Reduced Diversity of the Intestinal Microbiota During Infancy Is Associated With Increased Risk of Allergic Disease at School Age

PURPOSE OF THE STUDY.
To investigate the potential association between the diversity of neonatal intestinal microbiota and the development of atopic disorders in childhood.
STUDY POPULATION.
Four hundred eleven infants born in Copenhagen to mothers with a history of asthma were enrolled from the years 1998 to 2001.
METHODS.
Infants had an initial visit at 1 month of age and were subsequently seen for a scheduled visit every 6 months until the age of 6 years. Atopic disease was assessed through examination by doctors at the clinical research unit with support from symptom diaries kept by the parents. Investigators conducted interval testing of peripheral blood eosinophil count, skin prick tests, and IgE testing. Infants’ microbiota were assessed through collection of fecal samples at 1 and 12 months of life. Polymerase chain reaction fragments from infant stool separated by DGGE (denaturing gradient gel electrophoresis) provided relative assessment of main bacterial strains and were used in assessing variety and richness in microbial genetic diversity. Cultures were used to identify bacteria, fungi, and yeast present in infant stool.
RESULTS.
In looking at trends associated with diversity of microbiota as measured by band richness on DGGE, investigators found that diversity of intestinal flora was inversely associated with allergic rhinitis (P = .007), allergic sensitization (serum specific IgE, P = .003, and skin prick test, P = .17), and peripheral blood eosinophil count (P = .34). Band richness at 1 month was not predictive of band richness at 12 months, but band richness at each point in time independently was associated with these measures of specified atopy. No significant association was found between band richness and development of asthma or atopic dermatitis. Particular bands seen on DGGE and specific microbiota isolated by culture were not significantly associated with clinical or laboratory evidence of atopic disease. Interestingly, it was noted that in children with culture positive for staphylococci, there was reduced band richness (14.8 vs 13.8) (P = .06). Additionally, risk for development of allergic sensitization was increased in infants with cultures positive for staphylococci at 1 month of age but not at 12 months.
CONCLUSIONS.
The authors concluded that increased bacterial diversity in infants’ intestinal flora reduced risk of allergic sensitization, allergic rhinitis, and peripheral blood eosinophilia. Although a particular bacterial strain was not found to be protective, results suggest that certain pathogenic bacteria such as Staphylococcus sp may increase risk for allergic disease, possibly through reduction in diversity of intestinal flora.
REVIEWER COMMENTS.
This study supports the association between decreased diversity of intestinal flora and development of allergic phenotype, specifically allergic sensitization, eosinophilia, and allergic rhinitis. It is interesting, however, that bacterial diversity in the intestinal flora was not associated with the development of asthma and atopic dermatitis. It might have been useful to look at the impact of intestinal microbiota on the development of food allergies. Additionally, the authors mainly focus on outcomes of the diversity of intestinal microbiota, without addressing mechanism or contributing factors. Future studies in this area may include development of food allergy as an outcome and address risk factors and potential interventions that promote or limit the diversity of infants’ intestinal microbiota and subsequent development of atopy.
- Copyright © 2012 by the American Academy of Pediatrics










