INTESTINAL MICROFLORA AND IMMUNITY

Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study

John Penders¹, Carel Thijs², Piet A van den Brandt¹, Ischa Kummeling¹, Bianca Snijders¹, Foekje Stelma⁴, Hanne Adams⁴, Ronald van Ree³, Ellen E Stobberingh⁴

¹ Department of Epidemiology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, the Netherlands
² Department of Epidemiology, Care and Public Health Research Institute (Caphri), Maastricht University, Maastricht, the Netherlands
³ Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands
⁴ Department of Medical Microbiology, University Hospital of Maastricht, Maastricht, the Netherlands

Correspondence to:
John Penders
Department of Epidemiology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, PO Box 616, 6200 MD Maastricht, the Netherlands; j.penders{at}epid.unimaas.nl

Background and aims: Perturbations in intestinal microbiota composition due to lifestyle changes may be involved in the development of atopic diseases. We examined gut microbiota composition in early infancy and the subsequent development of atopic manifestations and sensitisation.

Methods: The faeces of 957 infants aged 1 month and participating in the KOALA Birth Cohort Study were analysed using quantitative real-time PCR. Information on atopic symptoms (eczema, wheeze) and potential confounders was acquired through repeated questionnaires. Total and specific IgE were measured in venous blood samples collected during home visits when the infant was 2 years old. During these home visits a clinical diagnosis of atopic dermatitis was made according to the UK-Working Party criteria.

Results: The presence of Escherichia coli was associated with a higher risk of developing eczema (OR_adj = 1.87; 95% CI 1.15 to 3.04), this risk being increased with increasing numbers of E coli (p_{for trend} = 0.016). Infants colonised with Clostridium difficile were at higher risk of developing eczema (OR_adj = 1.40; 95% CI 1.02 to 1.91), recurrent wheeze (OR_adj = 1.75; 95% CI 1.09 to 2.80) and allergic sensitisation (OR_adj = 1.54; 95% CI 1.02 to 2.31). Furthermore, the presence of C difficile was also associated with a higher risk of a diagnosis of atopic dermatitis during the home visit (OR_adj = 1.73; 95% CI 1.08 to 2.78).

Conclusion: This study demonstrates that differences in gut microbiota composition precede the development of atopy. Since E coli was only associated with eczema and C difficile was associated with all atopic outcomes, the underlying mechanisms explaining these association may be different.

Abbreviations: CFU, colony forming units; Ig, immunoglobulin; IL, interleukin; OR, odds ratio; Th1, Th2, T helper 1, 2; Treg, regulatory T cell; UK-WP, UK-Working Party

Keywords: atopy; Clostridium difficile; Escherichia coli; gut microbiota; infant

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