Background: 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. Methods: In a subgroup (N = 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. Results: 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. Conclusion: 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.

中文翻译：

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新生儿抗生素治疗与 1 岁时循环免疫标志物谱的改变有关。

背景：新生儿抗生素会扰乱正在发育的肠道微生物群，因此被认为会影响正在发育的免疫系统，但确切的机制和对以后生活的健康影响仍需阐明。因此，我们研究了新生儿抗生素是否影响 1 岁时的炎症标志物。此外，我们还确定了出生第一年的健康问题，例如过敏性疾病（湿疹和喘息）或婴儿绞痛，是否与一岁时循环免疫标记物谱的变化有关。方法：在 INCA 研究（一项前瞻性出生队列研究）的一个亚组（N = 149）中，从 1 岁足月出生的婴儿中抽取血液样本，并使用 Luminex 分析 84 种免疫相关标记物。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记物浓度的关联。该试验注册号为NCT02536560。结果：出生后第一周使用广谱抗生素与出生后 1 年的不同水平炎症标志物（包括 sVCAM-1、sCD14、sCD19、sCD27、IL-1RII、sVEGF-R1 和 HSP70）显着相关。年龄。湿疹与 IFNα、IFNγ、TSLP、CXCL9 和 CXCL13 浓度降低相关，但与 CCL18 和 Galectin-3 浓度升高相关。喘息与抗生素治疗无关，与 TNF-R2 和抵抗素呈正相关。1 岁时，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，与早期抗生素治疗无关。结论：在这项探索性研究中，我们发现新生儿抗生素与 1 岁时的免疫学改变有关，并且独立于抗生素治疗，婴儿绞痛与肠道相关标记物的改变有关。这些发现支持了首次宿主微生物相互作用在生命早期免疫发育中的重要性。