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Neonatal Antibiotic Treatment Is Associated With an Altered Circulating Immune Marker Profile at 1 Year of Age
Berthe C Oosterloo1, Belinda Van't Land2,3, Wilco de Jager2
1Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Insights
Neonatal antibiotics alter immune markers by age one. Early life health issues like infantile colics also show distinct immune profiles, highlighting the importance of early microbial interactions for immune development.
Area of Science:
- Pediatrics
- Immunology
- Microbiome Research
Background:
- Neonatal antibiotic exposure may impact immune system development.
- Mechanisms and long-term health consequences of early antibiotic use require further investigation.
- Early life health conditions may correlate with immune marker profiles.
Purpose of the Study:
- To investigate the influence of neonatal antibiotics on inflammatory markers at one year of age.
- To determine associations between early life health problems (eczema, wheezing, colic) and immune marker profiles at one year.
- To elucidate the role of early host-microbe interactions in immune development.
Main Methods:
- Prospective birth-cohort study (INCA-study) involving 149 infants.
- Blood samples analyzed for 84 immune markers using Luminex at one year of age.
- Linear regression models used to assess associations between antibiotic treatment, health conditions, and immune markers.
Main Results:
- Broad-spectrum neonatal antibiotics correlated with altered levels of inflammatory markers (e.g., sVCAM-1, sCD14, IL-1RII).
- Eczema associated with altered levels of IFNα, IFNγ, TSLP, CXCL9, CXCL13, CCL18, and Galectin-3.
- Wheezing linked to TNF-R2 and resistin; infantile colics linked to gut-associated markers (e.g., IL-31, CXCL13, S100A8), independent of antibiotics.
Conclusions:
- Neonatal antibiotics are associated with immunological alterations by one year of age.
- Infantile colics show distinct immune marker profiles, independent of early antibiotic exposure.
- Findings underscore the critical role of early host-microbe interactions in immune system maturation.
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.
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