Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing

Background: Improved hygiene has altered early microbial exposure by reduci ng childhood infections, which has been suggested as a cause for the contin uously rising prevalence of atopic diseases. On the basis of both intensity and timing of stimulus, it has been hypothesized that exposure to commensa l microflora may represent another key protective modulator of immunity aga inst atopy and subsequent atopic diseases. Objective: We sought to investigate whether differences in early gut microf lora precede the later development of atopic sensitization. Methods: Intestinal microflora from 76 infants at high risk of atopic disea ses were analyzed at 3 weeks and 3 months of age by using conventional bact erial cultivation and 2 culture-independent methods, gas-liquid chromatogra phy of bacterial cellular fatty adds and quantitative fluorescence in situ, hybridization of bacterial cells. Infants evincing at least one positive s kin 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 m ore 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. Conclusion: Differences In the neonatal gut microflora precede the developm ent of atopy, suggesting a crucial role of the balance of indigenous intest inal bacteria for the maturation of human immunity to a nonatopic mode.