目的 探讨母乳来源的植物乳杆菌FN029对β-乳球蛋白(β-LG)诱导的小鼠食物过敏的缓解作用及潜在机制,为食物过敏的防治提供参考。方法 将BALB/c小鼠随机分为对照组、食物过敏组(β-LG致敏)和FN029干预组(通过灌胃给予FN029进行干预)。评估小鼠过敏症状指数;通过组织病理学染色观察肺和空肠损伤及肥大细胞浸润情况;检测血清免疫球蛋白及细胞因子水平;分析空肠Th1/Th2细胞因子mRNA表达、紧密连接蛋白表达及AKT/mTOR和NF-κB信号通路蛋白水平。结果 与对照组相比,食物过敏组小鼠出现明显的过敏症状,体重下降,脾脏指数升高;肺与空肠组织受损,肥大细胞增多;血清总IgE、β-LG特异性IgE、IgG1、组胺及IL-4水平显著升高,空肠Th2型细胞因子IL-4及Th1型细胞因子IFN-γ表达上调;肠道紧密连接蛋白(ZO-1、Occludin、Claudin-1)表达降低,AKT/mTOR及NF-κB通路关键蛋白磷酸化水平异常升高(P<0.05)。FN029干预显著改善了小鼠过敏症状和体征,减轻了组织病理损伤和肥大细胞聚集;下调了血清IgE、组胺及空肠IL-4水平,上调了IFN-γ水平,有效纠正了Th1/Th2失衡;同时,FN029促进了肠道紧密连接蛋白的恢复,并显著抑制了AKT及NF-κB的磷酸化激活(P<0.05)。结论 植物乳杆菌FN029能有效缓解小鼠食物过敏症状,其机制可能与抑制过敏原诱导的AKT/mTOR和NF-κB炎症信号通路活化、修复肠道物理屏障以及调节Th1/Th2免疫平衡有关。
Abstract
Objective To investigate the ameliorative effects and potential mechanisms of breast milk-derived Lactiplantibacillus plantarum FN029 on β-lactoglobulin (β-LG)-induced food allergy in mice, in order to provide reference for the prevention and treatment of food allergy. Methods BALB/c mice were randomly divided into a control group, a food allergy group (induced by β-LG), and an FN029 intervention group.FN029 was administered by oral gavage for intervention.Allergic symptom scores were evaluated.Histopathological staining was performed to assess lung and jejunal injury as well as mast cell infiltration.Serum immunoglobulin and cytokine levels were measured.In addition, mRNA expression of Th1/Th2 cytokines in the jejunum, expression of tight junction proteins, and protein levels of the AKT/mTOR and NF-κB signaling pathways were analyzed. Results Compared with the control group, mice in the food allergy group exhibited pronounced allergic symptoms, weight loss, and increased spleen index.Lung and jejunal tissues were damaged, with increased mast cell infiltration.Serum levels of total IgE, β-LG-specific IgE, IgG1, histamine, and IL-4 were significantly elevated, accompanied by upregulated jejunal Th2 cytokine IL-4 and Th1 cytokine IFN-γ levels.Furthermore, expression of intestinal tight junction proteins (ZO-1, Occludin, Claudin-1) was decreased, and phosphorylation levels of key proteins in the AKT/mTOR and NF-κB signaling pathways were abnormally increased (P<0.05).FN029 intervention significantly ameliorated allergic symptoms and signs, alleviated tissue damage and mast cell aggregation, downregulated serum IgE, histamine, and jejunal IL-4 levels, and upregulated IFN-γ, effectively correcting the Th1/Th2 imbalance.In addition, FN029 promoted the restoration of intestinal tight junction proteins and significantly inhibited phosphorylation activation of AKT and NF-κB (P<0.05). Conclusions Lactiplantibacillus plantarum FN029 effectively alleviates food allergy symptoms in mice, and its underlying mechanisms may be related to inhibition of allergen-induced activation of the AKT/mTOR and NF-κB inflammatory signaling pathways, restoration of the intestinal physical barrier, and modulation of Th1/Th2 immune balance.
关键词
食物过敏 /
植物乳杆菌 /
β-乳球蛋白 /
肠道屏障 /
AKT/mTOR信号通路
Key words
food allergy /
Lactiplantibacillus plantarum /
β-lactoglobulin /
intestinal barrier /
AKT/mTOR signaling pathway
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参考文献
[1] Rizzi A, Gangemi S.Food allergy: Epidemiology,pathogenesis, diagnosis, and treatment [J].J Clin Med, 2024, 13(19): 291-307.
[2] Bartha I, Almulhem N, Santos AF.Feast for thought: A comprehensive review of food allergy 2021-2023 [J].J Allergy Clin Immunol, 2024, 153(3): 576-594.
[3] Bian S, Wang R, Xu T, et al.Characteristics of cow′s milk allergy and sensitization in Chinese patients [J].Chin Med J (Engl), 2022, 135(22): 2738-2740.
[4] Ogulur I, Mitamura Y, Yazici D, et al.Type 2 immunity in allergic diseases [J].Cell Mol Immunol, 2025, 22(3): 211-242.
[5] Oettgen HC.Mast cells in food allergy: Inducing immediate reactions and shaping long-term immunity [J].J Allergy Clin Immunol, 2023, 151(1): 21-25.
[6] Haque M, Kaminsky L, Abdulqadir R, et al.Lactobacillus acidophilus inhibits the TNF-alpha-induced increase in intestinal epithelial tight junction permeability via a TLR-2 and PI3K-dependent inhibition of NF-kappaB activation [J].Front Immunol, 2024, 15: 1348010.
[7] Jiang L, Zhang L, Xia J, et al.Probiotics supplementation during pregnancy or infancy on multiple food allergies and gut microbiota: A systematic review and meta-analysis [J].Nutr Rev, 2025, 83(2): e25-e41.
[8] Hu P, Sun J, Gao R, et al.Harnessing the power of breast milk: How Lactiplantibacillus plantarum FN029 from rural western China mitigates severe atopic dermatitis in mice through retinol metabolism activation [J].Food Funct, 2025, 16(6): 2230-2246.
[9] Gong H, Li T, Liang D, et al.Milk fat globule membrane supplementation protects against β-lactoglobulininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner [J].Food Sci Hum Wellness, 2024, 13(1): 124-136.
[10] Jiang S, Hou Y, Meng L, et al.Effect of Lactiplantibacillus plantarum HM-22 on immunoregulation and intestinal microbiota in alpha-lactalbumin-induced allergic mice [J].Food Funct, 2021, 12(19): 8887-8898.
[11] Paparo L, Nocerino R, Ciaglia E, et al.Butyrate as a bioactive human milk protective component against food allergy [J].Allergy, 2020, 76(5): 1398-1415.
[12] Fu W, Zheng Z, Zhao J, et al.Allergic disease and sensitization disparity in urban and rural China: A EuroPrevall-INCO study [J].Pediatr Allergy Immunol, 2022, 33(12): e13903.
[13] Berni Canani R, Paparo L, Nocerino R, et al.Gut microbiome as target for innovative strategies against food allergy [J].Front Immunol, 2019, 10: 191.
[14] 程爽,王菊.益生菌、益生元、合生元和后生元预防与治疗牛奶蛋白过敏的研究进展 [J].中国儿童保健杂志, 2024, 32(9): 989-993.
Cheng S, Wang J.Research progress on the prevention and treatment of cow′s milk protein allergy with probiotics, prebiotics, synbiotics and postbiotics[J].Chin J Child Health Care, 2024, 32(9): 989-993.(in Chinese)
[15] Duan C, Ma L, Qin M, et al.Potential of Lactobacillus plantarum A56 in relieving food allergy through immunoregulation, antioxidation, and reshaping intestinal microbiota [J].J Nutr Biochem, 2024, 125: 109560.
[16] Pei Z, Qian L, Miao T, et al.Uncovering the mechanisms underlying the efficacy of probiotic strains in mitigating food allergies: An emphasis on gut microbiota and indoleacrylic acid [J].Front Nutr, 2024, 12(11): 1523842.
[17] Meng L, Xie H, Li Z, et al.Gut-mammary pathway: Breast milk microbiota as a mediator of maternal gut microbiota transfer to the infant gut [J].J Funct Foods, 2025, 124: 106620.
[18] Turqueti-Neves A, Otte M, Schwartz C, et al.The extracellular domains of IgG1 and T cell-derived IL-4/IL-13 are critical for the polyclonal memory IgE response in vivo [J].PLoS Biol, 2015, 13(11): e1002290.
[19] Duan C, Ma L, Yu J, et al.Oral administration of Lactobacillus plantarum JC7 alleviates OVA-induced murine food allergy through immunoregulation and restoring disordered intestinal microbiota [J].Eur J Nutr, 2023, 62(2): 685-698.
[20] Shi J, Dong P, Liu C, et al.Lactobacillus rhamnosus Probio-M9 alleviates OVA-sensitized food allergy through modulating gut microbiota and its metabolism [J].Food Funct, 2023, 14(24): 10784-10795.
[21] Poto R, Fusco W, Rinninella E, et al.The role of gut microbiota and leaky gut in the pathogenesis of food allergy [J].Nutrients, 2023, 16(1): 92.
[22] Gou HZ, Zhang YL, Ren LF, et al.How do intestinal probiotics restore the intestinal barrier? [J].Front Microbiol, 2022, 14(13): 929346.
[23] Cao LH, He HJ, Zhao YY, et al.Food allergy-induced autism-like behavior is associated with gut microbiota and brain mTOR signaling [J].J Asthma Allergy, 2022, 15: 645-664.
[24] Mohseni AH, Casolaro V, Bermudez-Humaran LG, et al.Modulation of the PI3K/Akt/mTOR signaling pathway by probiotics as a fruitful target for orchestrating the immune response [J].Gut Microbes, 2021, 13(1): 1-17.
[25] Guo Q, Jin Y, Chen X, et al.NF-κB in biology and targeted therapy: New insights and translational implications [J].Signal Transduct Target Ther, 2024, 9(1): 53.
[26] Prescott JA, Mitchell JP, Cook SJ.Inhibitory feedback control of NF-κB signalling in health and disease [J].Biochem J, 2021, 478(13): 2619-2664.
基金
江苏省重点研发计划(社会发展)项目(BE2022698);无锡市“太湖之光”科技攻关(医疗卫生)项目(Y20222003)
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