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

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.

Multi-dimensional flow cytometry analysis reveals increasing changes in the systemic neutrophil compartment during seven consecutive days of endurance exercise.

Endurance exercise is associated with a transient increase in neutrophil counts in the peripheral blood. Here we investigate the impact of intensified endurance exercise on the neutrophil compartment. We hypothesized that intensified endurance exercise leads to mobilization of neutrophil subsets, which are normally absent in the blood. Furthermore, we followed the potential build-up of neutrophil activation and the impact on overnight recovery of the neutrophil compartment during a seven-day cycling tour. The neutrophil compartment was studied in 28 healthy amateur cyclists participating in an eight-day strenuous cycling tour. Blood samples were taken at baseline, after 4 days and after 7 days of cycling. The neutrophil compartment was analyzed in terms of numbers and its phenotype by deep phenotyping of flow cytometry data with the multi-dimensional analysis method FLOOD. Repeated endurance exercise led to a gradual increase in total neutrophil counts over the days leading to a 1.26 fold-increase (95%CI 1.01-1.51 p = 0.0431) in the morning of day 8. Flow cytometric measurements revealed the appearance of 2 additional neutrophil subsets: CD16brightCD62Ldim and CD16dimCD62Lbright. A complex change in neutrophil phenotypes was present characterized by decreased expression of both CD11b and CD62L and marked increased expression of LAIR-1, VLA-4 and CBRM1/5. The changes in expression were found on all neutrophils present in the blood. Strikingly, in strong contrast to our findings during acute inflammation evoked by LPS challenge, these neutrophils did not upregulate classical degranulation markers. In fact, our FLOOD analysis revealed that the exercise induced neutrophil phenotype did not overlap with the neutrophil subsets arising upon acute inflammation. In conclusion, during multiple days of endurance exercise the neutrophil compartment does not regain homeostasis overnight. Thereby our study supports the concept of a build-up of inflammatory cues during repeated endurance exercise training, causing a prolonged change of the systemic neutrophil compartment.