Division of Allergy and Immunology and Center for Food Allergy, Department of Pediatrics, University of Rochester School of Medicine and Dentistry and Golisano Children's Hospital, Rochester, NY, United States.
Department of Microbiology and Immunology and Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States.
Front Immunol. 2021 Oct 11;12:741513. doi: 10.3389/fimmu.2021.741513. eCollection 2021.
BACKGROUND: In addition to farming exposures in childhood, maternal farming exposures provide strong protection against allergic disease in their children; however, the effect of farming lifestyle on human milk (HM) composition is unknown. OBJECTIVE: This study aims to characterize the maternal immune effects of Old Order Mennonite (OOM) traditional farming lifestyle when compared with Rochester (ROC) families at higher risk for asthma and allergic diseases using HM as a proxy. METHODS: HM samples collected at median 2 months of lactation from 52 OOM and 29 ROC mothers were assayed for IgA and IgA antibodies, cytokines, endotoxin, HM oligosaccharides (HMOs), and targeted fatty acid (FA) metabolites. Development of early childhood atopic diseases in children by 3 years of age was assessed. In addition to group comparisons, systems level network analysis was performed to identify communities of multiple HM factors in ROC and OOM lifestyle. RESULTS: HM contains IgA and IgA antibodies broadly recognizing food, inhalant, and bacterial antigens. OOM HM has significantly higher levels of IgA to peanut, ovalbumin, dust mites, and as well TGF-β2, and IFN-λ3. A strong correlation occurred between maternal antibiotic use and levels of several HMOs. Path-based analysis of HMOs shows lower activity in the path involving lactoneohexaose (LNH) in the OOM as well as higher levels of lacto--neotetraose (LNnT) and two long-chain FAs C-18OH (stearic acid) and C-23OH (tricosanoic acid) compared with Rochester HM. OOM and Rochester milk formed five different clusters, e.g., butyrate production was associated with , , and cluster. Development of atopic disease in early childhood was more common in Rochester and associated with lower levels of total IgA, IgA to dust mite, as well as of TSLP. CONCLUSION: Traditional, agrarian lifestyle, and antibiotic use are strong regulators of maternally derived immune and metabolic factors, which may have downstream implications for postnatal developmental programming of infant's gut microbiome and immune system.
背景:除了儿童时期的农耕暴露,母亲的农耕暴露也能为其子女提供对过敏性疾病的强大保护;然而,农耕生活方式对人乳(HM)成分的影响尚不清楚。
目的:本研究旨在通过将 HM 作为替代物,比较传统的旧秩序门诺派(OOM)农耕生活方式的母体免疫效应与罗切斯特(ROC)高哮喘和过敏性疾病风险家庭,以特征化母体免疫效应。
方法:从 52 名 OOM 和 29 名 ROC 母亲的中位 2 个月哺乳期采集 HM 样本,检测 IgA 和 IgA 抗体、细胞因子、内毒素、HM 低聚糖(HMOs)和靶向脂肪酸(FA)代谢物。评估儿童在 3 岁时是否患有早期儿童特应性疾病。除了组间比较外,还进行了系统水平的网络分析,以确定 ROC 和 OOM 生活方式中多个 HM 因素的社区。
结果:HM 含有广泛识别食物、吸入物和细菌抗原的 IgA 和 IgA 抗体。OOM HM 对花生、卵清蛋白、尘螨和 TGF-β2 以及 IFN-λ3 的 IgA 水平显著较高。母体使用抗生素与几种 HMO 水平之间存在很强的相关性。基于 HMO 的路径分析表明,在 OOM 中涉及内酯六糖(LNH)的路径活性较低,以及乳--新四糖(LNnT)和两种长链 FA C-18OH(硬脂酸)和 C-23OH(二十三烷酸)水平较高。与罗切斯特 HM 相比,OOM 和罗切斯特奶形成了五个不同的簇,例如,丁酸的产生与 、 和 簇有关。在罗切斯特,儿童早期特应性疾病的发展更为常见,与总 IgA、尘螨 IgA 以及 TSLP 水平较低有关。
结论:传统的、农业的生活方式和抗生素的使用是母体来源的免疫和代谢因素的强大调节剂,这可能对婴儿肠道微生物组和免疫系统的产后发育编程有下游影响。
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