title: Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.
abstract: BACKGROUND
  Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known.
  
  
  OBJECTIVE
  Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy-prone infants.
  
  
  METHODS
  In a randomized double-blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C-reactive protein (CRP), total IgA and IgE, food-specific IgA, IgG, and IgE, IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years.
  
  
  RESULTS
  Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL-10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17-0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16-0.87), P=0.023] at age 2 years, when adjusted with probiotic use.
  
  
  CONCLUSIONS
  The association of CRP with a decreased risk of eczema at 2 years of age in allergy-prone children supports the view that chronic, low-grade inflammation protects from eczema. Probiotic-induced low-grade inflammation was characterized by elevation of IgE, IgA, and IL-10, the changes typically observed in helminth infection-associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.
authors.affiliation: The Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. emma.marschan@hus.fi
authors.forename: E
authors.initials: E
authors.lastname: Marschan
authors.forename: M
authors.initials: M
authors.lastname: Kuitunen
authors.forename: K
authors.initials: K
authors.lastname: Kukkonen
authors.forename: T
authors.initials: T
authors.lastname: Poussa
authors.forename: A
authors.initials: A
authors.lastname: Sarnesto
authors.forename: T
authors.initials: T
authors.lastname: Haahtela
authors.forename: R
authors.initials: R
authors.lastname: Korpela
authors.forename: E
authors.initials: E
authors.lastname: Savilahti
authors.forename: O
authors.initials: O
authors.lastname: Vaarala
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis; D002675:Child, Preschool; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D004485:Eczema / Q000175:diagnosis / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000517:prevention & control* / Q000628:therapy; D007070:Immunoglobulin A / Q000097:blood; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D007249:Inflammation / Q000276:immunology*; D016017:Odds Ratio; D010641:Phenotype; D010919:Placebos; D011237:Predictive Value of Tests; D011247:Pregnancy; D019936:Probiotics / Q000008:administration & dosage*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012882:Skin Tests
chemical_list: D016207:Cytokines; D007070:Immunoglobulin A; D010919:Placebos; D007073:Immunoglobulin E; D002097:C-Reactive Protein