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FRI0526 The Infantile Gut Bacterial Colonization Pattern is Associated with Higher Cytokine Responses but not to the Proportions of Putative Regulatory T Cells in Childhood
  1. A. Rudin1,
  2. R. Hardis1,
  3. S. Anna1,
  4. A. Ljung2,
  5. A.-C. Lundell1,
  6. K. Andersson1,
  7. A.E. Wold2,
  8. I. Adlerberth2
  1. 1Medicine, Rheumatology Inflammation Research
  2. 2Biomedicine, Infectious diseses, Sahlgrenska Academy, Göteborg, Sweden

Abstract

Background Establishment of the gut microbiota commences directly after birth when the neonate is exposed to microbes. The gut microbiota is a major stimulus for the immune system and late acquisition or reduced complexity of the gut flora may delay adaptive immune maturation. However, it is still unknown whether the gut bacterial colonization pattern is related to the T cell development during early childhood.

Objectives To explore whether the neonatal gut colonization pattern is related to the T cell development during the first 3 years of life.

Methods We followed 65 Swedish children prospectively from birth up to 3 years of age. Fecal samples were cultured for major facultative and anaerobic bacteria and yeasts at several time points during the first 2 months of life. The production of IL-1β, TNF, IL-6, IL-5, IL-13 and IFN-γ by mononuclear cells stimulated with PHA was analyzd at 18 and 36 months of age. Furthermore, the proportions of CD4+ T cells that were CD45RO+, FOXP3+CD25high or CTLA-4+CD25+ at birth and at 1, 4, 18 and 36 months of age were examined by flow cytometry. The relation between colonization with different groups of gut bacteria and immune parameters was analyzed with the use of multivariate factor analysis.

Results Early colonization by bifidobacteria and Escherichia coli was associated with mononuclear cells with higher capacity to produce TNF, IL-6, IL-5 and IL-13 at 18 or 36 months of age. In contrast, colonization by Staphylococcus aureus, clostridia and enterococci was inversely related to TNF, IL-5 and IL-13 responses and the proportion of CD45RO+ T cells later in childhood. There was no association between the early gut bacterial colonization pattern and the proportions of the FOXP3+CD25high and CTLA-4+CD25+ cells within the circulating CD4+ T cell population, markers of putative regulatory T cells.

Conclusions Colonization by an early gut microbiota containing bifidobacteria and Escherichia coli may enhance T cell activation in children, but does not appear to have any association with the proportions of circulating putative regulatory T cells later in life. If increased activation of the CD4+ T cells may have any relation to the development of inflammatory disordes later in childhood remains to be examined.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.5341

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