Special Milk and Synthetic Biology: A Dual-Perspective Review of Ingredient Substitutions in Breast-Milk-Simulated Infant Formula.

Breast milk (BM) serves as the gold standard for infant nutrition, yet conventional cow's milk-based infant formulas (IF) fail to adequately replicate its structural and functional complexity. This review critically examines two complementary paradigms, specialty milk utilization and synthetic biology-enabled precision manufacturing, as transformative strategies for developing biomimetic IF ingredients. Specialty milks, including goat milk, camel milk, donkey milk, buffalo milk, and yak milk, exhibit compositional proximity to BM in specific dimensions, including digestibility, sn-2 fatty acid profiles, and fat globule size distribution. Synthetic biology platforms have achieved notable industrial-scale successes, particularly in producing 2'-fucosyllactose and recombinant lactoferrin. However, significant knowledge gaps persist: the reconstruction of complex multi-site phosphorylation, the high-fidelity assembly of triple-layer milk fat globule membranes, and cost-effective large-scale production remain unresolved challenges. Critically, most studies focus on single components rather than integrated formula systems, and robust clinical validation is lacking. This review argues that the convergence of specialty milk matrices with precision-fermented bioactives represents a paradigm shift from compositional to structure-function biomimicry. Priority research areas include multi-omics-based integration strategies, harmonized regulatory frameworks, and well-designed clinical trials to establish functional equivalence. Addressing these gaps will be essential for developing next-generation IF that more closely emulates the functional complexity of BM.