目的 探讨母亲孕晚期肠道菌群与婴儿食物过敏的关系,为微生物与食物过敏的关系提供新方向。方法 本研究为巢式病例-对照研究,选取2018年2月—2020年5月在北京大学第三医院妇产科规律产检的健康孕妇与其分娩的新生儿建立母婴队列,其中有135对母婴符合入排标准并规律随访,根据婴儿1岁以内是否出现食物过敏分为食物过敏(FA)组24对和健康对照(HC)组44对。收集母亲分娩前2周内的粪便标本以及婴儿生后5个不同时间点的粪便标本。采用16S rDNA基因测序对粪便标本进行微生物学分析。结果 FA组和HC组相比,母亲孕晚期肠道菌群在α多样性和β多样性上差异均无统计学意义(P>0.05)。HC组较FA组母亲晚期肠道菌群中霍尔德曼菌属(Z＝-2.103,P=0.035)相对丰度升高,而梭菌属ⅪⅤa群(Z＝-2.483,P=0.013)、梭菌属Ⅳ群(Z＝-2.154,P=0.031)、乳球菌属(Z＝-2.147,P=0.032)和细小单胞菌属(Z＝-2.377,P=0.017)相对丰度降低,差异均具有统计学意义。母亲孕晚期肠道菌群的主要菌属和差异菌属在婴儿肠道菌群中,在同一时间点上的差异无统计学意义(P>0.05)。结论 母亲孕晚期肠道菌群中的霍尔德曼菌属相对丰度水平为子代婴儿食物过敏的潜在预测指标,且与子代婴儿肠道菌群中该菌的相对丰度水平无关。母体肠道菌群对后代食物过敏的影响机制有待进一步研究。
Abstract
Objective To investigate the relationship between maternal intestinal microbiota in the third trimester of pregnancy and infant food allergy, so as to provide new ideas for the association between microbial and food allergy. Methods A nested case-control study was adopted. Healthy pregnant women who had regular prenatal check-ups at Peking University Third Hospital from February 2018 to May 2020 and their newborns were selected to establish a maternal and infant cohort, of whom 135 mother-infant pairs met the criteria of this study and were followed up regularly. According to whether the infants had food allergy within 1 year old, 24 pairs were divided in the food allergy (FA) group and 44 pairs in the healthy control (HC) group. Fecal samples were collected from the mothers within 2 weeks before delivery and from the infants at 5 different time points after birth. These samples were analyzed by 16S rDNA sequencing. Results There was no significant difference in α diversity and β diversity of intestinal microbiota in the third trimester of pregnancy between the FA group and the HC group (P>0.05). Compared with the FA group, the relative abundance of Holdemania in maternal intestinal flora in the HC group was significantly increased(Z＝-2.103, P=0.035), while the relative abundance of Clostridium ⅪⅤa (Z＝-2.483, P=0.013), Clostridium Ⅳ (Z＝-2.154, P=0.031), Lactococcus (Z＝-2.147, P=0.032) and Parvimonas (Z＝-2.377, P=0.017) was significantly decreased. Among the intestinal microbiota of infants, there was no statistical significance in the difference between the main microbiota and the differential microbiota of maternal intestinal microbiota in late pregnancy at the same time point (P>0.05). Conclusions The relative abundance level of Holdemania in maternal intestinal microbiota in the third trimester of pregnancy is a potential predictor of food allergy in offspring, but is not associated with the relative abundance of Holdemania in offspring intestinal microbiota. Further studies on the mechanism of maternal intestinal microbiota in late pregnancy affecting offspring food allergy are warranted.
关键词
肠道菌群 /
孕晚期 /
婴儿 /
食物过敏 /
16S rDNA测序
Key words
intestinal microbiota /
the third trimester of pregnancy /
infant /
food allergy /
16S rDNA sequencing
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参考文献
[1] Sicherer SH, Sampson HA. Food allergy[J]. J Allergy Clin Immunol, 2010,125(Suppl 2):116-125.
[2] Meyer R, Fox AT, Chebar Lozinsky A, et al. Non-IgE-mediated gastrointestinal allergies-Do they have a place in a new model of the Allergic March[J]. Pediatr Allergy Immunol,2019,30(2):149-158.
[3] Meyer R, Godwin H, Dziubak R, et al. The impact on quality of life on families of children on an elimination diet for non-immunoglobulin E mediated gastrointestinal food allergies[J]. World Allergy Organ J,2017,10(1):8.
[4] Sicherer SH, Sampson HA. Food allergy:A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management[J]. J Allergy Clin Immunol,2018,141(1):41-58.
[5] Shu SA, Yuen AWT, Woo E, et al. Microbiota and food allergy[J]. Clin Rev Allergy Immunol,2019,57(1):83-97.
[6] Iweala OI, Nagler CR. The microbiome and food allergy[J]. Annu Rev Immunol,2019,37:377-403.
[7] 屠文骆,陈先俊,徐建萍,等. 孕晚期孕妇肠道菌群对子代婴儿免疫系统发育的影响[J]. 广东医学, 2021,42(10):1207-1210.
[8] Abbring S, Engen PA, Naqib A, et al. Raw milk-induced protection against food allergic symptoms in mice is accompanied by shifts in microbial community structure[J]. Int J Mol Sci,2021,22(7):3417.
[9] Wang Y, Qian PY. Conservative fragments in bacterial 16S rRNA genes and primer design for 16S ribosomal DNA amplicons in metagenomic studies[J]. PLoS One,2009,4(10):e7401.
[10] Edgar RC. UPARSE:highly accurate OTU sequences from microbial amplicon reads[J]. Nat Methods,2013,10(10):996-998.
[11] Cole JR, Wang Q, Fish JA, et al. Ribosomal database project: data and tools for high throughput rRNA analysis[J]. Nucleic Acids Res,2014,42:633-642.
[12] Segata N, Izard J, Waldron L, et al. Metagenomic biomarker discovery and explanation[J]. Genome Biol,2011,12(6):R60.
[13] Gomez-Arango LF, Barrett HL, Wilkinson SA, et al. Low dietary fiber intake increases Collinsella abundance in the gut microbiota of overweight and obese pregnant women[J]. Gut Microbes,2018,9(3):189-201.
[14] Barrett HL, Gomez-Arango LF, Wilkinson SA, et al. A vegetarian diet is a major determinant of gut microbiota composition in early pregnancy[J]. Nutrients,2018,10(7):890.
[15] Best KP, Gold M, Kennedy D, et al. Omega-3 long-chain PUFA intake during pregnancy and allergic disease outcomes in the offspring:A systematic review and meta-analysis of observational studies and randomized controlled trials[J]. Am J Clin Nutr,2016,103(1):128-143.
[16] Chen CC, Chen KJ, Kong MS, et al. Alterations in the gut microbiotas of children with food sensitization in early life[J]. Pediatr Allergy Immunol,2016,27(3):254-262.
[17] Nylund L, Satokari R, Nikkilá J, et al. Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease[J]. BMC Microbiol,2013,13:12.
[18] Vael C, Vanheirstraeten L, Desager KN,et al. Denaturing gradient gel electrophoresis of neonatal intestinal microbiota in relation to the development of asthma[J]. BMC Microbiol,2011,11:68.
[19] Frossard CP, Steidler L, Eigenmann PA. Oral administration of an IL-10-secreting Lactococcus lactis strain prevents food-induced IgE sensitization[J]. J Allergy Clin Immunol,2007,119(4):952-959.
[20] Shin HS, Eom JE, Shin DU, et al. Preventive effects of a probiotic mixture in an ovalbumin-induced food allergy model[J]. Microbiol Biotechnol,2018,28(1):65-76.
[21] Walker RW, Clemente JC, Peter I, et al. The prenatal gut microbiome:Are we colonized with bacteria in utero?[J]. Pediatr Obes,2017,12(Suppl 1):3-17.
[22] Thum C, Cookson AL, Otter DE, et al. Can nutritional modulation of maternal intestinal microbiota influence the development of the infant gastrointestinal tract?[J]. Nutr,2012,142:1921-1928.
[23] 刘明颖,李辉,施展,等. 晚孕期孕妇口服益生菌制剂对新生儿肠道菌群及脐血IL-4、IFN-γ水平影响的临床研究[J]. 中国妇幼保健,2012,27(6):923-925.
[24] Vuillermin PJ, Macia L, Nanan R, et al. The maternal microbiome during pregnancy and allergic disease in the offspring[J]. Semin Immunopathol,2017,39(6):669-675.
[25] Tapiainen T, Paalanne N, Tejesvi MV, et al. Maternal influence on the fetal microbiome in a population-based study of the first-pass meconium[J]. Pediatr Res,2018,84(3):371-379.
[26] Ferretti P, Pasolli E, Tett A, et al. Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome[J]. Cell Host Microbe,2018,24(1):133-145.
[27] Carr LE, Virmani MD, Rosa F, et al. Role of human milk bioactives on infants' gut and immune health[J]. Front Immunol,2021,12:604080.
[28] Arpaia N, Campbell C, Fan X, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation[J]. Nature,2013,504(7480):451-455.
[29] Holder B, Jones T, Sancho Shimizu V, et al. Macrophage exosomes induce placental inflammatory cytokines: A novel mode of maternal-placental messaging[J]. Traffic,2016,17(2):168-178.
基金
国家科技重大专项课题(2017ZX09304029)
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