Neonatal Antibiotic Treatment Is Associated With an Altered Circulating Immune Marker Profile at 1 Year of Age

Berthe C Oosterloo, Belinda Van't Land, Wilco de Jager, Nicole B Rutten, Margot Klöpping, Johan Garssen, Arine M Vlieger, Ruurd M van Elburg, Berthe C Oosterloo, Belinda Van't Land, Wilco de Jager, Nicole B Rutten, Margot Klöpping, Johan Garssen, Arine M Vlieger, Ruurd M van Elburg

Abstract

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.

Keywords: antibiotics; biomarkers; eczema; immune development; infant; infantile colic.

Copyright © 2020 Oosterloo, van't Land, de Jager, Rutten, Klöpping, Garssen, Vlieger and van Elburg.

Figures

Figure 1
Figure 1
(A) Hierarchical differentiating clustering, differentiating factor is Antibiotic treatment in first week of life; markers associated are sVCAM-1, sCD14, sCD19, sCD27, IL-1RII, sVEGF-R1, and HSP70. (B) Distribution of immune markers appearing in the hierarchical cluster between the children treated with antibiotics in the first week of life compared to those who were not.

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