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生命最初 3 年的母乳喂养与循环免疫标志物:DIABIMMUNE 研究。

Breastfeeding and circulating immunological markers during the first 3 years of life: the DIABIMMUNE study.

机构信息

Department of Public Health and Welfare, Health and Well-Being Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.

Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

出版信息

Diabetologia. 2022 Feb;65(2):329-335. doi: 10.1007/s00125-021-05612-2. Epub 2021 Nov 27.

Abstract

AIMS/HYPOTHESIS: Our aim was to study the association between duration of breastfeeding and circulating immunological markers during the first 3 years of life in children with HLA-conferred susceptibility to type 1 diabetes.

METHODS

We performed a longitudinal analysis of 38 circulating immunological markers (cytokines, chemokines and growth factors) in serum samples from Finnish (56 individuals, 147 samples), Estonian (56 individuals 148 samples) and Russian Karelian children (62 individuals, 149 samples) at 3, 6, 12, 18, 24 and 36 months of age. We also analysed gut inflammation markers (calprotectin and human β defensin-2) at 3 (n = 96) and 6 months (n = 153) of age. Comparisons of immunological marker medians were performed between children who were breastfed for 6 months or longer vs children who were breastfed for less than 6 months.

RESULTS

Breastfeeding for 6 months or longer vs less than 6 months was associated with lower median of serum immunological markers at 6 months (granulocyte-macrophage colony-stimulating factor [GMCSF], macrophage inflammatory protein [MIP-3α]), 12 months (IFN-α2, vascular endothelial growth factor, GMCSF, IFN-γ, IL-21), 18 months (FGF-2, IFN-α2) and 24 months of age (CCL11 [eotaxin], monocyte chemoattractant protein-1, TGFα, soluble CD40 ligand, IL-13, IL-21, IL-5, MIP-1α) (all p < 0.01) but not at 36 months of age. Breastfeeding was not associated with gut inflammation markers at 3 and 6 months of age.

CONCLUSIONS/INTERPRETATION: Children who were breastfed for 6 months or longer had lower medians for 14 immunological markers at one or more age points during the first 2 years of life compared with children who were breastfed for less than 6 months. The clinical meaning of the findings is not clear. However, the present study contributes to the understanding of immunological differences in children that have been breastfed longer, and thus provides a mechanistic suggestion for the previously observed associations between breastfeeding and risk of type 1 diabetes.

摘要

目的/假设:我们的目的是研究在具有 1 型糖尿病 HLA 易感性的儿童中,母乳喂养持续时间与生命最初 3 年循环免疫标志物之间的关系。

方法

我们对芬兰(56 人,147 份样本)、爱沙尼亚(56 人,148 份样本)和俄罗斯卡累利阿儿童(62 人,149 份样本)的 38 种循环免疫标志物(细胞因子、趋化因子和生长因子)血清样本进行了纵向分析,这些样本在 3、6、12、18、24 和 36 个月时采集。我们还在 3 个月(n=96)和 6 个月(n=153)时分析了肠道炎症标志物(钙卫蛋白和人β防御素-2)。比较了母乳喂养 6 个月或更长时间的儿童与母乳喂养不足 6 个月的儿童的免疫标志物中位数。

结果

与母乳喂养不足 6 个月相比,母乳喂养 6 个月或更长时间与 6 个月(粒细胞-巨噬细胞集落刺激因子[GMCSF]、巨噬细胞炎症蛋白[MIP-3α])、12 个月(IFN-α2、血管内皮生长因子、GMCSF、IFN-γ、IL-21)、18 个月(FGF-2、IFN-α2)和 24 个月(CCL11[嗜酸性粒细胞趋化因子]、单核细胞趋化蛋白-1、TGFα、可溶性 CD40 配体、IL-13、IL-21、IL-5、MIP-1α)的血清免疫标志物中位数较低(均 p<0.01),但在 36 个月时则不然。母乳喂养与 3 个月和 6 个月时的肠道炎症标志物无关。

结论/解释:与母乳喂养不足 6 个月的儿童相比,在生命最初 2 年内的一个或多个时间点,母乳喂养 6 个月或更长时间的儿童有 14 种免疫标志物中位数较低。研究结果的临床意义尚不清楚。然而,本研究有助于了解母乳喂养时间较长的儿童的免疫差异,并为之前观察到的母乳喂养与 1 型糖尿病风险之间的关系提供了一种机制上的解释。

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Early-life factors contributing to type 1 diabetes.导致 1 型糖尿病的早期生活因素。
Diabetologia. 2019 Oct;62(10):1823-1834. doi: 10.1007/s00125-019-4942-x. Epub 2019 Aug 27.
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The Importance of Human Milk for Immunity in Preterm Infants.人乳对早产儿免疫的重要性。
Clin Perinatol. 2017 Mar;44(1):23-47. doi: 10.1016/j.clp.2016.11.008. Epub 2016 Dec 27.
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Comparison of the different kinds of feeding on the level of fecal calprotectin.不同喂养方式对粪便钙卫蛋白水平的比较。
Early Hum Dev. 2014 Sep;90(9):471-5. doi: 10.1016/j.earlhumdev.2014.06.005. Epub 2014 Jul 12.

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