Folate as a Key Regulator of Animal Intestinal Homeostasis: From Metabolism to Microbiota and Barrier Function

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.