肠道菌群与食物过敏的因果关联:一项孟德尔随机化分析

胡丽鑫, 范国振, 马慧, 李蕾, 王芳, 曲政海, 管仁政

中国当代儿科杂志 ›› 2025, Vol. 27 ›› Issue (4) : 444-450.

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中国当代儿科杂志 ›› 2025, Vol. 27 ›› Issue (4) : 444-450. DOI: 10.7499/j.issn.1008-8830.2409021
论著·临床研究

肠道菌群与食物过敏的因果关联:一项孟德尔随机化分析

  • 胡丽鑫, 范国振, 马慧, 李蕾, 王芳, 曲政海, 管仁政
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Causal association between gut microbiota and food allergy: a Mendelian randomization analysis

  • HU Li-Xin, FAN Guo-Zhen, MA Hui, LI Lei, WANG Fang, QU Zheng-Hai, GUAN Ren-Zheng
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摘要

目的 通过两样本孟德尔随机化(Mendelian randomization, MR)的科研方法,分析肠道菌群与食物过敏(food allergy, FA)之间的可能因果关系。 方法 使用肠道菌群和FA的全基因组关联分析数据库数据,通过MR分析,采用逆方差加权法、MR-Egger回归法、加权中位数法评估肠道菌群与FA的因果关系。采用Cochrane's Q检验评估工具变量异质性,MR-PRESSO分析测试异常值和多效性,MR-Egger回归评估水平多效性。使用“留一法”评估去除单个单核苷酸多态性后对因果关系的影响。 结果 逆方差加权法分析结果显示,疣微菌纲、疣微菌科、疣微菌目、Ruminococcaceae UCG013属和阿克曼氏菌属均与FA呈负相关(P<0.05)。敏感性分析显示结果可靠,不存在异质性和多效性。 结论 肠道菌群与FA存在因果关系,疣微菌纲、疣微菌科、疣微菌目、Ruminococcaceae UCG013属和阿克曼氏菌属可能降低FA的发病风险,为FA的治疗和预防提供了靶向调控目标,但仍需进一步研究来探究这些菌群影响FA的具体作用机制。

Abstract

Objective To analyze the potential causal relationship between gut microbiota and food allergy (FA) using two-sample Mendelian randomization (MR) methods. Methods Data from genome-wide association studies on gut microbiota and FA were utilized. MR analysis was conducted employing inverse variance weighting, MR-Egger regression, and weighted median methods to assess the causal relationship between gut microbiota and FA. Cochrane's Q test was used to evaluate heterogeneity of instrumental variables, MR-PRESSO analysis was conducted to test for outliers and pleiotropy, and MR-Egger regression was employed to assess horizontal pleiotropy. The "leave-one-out" method was used to evaluate the impact of removing individual single nucleotide polymorphisms on the causal relationship. Results Inverse variance weighting analysis revealed that the phylum Verrucomicrobia, family Verrucomicrobiaceae, order Verrucomicrobiales, genus Ruminococcaceae UCG013, and genus Akkermansia were negatively associated with FA (P<0.05). Sensitivity analyses confirmed the reliability of the findings, indicating no heterogeneity or pleiotropy present. Conclusions There is a causal relationship between gut microbiota and FA, with Verrucomicrobia, Verrucomicrobiaceae, Verrucomicrobiales, Ruminococcaceae UCG013, and Akkermansia potentially reducing the risk of developing FA. These findings provide potential targets for the treatment and prevention of FA; however, further research is needed to explore the specific mechanisms by which the microbiota influence FA.

关键词

食物过敏 / 孟德尔随机化 / 肠道菌群 / 疣微菌纲 / Ruminococcaceae UCG013 / 阿克曼氏菌属

Key words

Food allergy / Mendelian randomization / Gut microbiota / Verrucomicrobia / Ruminococcaceae UCG013 / Akkermansia

引用本文

导出引用
胡丽鑫, 范国振, 马慧, 李蕾, 王芳, 曲政海, 管仁政. 肠道菌群与食物过敏的因果关联:一项孟德尔随机化分析[J]. 中国当代儿科杂志. 2025, 27(4): 444-450 https://doi.org/10.7499/j.issn.1008-8830.2409021
HU Li-Xin, FAN Guo-Zhen, MA Hui, LI Lei, WANG Fang, QU Zheng-Hai, GUAN Ren-Zheng. Causal association between gut microbiota and food allergy: a Mendelian randomization analysis[J]. Chinese Journal of Contemporary Pediatrics. 2025, 27(4): 444-450 https://doi.org/10.7499/j.issn.1008-8830.2409021

参考文献

1 Ku?niar J, Kozubek P, Gomu?ka K. Differences in the course, diagnosis, and treatment of food allergies depending on age-comparison of children and adults[J]. Nutrients, 2024, 16(9): 1317. PMID: 38732564. PMCID: PMC11085589. DOI: 10.3390/nu16091317.
2 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. PMID: 38201921. PMCID: PMC10780391. DOI: 10.3390/nu16010092.
3 Sampath V, Abrams EM, Adlou B, et al. Food allergy across the globe[J]. J Allergy Clin Immunol, 2021, 148(6): 1347-1364. PMID: 34872649. DOI: 10.1016/j.jaci.2021.10.018.
4 Warren CM, Sehgal S, Sicherer SH, et al. Epidemiology and the growing epidemic of food allergy in children and adults across the globe[J]. Curr Allergy Asthma Rep, 2024, 24(3): 95-106. PMID: 38214821. DOI: 10.1007/s11882-023-01120-y.
5 Schettini F, Gattazzo F, Nucera S, et al. Navigating the complex relationship between human gut microbiota and breast cancer: physiopathological, prognostic and therapeutic implications[J]. Cancer Treat Rev, 2024, 130: 102816. PMID: 39182440. DOI: 10.1016/j.ctrv.2024.102816.
6 Jin Q, Ren F, Dai D, et al. The causality between intestinal flora and allergic diseases: insights from a bi-directional two-sample Mendelian randomization analysis[J]. Front Immunol, 2023, 14: 1121273. PMID: 36969260. PMCID: PMC10033526. DOI: 10.3389/fimmu.2023.1121273.
7 Li T, Wu X, Li X, et al. Cancer-associated fungi: an emerging powerful player in cancer immunotherapy[J]. Biochim Biophys Acta Rev Cancer, 2025, 17: 189287. PMID: 39971202. DOI:10.1016/j.bbcan.2025.189287
8 Singh I, Anand S, Gowda DJ, et al. Caloric restriction mimetics improve gut microbiota: a promising neurotherapeutics approach for managing age-related neurodegenerative disorders[J]. Biogerontology, 2024, 25(6): 899-922. PMID: 39177917. PMCID: PMC11486790. DOI: 10.1007/s10522-024-10128-4.
9 Yau C, Danska JS. Cracking the type 1 diabetes code: genes, microbes, immunity, and the early life environment[J]. Immunol Rev, 2024, 325(1): 23-45. PMID: 39166298. DOI: 10.1111/imr.13362.
10 Medina-Rodríguez EM, Martínez-Raga J, Sanz Y. Intestinal barrier, immunity and microbiome: partners in the depression crime[J]. Pharmacol Rev, 2024, 76(5): 956-969. PMID: 39084934. DOI: 10.1124/pharmrev.124.001202.
11 Joseph CL, Sitarik AR, Kim H, et al. Infant gut bacterial community composition and food-related manifestation of atopy in early childhood[J]. Pediatr Allergy Immunol, 2022, 33(1): e13704. PMID: 34811824. PMCID: PMC9301652. DOI: 10.1111/pai.13704.
12 Smith GD, Ebrahim S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease?[J]. Int J Epidemiol, 2003, 32(1): 1-22. PMID: 12689998. DOI: 10.1093/ije/dyg070.
13 Larsson SC, Butterworth AS, Burgess S. Mendelian randomization for cardiovascular diseases: principles and applications[J]. Eur Heart J, 2023, 44(47): 4913-4924. PMID: 37935836. PMCID: PMC10719501. DOI: 10.1093/eurheartj/ehad736.
14 van der Velde KJ, Imhann F, Charbon B, et al. MOLGENIS research: advanced bioinformatics data software for non-bioinformaticians[J]. Bioinformatics, 2019, 35(6): 1076-1078. PMID: 30165396. PMCID: PMC6419911. DOI: 10.1093/bioinformatics/bty742.
15 Kurilshikov A, Medina-Gomez C, Bacigalupe R, et al. Large-scale association analyses identify host factors influencing human gut microbiome composition[J]. Nat Genet, 2021, 53(2): 156-165. PMID: 33462485. PMCID: PMC8515199. DOI: 10.1038/s41588-020-00763-1.
16 Tu J, Wen J, Luo Q, et al. Causal relationships of metabolites with allergic diseases: a trans-ethnic Mendelian randomization study[J]. Respir Res, 2024, 25(1): 94. PMID: 38378549. PMCID: PMC10880354. DOI: 10.1186/s12931-024-02720-6.
17 Yin Y, Zhang X. The causal relationship between sleep characteristics and multi-site pain perception: a two-sample Mendelian randomization study[J]. Front Neurosci, 2024, 18: 1428951. PMID: 39193526. PMCID: PMC11347297. DOI: 10.3389/fnins.2024.1428951.
18 Zhang CY, Jiang SJ, Cao JJ, et al. Investigating the causal relationship between gut microbiota and gastroenteropancreatic neuroendocrine neoplasms: a bidirectional Mendelian randomization study[J]. Front Microbiol, 2024, 15: 1420167. PMID: 39193433. PMCID: PMC11347282. DOI: 10.3389/fmicb.2024.1420167.
19 Xilifu N, Zhang R, Dai Y, et al. Uric acid and risk of gestational diabetes mellitus: an observational study and Mendelian randomization analysis[J]. Reprod Biol Endocrinol, 2024, 22(1): 108. PMID: 39192295. PMCID: PMC11348557. DOI: 10.1186/s12958-024-01278-8.
20 Sun M, Yang H, Hu Y, et al. Differential white blood cell count and epigenetic clocks: a bidirectional Mendelian randomization study[J]. Clin Epigenetics, 2024, 16(1): 118. PMID: 39192327. PMCID: PMC11351201. DOI: 10.1186/s13148-024-01717-8.
21 Sun A, Liu S, Yin F, et al. Circulating inflammatory cytokines and sarcopenia-related traits: a Mendelian randomization analysis[J]. Front Med (Lausanne), 2024, 11: 1351376. PMID: 39193020. PMCID: PMC11347448. DOI: 10.3389/fmed.2024.1351376.
22 Zhuang X, Chen P, Yang R, et al. Mendelian randomization analysis reveals the combined effects of epigenetics and telomere biology in hematologic cancers[J]. Clin Epigenetics, 2024, 16(1): 120. PMID: 39192284. PMCID: PMC11351094. DOI: 10.1186/s13148-024-01728-5.
23 Chen X, Cai L, Fan W, et al. Causal relationships between rheumatoid arthritis and neurodegenerative diseases: a two-sample univariable and multivariable Mendelian randomization study[J]. Front Med (Lausanne), 2024, 11: 1439344. PMID: 39193017. PMCID: PMC11347450. DOI: 10.3389/fmed.2024.1439344.
24 Davis EC, Monaco CL, Insel R, et al. Gut microbiome in the first 1000 days and risk for childhood food allergy[J]. Ann Allergy Asthma Immunol, 2024, 133(3): 252-261. PMID: 38494114. PMCID: PMC11344696. DOI: 10.1016/j.anai.2024.03.010.
25 Zhang Q, Cheng L, Wang J, et al. Antibiotic-induced gut microbiota dysbiosis damages the intestinal barrier, increasing food allergy in adult mice[J]. Nutrients, 2021, 13(10): 3315. PMID: 34684316. PMCID: PMC8539551. DOI: 10.3390/nu13103315.
26 Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions?[J]. Nat Rev Immunol, 2021, 21(11): 739-751. PMID: 33846604. DOI: 10.1038/s41577-021-00538-7.
27 Perkin MR, Strachan DP. The hygiene hypothesis for allergy: conception and evolution[J]. Front Allergy, 2022, 3: 1051368. PMID: 36506644. PMCID: PMC9731379. DOI: 10.3389/falgy.2022.1051368.
28 Feng J, Ma H, Huang Y, et al. Ruminococcaceae_UCG-013 promotes obesity resistance in mice[J]. Biomedicines, 2022, 10(12): 3272. PMID: 36552029. PMCID: PMC9776008. DOI: 10.3390/biomedicines10123272.
29 Chinthrajah RS, Hernandez JD, Boyd SD, et al. Molecular and cellular mechanisms of food allergy and food tolerance[J]. J Allergy Clin Immunol, 2016, 137(4): 984-997. PMID: 27059726. PMCID: PMC5030841. DOI: 10.1016/j.jaci.2016.02.004.
30 Bae M, Cassilly CD, Liu X, et al. Akkermansia muciniphila phospholipid induces homeostatic immune responses[J]. Nature, 2022, 608(7921): 168-173. PMID: 35896748. PMCID: PMC9328018. DOI: 10.1038/s41586-022-04985-7.
31 Cani PD, Depommier C, Derrien M, et al. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms[J]. Nat Rev Gastroenterol Hepatol, 2022, 19(10): 625-637. PMID: 35641786. DOI: 10.1038/s41575-022-00631-9.

基金

国家自然科学基金项目(82300389);山东省医药卫生科技发展计划项目(202212070731)。

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