donor pools; and develop precision strategies that integrate folate with other one-carbon nutrients, probiotics, and product-enrichment technologies.

Objectives: Iron deficiency impairs intestinal mucosal structure and function, yet its impact on intestinal stem cells (ISCs) remains unclear. This study was therefore designed to examine how iron deficiency affects the proliferation and differentiation of ISCs. Methods: Iron-deficient mouse and enteroid models were established. Expression of key cell markers was analyzed using Western blot, qPCR, and immunofluorescence. Results: Iron deficiency led to structural impairment of the intestinal mucosa, characterized by decreased small intestinal villus height. In iron-deficient mice, expression of ChrA (enteroendocrine cell marker), Lyz (Paneth cell marker), and Muc2 (goblet cell marker) was significantly downregulated across duodenum, jejunum and ileum, whereas Vil1 (enterocyte marker) expression increased. Moreover, both Lgr5 (an ISC marker) expression and the number of Ki67-positive proliferating cells were significantly reduced, along with a decrease in Ki67 transcriptional levels under iron-deficient conditions. Similarly, deferoxamine (DFO)-treated enteroids showed fewer Lgr5-positive ISCs, downregulation of Lgr5, Lyz and Muc2, and upregulation of Vil1. RNA-seq further confirmed that iron deficiency skews ISC differentiation toward absorptive lineage. This shift was associated with modulation of the Notch signaling pathway: upregulation of the ligand Dll1, receptors Notch2 and Notch3, and the protease ADAM10, alongside downregulation of the negative regulator Atoh1. These findings indicate that Notch pathway activation promotes enterocyte differentiation under iron deprivation. Conclusions: Iron deficiency suppressed the proliferation of ISCs and induced their differentiation toward enterocytes, which is associated with the modulation of the Notch signaling pathway, providing a mechanistic insights for impaired intestinal repair and the potential for nutrient-targeted therapies.