Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands.
Front Immunol. 2020 Jan 10;10:2939. doi: 10.3389/fimmu.2019.02939. eCollection 2019.
Neonatal antibiotics disturb the developing gut microbiome and are therefore thought to influence the developing immune system, but exact mechanisms and health consequences in later life still need to be elucidated. Therefore, we investigated whether neonatal antibiotics influence inflammatory markers at 1 year of age. In addition, we determined whether health problems during the first year of life, e.g., allergic disorders (eczema and wheezing) or infantile colics, were associated with changes in the circulating immune marker profile at 1 year of age. In a subgroup ( = 149) of the INCA-study, a prospective birth-cohort study, a blood sample was drawn from term born infants at 1 year of age and analyzed for 84 immune related markers using Luminex. Associations of antibiotic treatment, eczema, wheezing, and infantile colics with immune marker concentrations were investigated using a linear regression model. The trial is registered as NCT02536560. The use of broad-spectrum antibiotics in the first week of life, was significantly associated with different levels of inflammatory markers including sVCAM-1, sCD14, sCD19, sCD27, IL-1RII, sVEGF-R1, and HSP70 at 1 year of age. Eczema was associated with decreased concentrations of IFNα, IFNγ, TSLP, CXCL9, and CXCL13, but increased concentrations of CCL18 and Galectin-3. Wheezing, independent of antibiotic treatment, was positively associated to TNF-R2 and resistin. Infantile colics were positively associated to IL-31, LIGHT, YKL-40, CXCL13, sPD1, IL1RI, sIL-7Ra, Gal-1, Gal-9, and S100A8 at 1 year of age, independent of early life antibiotic treatment. In this explorative study, we identified that neonatal antibiotics are associated with immunological alterations at 1 year of age and that, independent of the antibiotic treatment, infantile colics were associated with alterations within gut associated markers. These findings support the importance of the first host microbe interaction in early life immune development.
新生儿抗生素会扰乱发育中的肠道微生物组，因此被认为会影响发育中的免疫系统，但确切的机制和对以后生活的健康后果仍需阐明。因此，我们研究了新生儿抗生素是否会影响 1 岁时的炎症标志物。此外，我们还确定了生命第一年的健康问题，如过敏症（湿疹和喘息）或婴儿绞痛，是否与 1 岁时循环免疫标志物谱的变化有关。在 INCA 研究的一个亚组（=149）中，这是一项前瞻性出生队列研究，从足月出生的婴儿中抽取 1 岁时的血液样本，并使用 Luminex 分析 84 种与免疫相关的标志物。使用线性回归模型研究抗生素治疗、湿疹、喘息和婴儿绞痛与免疫标志物浓度之间的关系。该试验在 NCT02536560 注册。 生命的第一周使用广谱抗生素与炎症标志物的不同水平显著相关，包括 sVCAM-1、sCD14、sCD19、sCD27、IL-1RII、sVEGF-R1 和 HSP70。湿疹与 IFNα、IFNγ、TSLP、CXCL9 和 CXCL13 浓度降低有关，但 CCL18 和半乳糖凝集素-3 浓度增加。喘息与 TNF-R2 和抵抗素独立于抗生素治疗呈正相关。婴儿绞痛与 IL-31、LIGHT、YKL-40、CXCL13、sPD1、IL1RI、sIL-7Ra、Gal-1、Gal-9 和 S100A8 呈正相关，与生命早期抗生素治疗无关。 在这项探索性研究中，我们发现新生儿抗生素与 1 岁时的免疫改变有关，并且独立于抗生素治疗，婴儿绞痛与肠道相关标志物的改变有关。这些发现支持了宿主与微生物早期相互作用在早期免疫发育中的重要性。
