Abstract: Immunomodulatory peptides from milk (IPM) are a class of polypeptides with various biological activities such as immunomodulatory, antibacterial, and antioxidant properties. Compared to microbial fermentation, enzymatic hydrolysis offers distinct advantages including high specificity for cleavage sites, defined product structures, and superior process controllability, making it the preferred strategy for producing high-potency, standardized IPMs. This review summarizes recent advances in the enzymatic preparation of IPMs, focusing on enzyme selection strategies and the structure-activity relationship of IPMs regarding charge, hydrophobicity, and peptide chain length. Furthermore, it discusses the bidirectional mechanisms of IPMs in modulating innate and adaptive immunity, and highlights core industrial challenges such as debittering, membrane fouling control, and low oral bioavailability. Future research should integrate artificial intelligence assisted virtual screening and nano-encapsulation technologies to overcome bottlenecks in the application of IPMs.

Key words: immunomodulatory peptides; enzymatic preparation; structure-activity relationship; intestinal immunity; functional foods

摘要： 乳源免疫调节肽（immunomodulatory peptides from milk，IPM）是一类具有免疫调节、抗菌、抗氧化等多种生物活性的多肽。相比于微生物发酵法，酶法制备因其酶切位点特异性强、产物结构明确、过程可控性高成为制备高活性、标准化IPM的首选策略。本文综述近年来酶法制备IPM的关键进展，阐述酶选择策略，从电荷、疏水性及肽链长度三方面解析IPM构效关系，并探讨IPM在调节先天与适应性免疫中的双向机制，指出当前产业化面临的苦味去除、膜污染控制及口服生物利用度低等核心挑战。未来研究应结合人工智能辅助的虚拟筛选与纳米封装技术，以突破IPM的应用瓶颈。

关键词: 免疫调节肽；酶法制备；构效关系；肠道免疫；功能性食品