title: High level of fecal calprotectin at age 2 months as a marker of intestinal inflammation predicts atopic dermatitis and asthma by age 6.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland.|Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Orivuori
authors.affiliation: Environmental Health Department, National Institute for Health and Welfare, Kuopio, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Mustonen
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: de Goffau
authors.affiliation: Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Hakala
authors.affiliation: Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Paasela
authors.affiliation: Christine Kühne - Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.|Children's Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Roduit
authors.affiliation: The Department of Respiratory Disease, Université de Franche-Comté, UMR-CNRS Chrono-Environnement, University Hospital, Besançon, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Dalphin
authors.affiliation: Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Genuneit
authors.affiliation: Christine Kühne - Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.|Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Lauener
authors.affiliation: Children and Young Adults' Medicine, Children's Hospital, Schwarzach, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Riedler
authors.affiliation: Dr. von Hauner Children's Hospital of the Ludwig Maximilian University Munich, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Weber
authors.affiliation: Dr. von Hauner Children's Hospital of the Ludwig Maximilian University Munich, Munich, Germany.|Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Mölndal, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: von Mutius
authors.affiliation: Environmental Health Department, National Institute for Health and Welfare, Kuopio, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Pekkanen
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: H J M
authors.initials: HJM
authors.lastname: Harmsen
authors.affiliation: Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland.|Respiratory, Inflammation and Autoimmunity, Innovative Medicine, AstraZeneca R & D, Mölndal, Sweden.
authors.forename: O
authors.initials: O
authors.lastname: Vaarala
mesh_terms: D000367:Age Factors; D001249:Asthma / Q000453:epidemiology* / Q000209:etiology / Q000378:metabolism*; D001419:Bacteria; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003876:Dermatitis, Atopic / Q000453:epidemiology* / Q000209:etiology / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism; D007223:Infant; D016753:Interleukin-10 / Q000378:metabolism; D007410:Intestinal Diseases / Q000453:epidemiology* / Q000378:metabolism*; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D016017:Odds Ratio; D011247:Pregnancy; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D016753:Interleukin-10
keywords: Escherichia; Lactobacillaceae; asthma; atopic dermatitis; children; colonization; farming; fecal calprotectin; lipopolysaccharide