title: Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing.
abstract: BACKGROUND
  Improved hygiene has altered early microbial exposure by reducing childhood infections, which has been suggested as a cause for the continuously rising prevalence of atopic diseases. On the basis of both intensity and timing of stimulus, it has been hypothesized that exposure to commensal microflora may represent another key protective modulator of immunity against atopy and subsequent atopic diseases.
  
  
  OBJECTIVE
  We sought to investigate whether differences in early gut microflora precede the later development of atopic sensitization.
  
  
  METHODS
  Intestinal microflora from 76 infants at high risk of atopic diseases were analyzed at 3 weeks and 3 months of age by using conventional bacterial cultivation and 2 culture-independent methods, gas-liquid chromatography of bacterial cellular fatty acids and quantitative fluorescence in situ hybridization of bacterial cells. Infants evincing at least one positive skin prick reaction at 12 months were grouped as atopic subjects, and those without positive reactions were grouped as nonatopic subjects.
  
  
  RESULTS
  Atopic sensitization was observed in 22 (29%) of 76 children. At 3 weeks, the bacterial cellular fatty acid profile in fecal samples differed significantly between infants in whom atopy was and was not developing (P =.005). By using fluorescence in situ hydridization, atopic subjects had more clostridia (geometric mean [95% confidence interval]: 9.3 x 10(7) [3.8-22.9 x 10(7)] vs 3.3 x 10(7) [1.8-6.1 x 10(7)], P =.04) and tended to have fewer bifidobacteria (1.8 x 10(9) [0.4-7.6 x 10(9)] vs 6.1 x 10(9) [2.5-14.6 x 10(9)], P =.11) in their stools than nonatopic subjects, resulting in a reduced ratio of bifidobacteria to clostridia (P =.03). The differences were not detected by bacterial cultivation.
  
  
  CONCLUSIONS
  Differences in the neonatal gut microflora precede the development of atopy, suggesting a crucial role of the balance of indigenous intestinal bacteria for the maturation of human immunity to a nonatopic mode.
authors.affiliation: Department of Pediatrics, University of Turku, Turku.
authors.forename: M
authors.initials: M
authors.lastname: Kalliomäki
authors.forename: P
authors.initials: P
authors.lastname: Kirjavainen
authors.forename: E
authors.initials: E
authors.lastname: Eerola
authors.forename: P
authors.initials: P
authors.lastname: Kero
authors.forename: S
authors.initials: S
authors.lastname: Salminen
authors.forename: E
authors.initials: E
authors.lastname: Isolauri
mesh_terms: D006801:Humans; D006969:Hypersensitivity, Immediate / Q000453:epidemiology / Q000209:etiology* / Q000382:microbiology*; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D015995:Prevalence; D013270:Stomach / Q000382:microbiology*