Journal of Agriculture and Food Science
Journal of Agriculture and Food Science. 2026; 6: (2) ; 10.12208/j.jafs.20260013 .
总浏览量: 23
1内蒙古蒙牛乳业（集团）股份有限公司全球研发创新中心 内蒙古呼和浩特
2内蒙古乳业营养健康与安全企业重点实验室 内蒙古呼和浩特
*通讯作者： 母智深,单位：内蒙古蒙牛乳业（集团）股份有限公司全球研发创新中心 内蒙古呼和浩特; 内蒙古乳业营养健康与安全企业重点实验室 内蒙古呼和浩特; ；
炎症性肠病全球发病率持续上升，现有抗肿瘤坏死因子α（TNF-α）单抗和活菌制剂面临免疫抑制、定植困难、储存稳定性差等临床瓶颈。后生元中的益生菌表面蛋白无需活菌依赖，可直接作用于肠上皮及免疫细胞，兼具安全性与稳定性，成为新型抗炎候选物。本文系统梳理乳酸杆菌、双歧杆菌来源的S层蛋白、分子伴侣Gro-EL、粘附蛋白等表面蛋白的结构与抗炎特征，阐明TNF-α通过激活细胞外信号调节激酶1/2（ERK1/2）、核因子‑κB（NF-κB）p50/p65通路破坏紧密连接、招募白介素‑8（IL-8）/IL-6等促炎因子级联、诱导肠上皮自噬与凋亡的三重损伤机制，整合NF-κB、丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇3‑激酶/蛋白激酶B（PI3K/AKT）、Toll样受体4（TLR4）、Janus激酶/信号转导及转录激活因子（JAK/STAT）及NOD样受体家族含pyrin结构域蛋白3（NLRP3）炎症小体间的交叉调控网络。在此基础上，从物理屏障修复、信号通路抑制、免疫细胞极化和菌群稳态重塑四维度归纳表面蛋白拮抗TNF-α的作用途径。结合现有体外与动物模型证据，本文评述了该类后生元在口服递送、工程菌表面展示方面的转化前景，并指出现有研究在蛋白构效关系解析、人体临床试验验证及规模化制备工艺等方面仍存明显短板。
The global incidence of inflammatory bowel disease (IBD) keeps rising. Current anti Tumor necrosis factor‑alpha (TNF α) monoclonal antibodies and live bacterial preparations are confronted with clinical bottlenecks including immunosuppression, poor colonization and insufficient storage stability. As postbiotics, probiotic surface proteins exert effects directly on intestinal epithelial cells and immune cells independent of viable bacteria, and have emerged as novel anti inflammatory candidates owing to their favorable safety and stability profiles. This review systematically summarizes the structures and anti inflammatory properties of surface proteins derived from Lactobacillus and Bifidobacterium, including S layer proteins, molecular chaperone Gro EL and adhesion proteins. It elucidates the triple injury mechanism by which TNF α disrupts tight junctions, triggers cascades of pro inflammatory factors such as Interleukin‑8 (IL-8)/IL-6 recruitment, and induces autophagy and apoptosis of intestinal epithelium via activating the Extracellular‑signal‑regulated kinase 1/2 (ERK1/2) and Nuclear factor‑kappa B (NF-κB) p50/p65 signaling pathways. The cross regulatory network among NF-κB, Mitogen‑activated protein kinase (MAPK), Phosphatidylinositol 3‑kinase/Protein kinase B(PI3K/AKT), Toll‑like receptor 4 (TLR4), Janus kinase/Signal transducer and activator of transcription (JAK/STAT) and NOD‑like receptor family pyrin domain‑containing 3 (NLRP3) inflammasome is integrated. On this basis, the pathways whereby these surface proteins antagonize TNF-α are generalized from four dimensions: physical barrier restoration, signaling pathway inhibition, immune cell polarization and gut microbiota homeostasis remodeling. Combined with available in vitro and animal model evidence, this paper comments on the translational prospects of such postbiotics in oral delivery and surface display by engineered bacteria, and points out prominent gaps in existing research, such as the elucidation of protein structure activity relationships, human clinical trial validation and large scale preparation technologies.
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