小建中颗粒通过调节肠道菌群修复肠道屏障抑制食物过敏

张云洁, 于泳璐, 万冲, 徐宁, 肖培伦, 谢海, 刘梅芳, 徐灵芝

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重庆医科大学学报 ›› 2025, Vol. 50 ›› Issue (03) : 322-330. DOI: 10.13406/j.cnki.cyxb.003785
基础研究

小建中颗粒通过调节肠道菌群修复肠道屏障抑制食物过敏

作者信息 +

Xiaojianzhong Granule inhibits food allergy by regulating gut microbiota and repairing intestinal barrier

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History +

摘要

目的 研究小建中颗粒对食物过敏(food allergy,FA)的抑制作用,并分析肠道菌群和闭锁连接蛋白-1(zonula occluden-1,ZO-1)闭锁蛋白(Occludin)探讨相关机制。 方法 24只SPF级雌性BALB/c小鼠随机分为正常组、模型组、预防组、治疗组,每组6只。首次激发前3 d,预防组以标准剂量[5.85 g/(kg·d)]小建中颗粒灌胃,至末次激发前4 h;治疗组过敏评分后给予2倍剂量小建中颗粒3 d;其他组给予等体积蒸馏水灌胃。实验终点,行过敏评分、测肛温;流式检测肠系膜淋巴结(mesenteric lymph nodes,MLN)嗜酸性粒细胞和肥大细胞,甲苯胺蓝染色空肠组织肥大细胞,免疫组织化学法检测ZO-1、Occludin的表达;16S rRNA测序检测肠内容物菌群,高效液相色谱-质谱法分析空肠灌洗液短链脂肪酸(short-chain fatty acids,SCFAs)含量。 结果 与模型组相比,预防组和治疗组过敏评分(P=0.000,P=0.000)和肛温差下降(P=0.002,P=0.000),MLN嗜酸性粒细胞和肥大细胞比例减少(P=0.000,P=0.002;P=0.000,P=0.000),空肠肥大细胞浸润减少(P=0.000,P=0.000)。与正常组相比,模型组厚壁菌门丹毒丝菌科和苏黎世杆菌属相对丰度增加,而预防组和治疗组丹毒丝菌科和苏黎世杆菌属消失,紫单胞菌科相对丰度增加。与正常组相比,模型组空肠灌洗液丙酸盐含量减少(P=0.014),与模型组相比,预防组空肠灌洗液丙酸盐含量增加(P=0.024),治疗组明显增加(P=0.008)。模型组ZO-1表达下调(P=0.010),Occludin表达明显下调(P=0.002),而预防组和治疗组ZO-1、Occludin表达恢复正常(P=0.001,P=0.013;P=0.025,P=0.015)。 结论 小建中颗粒可改变肠道菌群组成和丰度,增加短链脂肪酸浓度,上调ZO-1Occludin的表达,促进肠道屏障修复,抑制FA。

Abstract

Objective To investigate the inhibitory effect of Xiaojianzhong Granule(XJZG) on food allergy(FA) and related mechanisms in terms of gut microbiota,zonula occluden-1(ZO-1),and Occludin. Methods A total of 24 specific pathogen-free female BALB/c mice were randomly divided into normal group,model group,prevention group,and treatment group,with 6 mice in each group. The mice in the prevention group were given XJZG by gavage at a standard dose of 5.85 g/kg/day from 3 days before the first challenge till 4 hours before the last challenge;the mice in the treatment group were given XJZG at the double dose for 3 days based on the allergy score; the mice in the other groups were given an equal volume of distilled water by gavage. At the end of the experiment,allergy score and anal temperature were measured; flow cytometry was used to measure eosinophils and mast cells in mesenteric lymph nodes(MLNs);toluidine blue staining was performed for mast cells in jejunal tissue; immunohistochemistry was used to measure the expression of ZO-1 and Occludin;16S rRNA sequencing was performed to analyze the microbiota in the intestinal content;high-performance liquid chromatography-mass spectrometry was used to measure the content of short-chain fatty acids(SCFAs) in jejunal lavage fluid. Results Compared with the model group,the prevention group and the treatment group had significant reductions in allergy score(P=0.000,P=0.000),anal temperature(P=0.002,P=0.000),the proportion of eosinophils and mast cells in MLNs(P<0.05),and mast cell infiltration in jejunal tissue(P=0.000,P=0.000). Compared with the normal group,the model group had significant increases in the relative abundances of Erysipelaceae and Turicibacter,while the prevention group and the treatment group had disappearance of Erysipelaceae and Turicibacter and an increase in the relative abundance of Porphyromonadaceae. Compared with the normal group,the model group had a significant reduction in the content of propionate in jejunal lavage fluid(P=0.014),and compared with the model group,the prevention group had a significant increase in the content of propionate in jejunal lavage fluid(P=0.024),as well as a significant increase in the treatment group(P=0.008). In the model group,the expression of ZO-1 was downregulated(P=0.010),and the expression of Occludin was significantly downregulated(P=0.002),while the expression of ZO-1 and Occludin returned to normal levels in the prevention group and the treatment group(P=0.001,P=0.013;P=0.025,P=0.015). Conclusion XJZG can change the composition and abundance of gut microbiota,increase the concentration of SCFAs,upregulate the expression of ZO-1 and Occludin,promote the repair of intestinal barrier,and inhibit food allergy.

关键词

小建中颗粒 / 食物过敏 / 肠道菌群 / 短链脂肪酸 / 闭锁连接蛋白-1

Key words

Xiaojianzhong Granule / food allergy / gut microbiota / short-chain fatty acids / zonula occluden-1

中图分类号

R392.8

引用本文

导出引用
张云洁 , 于泳璐 , 万冲 , . 小建中颗粒通过调节肠道菌群修复肠道屏障抑制食物过敏. 重庆医科大学学报. 2025, 50(03): 322-330 https://doi.org/10.13406/j.cnki.cyxb.003785
Zhang Yunjie, Yu Yonglu, Wan Chong, et al. Xiaojianzhong Granule inhibits food allergy by regulating gut microbiota and repairing intestinal barrier[J]. Journal of Chongqing Medical University. 2025, 50(03): 322-330 https://doi.org/10.13406/j.cnki.cyxb.003785

参考文献

1
Shao HM Min FF Huang MJ,et al. Novel perspective on the regulation of food allergy by probiotic:the potential of its structural components[J]. Crit Rev Food Sci Nutr202464(1):172-186.
2
Wang H Yan YQ Hung I,et al. Melatonin in food allergy:mechanism and potential therapy[J]. J Pineal Res202375(2):e12899.
3
Mendonca CE Andreae DA. Food allergy[J]. Prim Care202350(2):205-220.
4
Wood RA Togias A Sicherer SH,et al. Omalizumab for the treatment of multiple food allergies[J]. N Engl J Med2024390(10):889-899.
5
Sindher SB Hillier C Anderson B,et al. Treatment of food allergy:oral immunotherapy,biologics,and beyond[J]. Ann Allergy Asthma Immunol2023131(1):29-36.
6
申荣旻,张 妍,王 济,等. 王琦教授调体治疗过敏性疾病方法探微[J]. 北京中医药大学学报201639(1):73-76.
Shen RM Zhang Y Wang J,et al. Discussion of Professor WANG Qi’s treatment on allergic diseases by adjusting Constitution of patients[J]. J Beijing Univ Tradit Chin Med201639(1):73-76.
7
赵蔚波,王雅琦,赵海虹,等. 中医特禀(过敏)体质相关疾病及防治思路探析[J]. 中华中医药杂志202237(8):4499-4502.
Zhao WB Wang YQ Zhao HH,et al. Analysis on traditional Chinese medicine particular(allergic) constitution related diseases' prevention and treatment thinking[J]. China J Tradit Chin Med Pharm202237(8):4499-4502.
8
徐 珊,张永春,汪受传. 儿童脾虚泻106例临床发病特点分析[J]. 中医儿科杂志202117(5):29-32.
Xu S Zhang YC Wang SC. Analysis of clinical onset characteristics of 106 cases of children with diarrhea due to spleen deficiency[J]. J Pediatr Tradit Chin Med202117(5):29-32.
9
胡佳元,汤蓓,沈红卫,等. 脾胃虚寒型消化性溃疡行小建中汤治疗的临床效果[J]. 沈阳药科大学学报202138(S02):64-67.
Hu JY Tang B Shen HW,et al. The clinical efficacy of Xiaojianzhong Tang in treating digestive ulcers of the spleen and stomach deficiency-cold type[J]. J Shenyang Pharm Univ202138(S2):64-67.
10
胡蓉,李瑞. 理中汤合小建中汤加减治疗肠易激综合征疗效及对肠屏障功能、血清炎性因子和肠道菌群的影响[J]. 四川中医202341(10): 120-123.
Hu R Li R. Effect of Modified Lizhong Decoction on the treament of irritable bowel syndrome,as well as its impact on intestinal barrier function,serum inflammatory factors,and gut microbiota[J]. J Sichuan Tradit Chin Med2023,41(10):120-123.
11
张家祥,周永学,周小燕. 基于肠道微生态探讨小建中汤治疗消化性溃疡[J]. 现代中西医结合杂志202231(3):372-376.
Zhang JX Zhou YX Zhou XY. Discussion on Xiaojianzhong Decoction in treating peptic ulcer based on intestinal microecology[J]. Mod J Integr Tradit Chin West Med202231(3):372-376.
12
Zhang Y Liu JY Shao JW,et al. Effective model of food allergy in mice sensitized with ovalbumin and freud’s adjuvant[J]. Bull Exp Biol Med2021171(3):352-356.
13
Smarr CB Hsu CL Byrne AJ,et al. Antigen-fixed leukocytes tolerize Th2 responses in mouse models of allergy[J]. J Immunol2011187(10):5090-5098.
14
Zubeldia-Varela E Barker-Tejeda TC Obeso D,et al. Microbiome and allergy:new insights and perspectives[J]. J Investig Allergol Clin Immunol202232(5):327-344.
15
龙静怡,梁爱华. 中药调控肠道菌群改善溃疡性结肠炎大肠湿热证的研究进展[J]. 中国实验方剂学杂志202410(1):244-254.
Long JY Liang AH. Chinese medicine regulates intestinal flora to treat ulcerative colitis in patients with syndrome of large intestine dampness-heat:a review[J]. Chin J Exp Tradit Med Formulae202410(1):244-254.
16
Kapoor B Gulati M Gupta R,et al. Microbiota dysbiosis and myasthenia gravis:do all roads lead to Rome?[J]. Autoimmun Rev202322(5):103313.
17
Litton E Currie A Raby E,et al. Probiotics and sepsis:separating the signal from the noise[J]. Intensive Care Med202147(8):924-925.
18
Hoskinson C Dai DLY Del Bel KL,et al. Delayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease[J]. Nat Commun202314(1):4785.
19
Campbell E Hesser LA Nagler CR. B cells and the microbiota:a missing connection in food allergy[J]. Mucosal Immunol202114(1):4-13.
20
何岳珍,陈 静,史正刚,等. 脾主运化理论与肠道微生态相关性研究[J]. 中医儿科杂志202319(6):100-103.
He YZ Chen J Shi ZG,et al. Research on the correlation between the theory of “spleen governing transportation and transformation” and intestinal microecology[J]. J Pediatr Tradit Chin Med202319(6):100-103.
21
Cheng H Zhang DD Wu J,et al. Atractylodes macrocephala Koidz. volatile oil relieves acute ulcerative colitis via regulating gut microbiota and gut microbiota metabolism[J]. Front Immunol202314:1127785.
22
Hoffman JM Margolis KG. Building community in the gut:a role for mucosal serotonin[J]. Nat Rev Gastroenterol Hepatol202017(1):6-8.
23
Tan JK Macia L MacKay CR. Dietary fiber and SCFAs in the regulation of mucosal immunity[J]. J Allergy Clin Immunol2023151(2):361-370.
24
Roduit C Frei R Ferstl R,et al. High levels of butyrate and propionate in early life are associated with protection against atopy[J]. Allergy201974(4):799-809.
25
Kawano Y Edwards M Huang YM,et al. Microbiota imbalance induced by dietary sugar disrupts immune-mediated protection from metabolic syndrome[J]. Cell2022185(19):3501-3519. e20.
26
Seibert B Cáceres CJ Carnaccini S,et al. Pathobiology and dysbiosis of the respiratory and intestinal microbiota in 14 months old Golden Syrian hamsters infected with SARS-CoV-2[J]. PLoS Pathog202218(10):e1010734.
27
Kim HS Whon TW Sung H,et al. Longitudinal evaluation of fecal microbiota transplantation for ameliorating calf diarrhea and improving growth performance[J]. Nat Commun202112(1):161.
28
Tavella T Rampelli S Guidarelli G,et al. Elevated gut microbiome abundance of Christensenellaceae,Porphyromonadaceae and Rikenellaceae is associated with reduced visceral adipose tissue and healthier metabolic profile in Italian elderly[J]. Gut Microbes202113(1):1-19.
29
Gamage HKAH Tetu SG Chong RWW,et al. Fiber supplements derived from sugarcane stem,wheat dextrin and Psyllium husk have different in vitro effects on the human gut microbiota[J]. Front Microbiol20189:1618.
30
Yang LN Lin Q Han L,et al. Soy hull dietary fiber alleviates inflammation in BALB/C mice by modulating the gut microbiota and suppressing the TLR-4/NF-κB signaling pathway[J]. Food Funct202011(7):5965-5975.
31
Wang X Yu CF Liu XM,et al. Fenofibrate ameliorated systemic and retinal inflammation and modulated gut microbiota in high-fat diet-induced mice[J]. Front Cell Infect Microbiol202212:839592.
32
高小琴,徐金娣,周世康,等. 基于肠道菌群-宿主代谢相关性的大枣降低十枣汤有毒药味肠道损伤作用研究[J]. 中国中药杂志202348(10):2792-2802.
Gao XQ Xu JD Zhou SK,et al. Jujubae Fructus alleviates intestinal injury caused by toxic medicinals in Shizao Decoction based on correlation between intestinal flora and host metabolism[J]. China J Chin Mater Med202348(10):2792-2802.
33
李国峰,李咸慰,宋沁洁,等. 炙红芪对脾气虚大鼠肠道菌群组成与短链脂肪酸代谢的调节作用[J]. 中国临床药理学杂志202339(18):2669-2673.
Li GF Li XW Song QJ,et al. Regulatory effects of Hedysari Radix Preparata cum Melle on intestinal flora composition and short-chain fatty acid metabolism in rats with spleen deficiency[J]. Chin J Clin Pharmacol202339(18):2669-2673.
34
黎豫川,张远哲,杨元凤,等. 白术-木香药对脾虚腹泻型肠易激综合征大鼠肠道菌群与短链脂肪酸代谢的调节作用[J]. 中国药房202435(3):304-310.
Li YC Zhang YZ Yang YF,et al. Regulatory effects of couplet medicinals of Atractylodes macrocephala-Aucklandia lappa on gut microbiota and short-chain fatty acid metabolism in the irritable bowel syndrome rat with spleen deficiency and diarrhea[J]. China Pharm202435(3):304-310.
35
Qin WX Yu ZD Li ZC,et al. Dietary berberine and ellagic acid supplementation improve growth performance and intestinal damage by regulating the structural function of gut microbiota and SCFAs in weaned piglets[J]. Microorganisms202311(5):1254.
36
Yan SH Chang JY Hao XH,et al. Berberine regulates short-chain fatty acid metabolism and alleviates the colitis-associated colorectal tumorigenesis through remodeling intestinal flora[J]. Phytomedicine2022102:154217.
37
Kuo WT Zuo L Odenwald MA,et al. The tight junction protein ZO-1 is dispensable for barrier function but critical for effective mucosal repair[J]. Gastroenterology2021161(6):1924-1939.

基金

国家自然科学基金资助项目(81701590)
山东省高等学校“青创科技支持计划”资助项目(2021KJ106)
大学生创新创业训练计划资助项目(X2022023)

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