随着全球代谢性疾病负担不断加重及人口老龄化加剧,营养学正经历从传统的“宏量营养素补给”向基于细胞信号与代谢网络的“精准营养干预”模式的重要转型[1]。在此背景下,生物活性肽(bioactive peptides, BAPs)作为一种具有明确序列结构和可编程特性的功能分子,凭借其活性多样性、高靶向性、代谢安全性与来源广泛性,成为功能食品与精准营养领域关注的焦点之一。BAPs不仅能作为氮源提供基础营养,更可充当活性物质或信号因子,在抑制关键代谢酶、调节受体信号轴通路等多个途径上展现出系统性的稳态调节能力,为慢性病的预防与干预起到了重要作用[2-3]。

据不完全统计,目前已有超10万条BAPs被报道,这些活性肽广泛分布于各类动物、植物及微生物自身蛋白、组织或其体液、分泌物中[4]。通过各类动物、细胞活性评价与代谢通路解析,发现这些BAPs在降血糖、降血脂、降血压、抗炎等方面具有重要生理功能,引发了BAPs的挖掘探索热潮。尤其随着多组学、噬菌体展示与类器官活性评价技术的融合应用与逐步推广,BAPs高通量筛选与评价策略日趋成熟,新型BAPs的挖掘探索效率得到了前所未有的提升[5]。在此背景下,各类专题、多模态BAPs数据库相继涌现,为BAPs的“数字化”驱动发展奠定了基础。依托这些海量数据,人工智能(AI)深度学习技术在BAPs活性预测、构效关系解析与序列设计中展现出巨大潜力,从预测BAPs的活性种类与强度,到其三维结构乃至蛋白折叠模型,再延伸至基于特定功能需求的肽序列设计,AI正在不断重塑BAPs的探索方式,为BAPs快速转向营养精准干预及产业应用创造新机遇[5-6]。

本文旨在系统梳理BAPs在精准营养中的研究基础与发展方向。围绕BAPs维持机体稳态的分子基础,归纳其在糖脂代谢调节、系统性抗衰老及肠道屏障修复中的关键信号靶点;同时,重点分析多肽组学、人工智能生物计算与类器官评价等技术的交叉融合,探讨BAPs在突破传统“随机挖掘、机制不清”局限、推动其由“经验筛选”向“数据驱动的理性设计”转变中的作用。希望对BAPs的“序列挖掘-结构优化-系统验证-体内响应”的全链条研发思路探讨,可为高生物学效价特医食品和精准营养制剂的开发提供理论参考与技术支撑。

1 生物活性肽的主要来源

BAPs通常主要以两种形式存在于动物、植物及微生物中[7]:游离肽——以游离形式直接存在于生命机体并直接作用于生化反应或以信号因子形式间接调节生命活动;结合肽——以肽序列形式存在于机体蛋白序列内部或与其他糖、脂分子结合存储,这类BAPs需经特定生物化学反应以进行释放,酶解即为此类BAPs的常见释放方式[8]。依据这些BAPs的探索来源,本文主要将其分为外源性活性肽与内源性活性肽[4]。

1.1 外源性活性肽

外源性活性肽是指源自于动植物、微生物等外部生物资源,经酶解、发酵或提取等技术制备,并以完整肽段形式进入人体发挥特定生理功能的活性分子。区别于传统营养素供给物质,此类肽段作为外源性信号分子或生物活性物质,在免疫调节、代谢稳态及组织修复中展现出卓越的生物学效能[7]。如乳源活性肽CPPs、GMP被报道口服后可直接增强肠道免疫,修复肠道屏障,此外,乳源性多肽IPP、VPP在小鼠灌胃吸收后,亦被证实具有较好的血压干预能力[9-10]。外源活性肽的主要来源统计结果见图1。由图1可知,在动物相关来源中,牛奶源、鱼源动物中发现的BAPs相对较多,乳蛋白在消化或酶解过程中可释放多种生物活性肽,目前在BIOPEP、MBPDB等专门数据库中,已收录并验证的乳源功能性肽数量已达数百条[5,10]。在鱼源动物中,从鳕鱼、鲑鱼及金枪鱼中分离鉴定出的多肽已被证实具有较强的自由基清除能力和血管保护作用[5]。此外,科研人员对动物中乳蛋白/肌原纤维蛋白的研究兴趣较为浓厚,故近年针对牛奶/鱼蛋白中的活性肽挖掘研究亦成为热门,业内亦有诸多企业正在开展该相关活性肽产品的开发及应用。

数字表示该来源的外源性活性肽数量。

图1 外源性活性肽的主要来源

Fig.1 Primary sources of exogenous bioactive peptides

1.2 内源性活性肽

不同于依赖体外酶解或发酵获得的外源性活性肽,内源性活性肽主要直接来源于人体及小鼠、斑马鱼等模式生物的体液与组织微环境,其序列广泛存在于血清、脑脊液、乳汁及胃肠道分泌物等生理样本中[11]。内源活性肽的主要来源统计结果见图2。由图2的来源分布特征可见,此类内源性肽段并非随机分布,而是高度集中于激素或神经肽前体蛋白(precursor proteins)库中。作为天然加工产物,它们主要通过特定的酶解级联反应释放,例如由前脑啡肽原加工生成的脑啡肽,以及血管紧张素原剪切形成的血管紧张素Ⅱ[10]。这些作为基因编码产物的天然分子,广泛富集于特定的生理体液与组织微环境中,从而展现出比外源肽更高的结构保守性与生理相关性。随着高分辨质谱及肽组学分析技术的不断发展,内源性活性肽的系统挖掘与鉴定数量持续增加,已成为食品科学与精准营养研究中的重要关注方向[5]。相关研究不断积累的人体与模式生物内源肽资源,为后续开展基于天然序列的营养干预策略设计及健康食品研发提供了可靠的数据基础与参考。

数字表示该来源的内源性活性肽数量。

图2 内源性活性肽的主要来源

Fig.2 Primary sources of endogenous bioactive peptides

2 生物活性肽的作用机制

随着BAPs研究向“机制解析”纵深发展,其通过多靶点网络维持稳态的作用日益明确[12]。生物活性肽的主要作用类别统计结果见图3。由图3可知,对炎症调节、肠胃调节及糖代谢调控等通路的研究较为热门,这反映了国内外研究人员对通过膳食干预维持“代谢稳态”的高度聚焦[13-14]。这一趋势不仅确证了BAPs作为多效功能配料的天然优势,更为其在精准营养与健康管理中的应用提供了坚实的科学支撑。

数字表示该作用类别的活性肽数量。

图3 生物活性肽主要作用类别

Fig.3 Primary action categories of bioactive peptides

2.1 调节糖脂代谢

BAPs作为食源性多效调节因子,其维持糖脂稳态的机制主要涵盖肠道界面的“信号感知”与靶组织细胞内的“转录重塑”两个关键空间维度,见图4。首先,肠道是BAPs启动代谢调节的始动环节。不同于游离氨基酸的竞争性转运,寡肽主要经由PepT1介导的质子偶联机制进入肠上皮细胞,伴随膜去极化激活电压门控钙通道(VGCCs);同时,富含芳香族残基的肽段通过CaSR 动员内质网钙库。这种“双重钙信号”直接驱动囊泡胞吐,诱导GLP-1的脉冲式分泌。如火麻仁肽 VAMP,其不仅促进GLP-1释放,更作为DPP-IV的抑制剂阻断其降解,通过强化“肠-胰轴”的信号互作改善机体代谢循环[13]。经吸收进入循环后,BAPs 通过跨膜信号转导在靶细胞内还可实现“转录重塑”,这是恢复代谢稳态的核心。针对高糖环境引发的氧化应激,鱼卵多肽FRP及山苍子肽QEGPFVR 等通过激活激酶轴(ERK1/2/PI3K),靶向结合Keap1的Kelch域并竞争性释放Nrf2。Nrf2核转位后结合ARE元件,上调抗氧化酶表达以清除线粒体ROS。这种氧化还原平衡的恢复有效遏制了SNARE 复合物的氧化失活,从而修复受损的胰岛素囊泡融合机制,恢复葡萄糖刺激的胰岛素分泌(GSIS)功能[15]。与此同时,在脂代谢调控网络中,AMPK-ACC-SREBP-1c信号轴发挥了核心枢纽作用。BAPs 激活该通路后表现出“抑合促分”的双重效应:一方面下调核转录因子SREBP-1c 及下游合成酶(FAS)表达,阻断脂质从头合成;另一方面协同上调 PPARs及CPT-1,加速线粒体脂肪酸β-氧化。例如,豌豆多肽被证实能模拟二甲双胍的作用模式,通过强效激活AMPK通路逆转异位脂质沉积,最终实现对糖脂代谢紊乱的有效干预[13]。

图4 生物活性肽介导GLP-1分泌与糖脂代谢的级联调控

Fig.4 BAPs-mediated cascade regulation of GLP-1 secretion and glucose and lipid metabolism

2.2 抗衰老

机体衰老是一个涉及基因组不稳定性、线粒体功能障碍、免疫失衡及表观遗传改变的复杂系统性过程。目前研究提示,BAPs 延缓衰老的分子机制并非单一维度的线性调控,而是涵盖了对氧化应激损伤的修复、免疫衰老的调节以及对慢性低度炎症的抑制等多个维度的网络化调控[16]。在这些复杂的交互网络中,基于“微生物-肠-脑轴”的双向通讯因其能串联起肠道稳态、代谢调节与神经保护,正成为解析BAPs实现系统性抗衰老效应的重要切入点(见图5)。具体而言,该轴线通过“肠道微环境重塑”与“神经信号传导”的双重级联通路发挥作用。一方面,在肠道侧,BAPs可发挥类益生元特性优化菌群结构,例如特异性富集 Akkermansia等有益菌以恢复微生物稳态。这种菌群优化促进了短链脂肪酸的代谢生成,进而上调肠上皮细胞中ZO-1等紧密连接蛋白的表达,修复受损的肠道物理屏障,从源头上阻断脂多糖(LPS)入血诱发的系统性“炎性衰老”[17]。另一方面,依托体液与神经传导路径,BAPs 能够远端调控脑部微环境。研究表明,活性肽可通过激活脑内Nrf2/Keap1信号轴,抑制小胶质细胞介导的神经炎症,维持线粒体功能稳态,并上调BDNF与CREB的表达[18-19]。这种对“肠道屏障-脑神经网络”的协同重塑,最终有助于增强突触可塑性与神经发生。例如核桃肽rWDP被证实兼具稳固肠屏障与激活神经元PINK1线粒体自噬的双重功效;海参多肽SCP通过上调PSD-95与BDNF 改善记忆功能;而大豆二肽GR则显示出跨越血脑屏障直接诱导皮层 BDNF 转录的潜力[20-21]。这些证据共同揭示了 BAPs 通过多维路径延缓机体功能衰退的巨大应用潜力。

图5 生物活性肽的肠-脑轴抗衰老作用机制

Fig.5 Anti-aging mechanism of bioactive peptides via gut-brain axis

2.3 肠道修复

肠道屏障的完整性是维持机体营养吸收与免疫防御的基石。图6是BAPs修复肠道屏障的作用机制,BAPs对肠道屏障的修复并非单一维度的结构填补,而是构建了一套涵盖胞内“Nupr1-自噬-线粒体”轴重塑与胞间“物理连接”加固的系统性复原方案[22]。首先,疏通自噬流构成了BAPs逆转损伤的核心策略(图6路径A)。面对氧化应激或缺血导致的自噬停滞,特定活性肽能够靶向抑制转录因子Nupr1的表达。随着Nupr1水平的下调,原本受抑的自噬流得以释放,线粒体自噬程序重启,特异性包裹并清除受损线粒体。这一机制有效阻断了ROS与mtDNA的胞内泄漏,从源头切断NLRP3炎症小体 的激活信号,进而抑制下游 NF-κB 通路及促炎因子的转录,驱动细胞从“损伤状态”向“自噬保护”表型转变[23-24]。与之并行的是,BAPs还能通过非自噬依赖路径直接强化胞间的物理屏障(图6路径B)。现有证据表明,部分结构修饰肽(如订书肽)及海洋胶原肽AVCP能够直接锚定上皮细胞膜受体,迅速激活JAK-STAT或MAPK信号级联反应。信号入核后直接促进了ZO-1与Occludin等紧密连接蛋白的基因转录,从而加速受损上皮的再上皮化与结构致密化进程[25-26]。这种“内外兼修”的双重机制,深刻揭示了 BAPs 在维持肠道稳态中的独特价值:它既能通过“自噬-炎症”轴清除胞内危险信号,又能通过上调结构蛋白重筑物理防线,为肠道损伤的精准营养干预提供了多维度的分子靶标[27]。

图6 生物活性肽修复肠道屏障的作用机制

Fig.6 Mechanism of bioactive peptides in repairing intestinal barrier

2.4 其他活性机制

除调节代谢外,BAPs在抗菌、抗肿瘤及促骨生长等领域的研究亦日益深入,特别是在血压调控、抗氧化应激及免疫调节等方面显示出确切的生物学功能。在心血管保护方面,特定大豆肽不仅能通过激活ACE2改善Ang Ⅱ诱导的内皮功能障碍,还可调控外泌体介导的miRNA传递以抑制血管炎症,从而通过改善微环境实现血压稳态调节[28]。在抗氧化与细胞保护层面,核桃源肽段可通过抑制钙超载与线粒体凋亡通路减轻神经毒性,而鲣鱼弹性蛋白肽则能通过抑制 MAPK/NF-κB 通路延缓紫外线诱导的皮肤光老化损伤[29]。这些多维度的作用机制进一步丰富了BAPs在营养学领域的科学内涵。

3 驱动活性肽精准营养干预的关键技术体系

随着精准营养的演进,BAPs研发正经历由“经验筛选”向“技术驱动”的范式升级[30]。多肽组学与AI计算的融合突破了序列挖掘与构效预测的瓶颈,而分子设计与多级生物评价的引入,则有效解决了体内稳定性与生物利用度难题[5]。这种构建“定向发现-结构优化-系统验证”的技术闭环,为活性肽在营养领域的精准应用奠定了坚实的方法学支撑。

3.1 基于多肽组学与AI生物计算的定向发现

多肽组学与人工智能技术的深度融合,正在重塑生物活性肽的发现逻辑,推动该领域从传统的“试错式筛选”向“数据驱动的理性设计”范式升级[31]。这一策略的核心在于利用高维组学数据与计算模型,旨在突破传统实验范式在筛选通量与精准度上的局限,为解析复杂的构效关系提供更理性的技术路径。首先,基于“DIA采集+AI解析”的新型质谱策略,显著拓展了复杂食品基质中内源性肽段的挖掘深度。 传统的液质联用分析(LC-MS/MS)多采用数据依赖性采集(DDA)模式,该模式在扫描时倾向于优先采集高丰度离子,往往导致部分低丰度或共洗脱的生物活性肽信息缺失。为应对这一挑战,新一代多肽组学引入了数据非依赖性采集(DIA-MS)模式,能够更为全面地捕获离子的碎片信息[32]。然而,DIA 产生的高维复杂谱图解析难度极大,这正是人工智能介入的重要切入点。通过引入深度学习算法(如光谱库预测模型),神经网络能高精度模拟肽段的碎裂规律与保留时间,从复杂的 DIA 混合谱图中“解卷积”出常规方法难以识别的微量肽段,为挖掘具有新颖骨架的活性分子奠定了翔实的物质基础[33]。其次,计算生物学平台构建了“序列-结构-功能”的集成化筛选机制,推动了活性肽的定向挖掘与从头设计。 依托 AlphaFold 等蛋白结构预测技术与分子动力学模拟(MD simulation),研究人员已能在计算机模拟(in silico)环境中完成肽段与受体蛋白的分子对接及稳定性验证,从而有效降低了对耗时的高通量湿法筛选的依赖[34]。例如,Zhou 等[35]应用该策略从大豆蛋白水解物中筛选获得 ACE2 激活肽 IVPQ 和 IAVPT。细胞实验证实,这些肽段能将血管内皮细胞的一氧化氮(NO)水平提升约 39%,并降低约 35% 的氧化应激水平(ROS),从而有效改善了内皮功能障碍。更进一步,生成式人工智能(generative AI)被应用于解析生物活性的深层构效规律,不仅能对天然肽段进行定向改造以提升其稳定性或生物利用度,更能基于特定靶点“从头生成”全新的高活性骨架[36]。这一过程有助于提升筛选的靶向性,并优化整体研发周期。生物信息学资源的整合与演进,构成了这一技术体系的数据基石。现有的数据库体系正经历从“单一序列存储”向“多维功能集成”的演变。除了BioPep、APD3等经典的序列资源库持续为基础研究提供支持外,新一代分析平台(以 PepOSX 为代表)开始整合多模态数据[37]。这类新型平台不仅集成了序列检索功能,更内嵌了AI活性预测算法与酶切模拟工具,支持了从“序列解析”到“功能预测”的全链路分析。这种数据库功能的迭代升级,使得研究者能够快速从海量组学数据中锁定高潜力的医学营养干预靶点,为后续的机制验证提供重要的理论指导[38]。常见生物活性肽数据库见表1[37,39-48]。

表1 常见生物活性肽数据库

Tab.1 Common bioactive peptide databases

数据库网址数据特征参考文献BioPephttps:∥biochemia.uwm.edu.pl/biopep-uwm常见食源性生物活性肽[39]PepOSXhttps:∥www.peposx.com集成活性肽鉴定、数据库与 AI活性预测[37]DFBPhttp:∥www.cqudfbp.net常见食源性生物活性肽[40]AHTPDBhttp:∥crdd.osdd.net/raghava/ahtpdb/index.php降血压多肽[41]SPasehttp:∥www.signalpeptide.de信号肽[42]DBAASPdbaasp.org/home抗菌活性肽及其结构特征[43]CPPsitehttp:∥crdd.osdd.net/raghava/cppsite细胞穿透肽数据库[44]THPdbhttp:∥14.139.61.8/PlantPepDB/index.php植物肽数据库[45]PlantPepDBhttp:∥crdd.osdd.net/raghava/thpdb植物肽数据库[46]Neuropephttp:∥isyslab.info/NeuroPep/browse type-organism神经肽数据库[47]APD3aps.unmc.edu/APk抗菌肽数据库[48]

3.2 基于生物工程与分子设计的定向筛选与结构优化

针对天然食源性肽稳定性不足及生物利用度低的难题,生物工程与分子设计构建了涵盖“高通量定向筛选”至“理性结构优化”的整合策略[13,49](见图7)。首先,基于噬菌体展示的高通量淘选技术实现了高亲和力序列的定向富集(图7左侧)。 相较于传统酶解分离的非定向性,该策略通过构建容量高达109级的超大肽库,并引入体外模拟胃肠液或特定受体压力进行3～5 轮亲和淘选,可将海量候选库迅速收敛至具有纳摩尔级(nmol)高亲和力的先导序列[50]。例如,Sainath等[51]利用消减淘选策略,从随机十二肽库中成功筛选出针对大肠杆菌的高活性肽 EC5;实验证实,该肽段能定向结合并破坏细菌膜结构,对大肠杆菌的最小抑菌浓度(MIC)低至 8 μg/mL,展示了该技术在从头发现高活性骨架方面的巨大优势。其次,理性分子设计旨在优化天然肽段的理化特性以适应应用环境。在获得核心序列后,为改善其消化道稳定性,研究者常结合计算机辅助设计与固相合成(SPPS)技术进行定向修饰[50]。结合图示可知,针对易被酶解的问题,可采用“订书肽”技术引入全碳侧链锁定构象,或引入非天然D-型氨基酸以降低酶的识别效率。例如,Kale等[52]利用双化学连接子辅助的噬菌体展示技术,筛选获得靶向血浆激肽释放酶的刚性双环肽。该抑制剂兼具亚纳摩尔级亲和力(Ki<1 nmol)及延长血浆半衰期(>3 d)的效果,证实了多重化学约束策略在提升肽段生物稳态方面的关键作用。此外,糖基化或脂质化修饰通过调节肽段两亲性,亦有助于增强其跨膜运输能力[49]。最后,功能导向的验证进一步明确了该技术路线的应用潜力。经结构优化的工程化肽段(如N-端修饰衍生物)在细胞及动物模型中显示出提升靶点激活效力与作用持久性的趋势。这一从“序列挖掘”到“结构重塑”的路径,为开发机制明确且具有消化稳定性的新型功能食品配料提供了理论与技术支持[53]。

图7 筛选与理性设计协同创制生物活性肽

Fig.7 Engineering screening and rational design for collaborative creation of bioactive peptides

3.3 基于多种生物模型的功能评价与机制解析

体外评价策略正经历从“二维细胞筛选”向“仿生微环境重现”的范式演进(见图8)。 鉴于传统细胞模型( Caco-2等)难以模拟组织互作,类器官与 3D 培养技术被引入以精准复刻靶组织的微环境特征。例如,Ren 等利用肠道类器官模型评估了活性肽对干细胞微环境的重塑作用。再如,Vivanco-Maroto等[54]利用小鼠空肠类器官模型,确证了溶菌酶源肽段 WIRGCRL 对 GLP-1 的诱导活性。相较于 STC-1 细胞系,该肽段在类器官中显示出更灵敏的低浓度响应特性及更高的生理相关性。正如 3D 肠道类器官模型所示,通过重构细胞外基质与干细胞分化谱系,该系统为解析营养肽在复杂生理环境下的吸收转运与抗炎机制提供了高保真平台[55]。深入机制解析层面,基因编辑技术的介入确立了活性肽作用靶点的“因果链”。相比单纯的蛋白表达量分析,利用CRISPR-Cas9系统对关键基因(如 TLR4、NLRP3)实施敲除或点突变,能够从遗传学水平严格验证BAPs调控代谢或炎症通路的必要性,将研究从相关性分析提升至机理确证的深度[23]。而在连接基础研究与营养干预的转化环节,多级动物模型提供了不可替代的体内证据。斑马鱼与啮齿类模型凭借高通量优势,广泛用于评估 BAPs 的系统性生理效应;而猪等大型动物模型则因其消化与免疫系统与人类高度相似,在评估代谢动力学及肠道修复效能方面极具参考价值,为预测 BAPs 在人体内的生物学效应与安全性提供了关键的体内证据支撑[56-58]。

图8 功能评估与机制验证的生物活性肽研究模型

Fig.8 Comprehensive research model for functional evaluation and mechanism validation of bioactive peptides

4 总结与展望

作为食品科学与现代医学的交叉枢纽,BAPs在糖脂代谢调节、衰老干预、肠稳态调节等精准营养领域展现出巨大的潜能,推动其从机理阐释向精准干预加速发展。在当前与未来,多肽组学、人工智能与生物工程的深度融合将持续推动BAPs的高效挖掘、机制解析与产业应用进展。但是,全景解析机体代谢功能因子、关键调控通路、构建高效递送体系及克服人群响应异质性,仍将是BAPs从实验室迈向应用端的核心瓶颈。未来,建立基于大数据驱动的人群分层模式,推动功能性食品由通用型补充向精准化调控转型,将是BAPs走向医学营养的关键一环,这也将为慢病的早期预防及营养调节提供有利条件。

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Advances in Functional Mechanisms of Bioactive Peptides and Precision Nutrition Intervention Technologies

Zhao Mouming1, Fan Yunxuan1, Chen Haowen1, Zhen Yiyu2, Zheng Lin1, Xiao Chuqiao3, Yu Yi4, Xu Jucai2,*

(1.School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China;2.School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China;3.School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China;4.Infinitus (China) Commodity Co., Ltd., Jiangmen 529020, China)

Abstract： Bioactive peptides (BAPs) were characterized by diverse biological activities, high target specificity, favorable metabolic safety, and a wide range of sources, and were considered important functional components driving the transition from macronutrient supplementation toward precision interventions based on cellular signaling and metabolic networks. The forms, sources, and mechanisms of action of BAPs were systematically summarized. Exogenous BAPs derived from animals, plants, and microorganisms, as well as endogenous BAPs enriched in physiological samples, including serum, cerebrospinal fluid, milk, and gastrointestinal secretions were outlined. The molecular basis underlying the roles of BAPs in glucose and lipid metabolism, anti-aging effects, and intestinal barrier repair was elucidated. BAPs were shown to regulate the gut-pancreas axis through PepT1-, CaSR-, and GLP-1-related signaling and to ameliorate oxidative stress and glucose and lipid metabolic disorders through the ERK1/2/PI3K-Nrf2 and AMPK-ACC-SREBP-1c pathways. BAPs exerted anti-aging effects by remodeling the microbiota-gut-brain axis, promoting the enrichment of beneficial microorganisms and the production of short-chain fatty acids, suppressing neuroinflammation, and maintaining mitochondrial homeostasis. In addition, BAPs inhibited inflammation and reinforced tight junctions through the Nupr1-autophagy-mitochondrial axis and the JAK-STAT and MAPK pathways. Additional functions of BAPs in blood pressure regulation, oxidative stress resistance, and immune modulation were also summarized. Furthermore, three key technological systems that facilitated BAP-based precision interventions were reviewed, including targeted discovery based on data-independent acquisition peptidomics, artificial intelligence, structural prediction, and molecular dynamics simulations; screening and structural optimization centered on phage display, solid-phase peptide synthesis, peptide stapling, and D-amino acid incorporation; and functional evaluation and mechanistic validation integrating organoids, three-dimensional culture, CRISPR-Cas9 gene editing, and multilevel animal models. On this basis, a full-chain research and development framework comprising “sequence mining-structural optimization-systematic validation-in vivo response” was proposed. Efficient delivery, elucidation of in vivo metabolic mechanisms, and interindividual variability in responses were identified as persistent barriers to translation. This review aimed to provide theoretical and technical support for the development of highly bioactive foods for special medical purposes, medical nutrition formulations, and functional foods, as well as for the early prevention of chronic diseases and precision nutritional intervention.

Keywords： bioactive peptides; precision nutrition; artificial intelligence; peptidomics; intestinal homeostasis

doi：10.12301/spxb202600028

文章编号：2095-6002(2026)04-0001-12

引用格式：赵谋明,范昀萱,陈昊文,等. 生物活性肽的作用机制及其精准营养干预技术进展[J]. 食品科学技术学报,2026,44(4):1-12.

Zhao Mouming, Fan Yunxuan, Chen Haowen, et al. Advances in functional mechanisms of bioactive peptides and precision nutrition intervention technologies[J]. Journal of Food Science and Technology, 2026,44(4):1-12.

中图分类号： TS201.4

文献标志码： A

收稿日期： 2026-01-17

基金项目： 国家自然科学基金青年科学基金项目(32402276);广东省科技创新战略专项市县科技创新支撑(大专项+任务清单)项目-暨2023年江门市关键核心技术“揭榜挂帅”制项目(2023780200060009632);广东省科协青年科技人才培育计划项目(SKXRC2025458)。

Foundation： Youth Program of the National Natural Science Foundation of China (32402276);Municipal and County Science and Technology Innovation Support Project (Major Special Program+Task List) under the Special Fund for Guangdong Provincial Science and Technology Innovation Strategy-2023 Jiangmen Key Core Technologies Project with the “Jiebang Guashuai” (2023780200060009632); Youth Science and Technology Talent Cultivation Program of Guangdong Association for Science and Technology (SKXRC2025458).

第一作者： 赵谋明,男,教授,博士,主要从事食品生物技术方面的研究。

*通信作者： 徐巨才,男,副教授,博士,主要从事多肽组学AI分析与活性肽挖掘方面的研究。E-mail: xujucai.happy@163.com。

(责任编辑：李 宁)