目的 探讨不同喂养方式对牛奶蛋白过敏(CMPA)患儿肠道菌群的影响,以期为临床合理选用肠道微生态治疗CMPA患儿提供理论指导。 方法 收集2020年9月— 2021年10月于遵义医科大学附属医院就诊 CMPA 患儿(24例)和健康婴儿(26例)的粪便,提取粪便细菌DNA,对16S rDNA V3-V4区进行PCR扩增,并在高通量测序后进行细菌学分类,从 Beta多样性、Alpha多样性、物种组成分析、物种差异分析4个方面,分析不同喂养方式 CMPA 患儿肠道菌群的多样性及结构差异。 结果 母乳喂养的CMPA患儿肠道菌群多样性高于母乳喂养的健康婴儿(P＜0.05),混合喂养的CMPA患儿与混合喂养的健康婴儿、人工喂养的CMPA患儿与人工喂养的健康婴儿相比,肠道菌群多样性差异无统计学意义(P>0.05),显著差异菌为:母乳喂养的CMPA患儿双歧杆菌属、大肠杆菌-志贺氏菌属显著富集,混合喂养的CMPA患儿链球菌属、罗氏菌属显著富集,人工喂养的CMPA患儿未分类的肠杆菌属、枸橼酸杆菌属显著富集。 结论 不同喂养方式CMPA婴儿存在肠道菌群紊乱,该结果可能为不同喂养方式CMPA的发病机制研究及其微生态干预提供部分理论依据。
Abstract
Objective To explore the effects of various feeding methods on the gut microbiota of infants with cow's milk protein allergy (CMPA), in order to provide theoretical guidance for the rational selection of intestinal microecological treatment for infants with CMPA. Methods Fecal samples of 24 infants with CMPA and 26 healthy infants were collected from September 2020 to October 2021 in the Affiliated Hospital of Zunyi Medical University. Bacterial DNA was extracted from these samples, followed by PCR amplification of the V3-V4 region of the 16S rDNA. High-throughput sequencing was then conducted for bacterial classification. The structure and diversity of intestinal flora of CMPA infants with different feeding methods were analyzed from four aspects: beta diversity analysis, alpha diversity analysis, species composition analysis and species difference analysis. Results Infants with CMPA who were exclusively breastfed exhibited greater gut microbiota diversity compared to healthy breastfed infants (P<0.05). Conversely, there was no significant difference in intestinal microflora diversity between mixed-fed CMPA infants and mixed-fed healthy infants, formula-fed CMPA infants and formula-fed healthy infants(P＞0.05). Notable distinctions included enriched populations of Bifidobacterium and Escherichia-Shigella in breastfed CMPA infants, Streptococcus and Rothia in mixed-fed CMPA infants, and unclassified Enterobacteriaceae and Citrobacter in formula-fed CMPA infants. Conclusion Intestinal flora disorder exists in infants with different feeding patterns of CMPA, which may provide some theoretical basis for the study of pathogenesis and microecological intervention of CMPA with different feeding patterns.
关键词
牛奶蛋白过敏 /
肠道菌群 /
喂养方式 /
高通量测序 /
婴儿
Key words
cow's milk protein allergy /
intestinal microbiota /
feeding pattern /
high-throughput sequencing /
infants
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参考文献
[1] Schoemaker AA, Sprikkelman AB, Grimshaw KE, et al. Incidence and natural history of challenge-proven cow's milk allergy in European children--EuroPrevall birth cohort[J]. Allergy, 2015, 70(8):963-972.
[2] Nwaru BI, Hickstein L, Panesar SS, et al. Prevalence of common food allergies in Europe: A systematic review and meta-analysis[J]. Allergy, 2014, 69(8):992-1007.
[3] Yang M, Tan M, Wu J, et al. Prevalence, characteristics, and outcome of cow's milk protein allergy in Chinese infants: A population-based survey[J]. J Parenter Enteral Nutr, 2019, 43(6):803-808.
[4] 陈同辛,洪莉,王华,等. 中国婴儿轻中度非IgE介导的牛奶蛋白过敏诊断和营养干预指南[J]. 中华实用儿科临床杂志,2022,37(4):241-250.
Chen TX, Hong L, Wang H, et al. Guidelines for the diagnosis and nutritional intervention of mild to moderate non-IgE-mediated cow's milk protein allergy in Chinese infants[J]. Chinese Journal of Applied Clinical Pediatrics, 2022, 37(4): 241-250.(in Chinese)
[5] Kayama H, Okumura R, Takeda K. Interaction Between the Microbiota, Epithelia, and Immune Cells in the Intestine[J]. Annu Rev Immunol, 2020, 38:23-48.
[6] Tilg H, Zmora N, Adolph TE, et al. The intestinal microbiota fuelling metabolic inflammation[J]. Nat Rev Immunol, 2020, 20(1):40-54.
[7] Song SJ, Dominguez-Bello MG, Knight R. How delivery mode and feeding can shape the bacterial community in the infant gut[J]. CMAJ, 2013, 185(5):373-374.
[8] Fan W, Huo G, Li X, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in infants during the six months of life[J]. J Microbiol Biotechnol, 2014, 24(2):133-143.
[9] 王晶,黄丽英,陆俊佳,等.基于16S rRNA基因测序分析不同喂养方式对食物过敏婴幼儿肠道微生态的影响[J].重庆医学,2021,50(24):4218-4222.
Wang J, Huang LY, Lu JJ, et al. Analysis of the impact of different feeding methods on the gut microbiota of infants with food allergies based on 16S rRNA gene sequencing[J]. Chongqing Medicine, 2021, 50(24): 4218-4222.(in Chinese)
[10] Wang S, Wei Y, Liu L, et al. Association between breastmilk microbiota and food allergy in infants[J]. Front Cell Infect Microbiol, 2021, 11:770913.
[11] Sicherer SH, Sampson HA. Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment[J]. J Allergy Clin Immunol, 2014, 133(2):291-307..
[12] Lyons KE, Ryan CA, Dempsey EM, et al. Breast milk, a source of beneficial microbes and associated benefits for infant health[J]. Nutrients, 2020,12(4):1039.
[13] van Odijk J, Kull I, Borres MP, et al. Breastfeeding and allergic disease: A multidisciplinary review of the literature (1966-2001) on the mode of early feeding in infancy and its impact on later atopic manifestations[J]. Allergy, 2003, 58(9):833-843.
[14] Mennini M, Arasi S, Fiocchi AG. Allergy prevention through breastfeeding[J]. Curr Opin Allergy Clin Immunol, 2021, 21(2):216-221.
[15] Mennini M, Reddel S, Del Chierico F, et al. Gut microbiota profile in children with IgE-mediated cow's milk allergy and cow's milk sensitization and probiotic intestinal persistence evaluation[J]. Int J Mol Sci, 2021,22(4):1649.
[16] Park YM, Lee SY, Kang MJ, et al. Imbalance of gut streptococcus, clostridium, and akkermansia determines the natural course of atopic dermatitis in infant[J]. Allergy Asthma Immunol Res, 2020, 12(2):322-337.
[17] Tun HM, Peng Y, Chen B, et al. Ethnicity associations with food sensitization are mediated by gut microbiota development in the first year of life[J]. Gastroenterology, 2021, 161(1):94-106.
[18] Zimmermann P, Messina N, Mohn WW, et al. Association between the intestinal microbiota and allergic sensitization, eczema, and asthma: A systematic review[J]. J Allergy Clin Immunol, 2019, 143(2):467-485.
[19] Liu R, Peng C, Jing D, et al. Biomarkers of gut microbiota in chronic spontaneous urticaria and symptomatic dermographism[J]. Front Cell Infect Microbiol, 2021, 11:703126.
[20] Kataoka H, Mori T, Into T. Citrobacter koseri stimulates dendritic cells to induce IL-33 expression via abundant ATP production[J]. J Med Microbiol, 2021, 70(3):001303.
[21] Matsui S, Kataoka H, Tanaka JI, et al. Dysregulation of intestinal microbiota elicited by food allergy induces iga-mediated oral dysbiosis[J]. Infect Immun, 2019, 88(1):e00741-19.
[22] Xiao Y, Zhai Q, Zhang H, et al. Gut colonization mechanisms of lactobacillus and bifidobacterium: An argument for personalized designs[J]. Annu Rev Food Sci Technol, 2021, 12:213-233.
[23] Hol J, van Leer EH, Elink Schuurman BE, et al. The acquisition of tolerance toward cow's milk through probiotic supplementation: A randomized, controlled trial[J]. J Allergy Clin Immunol, 2008, 121(6):1448-1454.
[24] Jing W, Liu Q, Wang W. Bifidobacterium bifidum TMC3115 ameliorates milk protein allergy in by affecting gut microbiota: A randomized double-blind control trial[J]. J Food Biochem, 2021, 45(11):e13591.
[25] Li N, Yu Y, Chen X, et al. Bifidobacterium breve M-16V alters the gut microbiota to alleviate OVA-induced food allergy through IL-33/ST2 signal pathway[J]. J Cell Physiol, 2020, 235(12):9464-9473.
基金
遵义医学院附属医院博士科研启动基金合同书[院字(2014)01号];遵义市科技局联合基金[遵市科合HZ字(2020)244号];遵义市科技局联合基金[遵市科合HZ字(2022)363号]; 贵州省科技计划项目(黔科合基础-ZK[2024]312号)
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