Neonates colonized with pathogenic bacteria in the airways have a low-grade systemic inflammation

Background and Objectives: The development of childhood asthma is associated with neonatal colonization with pathogenic bacteria in hypopharynx. Furthermore, established asthma is associated with systemic low-grade inflammation. We here report on the association between neonatal colonization with pathogenic bacteria in hypopharynx and the development of systemic low-grade inflammation. Methods: Bacterial colonization of the hypopharynx with M. catharralis, H. influenzae and/or S. pneumoniae was assessed in asymptomatic children from the Copenhagen Prospective Studies on Asthma in Childhood₂₀₀₀ (COPSAC₂₀₀₀ ) cohort at age 1 month by culturing technique (N=238) and by quantitative polymerase chain reaction (qPCR) technique (N=249) and in the COPSAC₂₀₁₀ cohort by culturing at age 1 month (N=622) and again at age 3 months (N=613). Systemic low-grade inflammation was determined in both cohorts at age 6 months by measuring plasma levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukine-6 (lL-6). Results: In both cohorts, bacterial colonization was associated with increased levels of hs-CRP: COPSAC₂₀₀₀ , 1 month culturing (geometric mean ratio of colonized/non-colonized [95% CI]), 1.39 [0.97-2.01], p=0.08, 1 month qPCR, 1.55 [1.14-2.10], p<0.01. A multi‐parametric principal component analysis incorporating hs‐CRP, TNF‐α and IL‐6 confirmed a systemic inflammatory profile in children colonized with M. catharralis, H. influenzae and/or S. pneumoniae in the hypopharynx compared to non‐colonized children (p‐values<0.05). Conclusion: The composition of the upper airway microbiome in early life may cause systemic low‐grade inflammation.