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Background Gut microbiota and intestinal inflammation regulate the development of immune-mediated diseases, such as allergies. Fecal calprotectin is a biomarker of intestinal inflammation. Objective We evaluated the association of early-age fecal calprotectin levels to the later development of allergic diseases in children from farming and non-farming environments and further studied the effect of gut microbiota on the fecal calprotectin levels. Methods Fecal calprotectin was measured from 758 infants participating in the PASTURE study at the age of 2 months using the ELISA method. Serum-specific IgE levels were measured at 6 years of age. Data of environmental factors, doctor-diagnosed atopic dermatitis ( AD) and asthma were collected by questionnaire. Multivariate logistic regression models were used for analysis. The composition of fecal microbiota was analysed in a subgroup of 120 infants with 16S rRNA pyrosequencing. The effect of Escherichia coli lipopolysaccharide ( LPS) on in vitro monocyte IL-10 secretion was studied by flow cytometry. Results The infants with high fecal calprotectin levels at 2 months, that is above the 90th percentile, had an increased risk of developing AD and asthma/asthmatic bronchitis by the age of 6 years ( aOR 2.02 (1.06-3.85) and 2.41 (1.25-4.64), respectively). High fecal calprotectin levels correlated negatively with fecal Escherichia. LPS from E. coli stimulated production of IL-10 in monocytes. Conclusion and Clinical Relevance High degree intestinal inflammation at 2 months of age, detected as high fecal calprotectin, predicted asthma and AD by the age of 6 years and was linked to low abundance of fecal Escherichia. Impaired IL-10 activation due to the lack of colonization with E. coli could explain the intestinal inflammation associated high fecal calprotectin and later risk of asthma and AD. Our results have implications for the design of probiotic treatments and suggest that early intestinal colonization has long-term health effects. [ABSTRACT FROM AUTHOR]

It has been suggested that intestinal microbiota of allergic and non-allergic children differs in composition, and that microbiota–immune system interactions may predispose children to develop sensitization. Previous studies have examined fecal microbiota of allergic children with atopic dermatitis, but little is known about that of atopic wheezy children. To investigate the composition of the fecal microbiota of young sensitized wheezy and non-sensitized non-wheezy children, using molecular methods. Within the context of a prospective birth cohort, we carried out a nested case–control study of sensitized wheezy children (cases) and non-sensitized non-wheezy controls. Cases and controls were matched for age, sex, parental atopy, allergen exposure, and pet ownership. We evaluated the composition of fecal microbiota by nucleic acid-based methods (PCR combined with denaturing gradient gel electrophoresis and quantification of bifidobacteria by fluorescent in situ hybridization). Thirty-three case–control pairs (mean age 4.4 years) provided stool samples. Comparison of total bacterial community profiles showed that each child had a unique fecal microbiota (mean Dice's similarity coefficient 22%, range 3.3–60.8%). There was no difference between the groups in prevalence of Lactic Acid bacteria (12/33 vs. 11/33, P=0.8) or bifidobacteria (30/33 vs. 31/33, P=1.00, cases vs. controls). The bifidobacterial species detected were similar in both groups. The percentage of bifidobacteria in total fecal microflora was no different between cases (median 1.7%, range 0–20.8%) and controls (1.9%, 0–18.2%, P=0.7). However, cases with eczema had significantly fewer bifidobacteria (median 1.6%, range 0–4.8%) than their controls (4.0%, 1.9–18.2%, P=0.05). We found no differences in fecal microbiota composition between sensitized wheezy and non-sensitized, non-wheezy children aged 3–5 years using nucleic acid-based methods. Differences appear to be isolated to those allergic children with eczema. [ABSTRACT FROM AUTHOR]