Intestinal microbiota and its effect on the immune system--a nested case-cohort study on prevention of atopy among small children in Trondheim: the IMPACT study.

BACKGROUND

In the past 20-30 years, the prevalence of atopic diseases, particularly among children in the Western world, has increased. It has been suggested that Western lifestyle may have reduced the overall exposure to microbial stimulation early in life. The role of the gut flora in this connection has been studied, but prospective studies are in demand. Within the frame of a comprehensive controlled prospective primary prevention study of atopy and allergic diseases with the aim to reduce the incidence of atopy and allergic diseases among children from birth to six years, a nested case-cohort study is established, "The IMPACT study".

AIM

The aim of "The IMPACT study" is to study the impact of gut microbiota composition on cytokine profile development, and on development of atopic disease.

DESIGN

Information on risk factors and on disease, together with biological specimens, will be collected prospectively, and analysed in a nested case-cohort design.

METHOD

720 pregnant women are recruited from the control-cohort in the PACT study. The composition of the infant gut microbiota is analysed in stool samples from all children with atopic disease, and randomly selected children sensitized and not sensitized at age 2, at 4, 7, 10 days after birth, and at age 4, 12 and 24 months. 16S rDNA hybridisation technique will be used to specify and quantify the microbial composition in faeces. Cord blood from the same children and venous blood at age 10 days, 4, 12 and 24 months are collected to study the cytokine profile at different ages, in relation to microbial stimulation. Peripheral blood mononuclear cells (PBMC) are stored in liquid nitrogen, and faeces are stored at -80 degrees C. Atopic children will be identified by questionnaire, and the diagnosis confirmed by paediatric examination at age 2 years.