title: The microbiome and development of allergic disease.
abstract: OBJECTIVE
  First, to review how the global rise in prevalence of asthma prompted studies of the relationships between microbial exposure in early infancy, the rate and pattern of development of immune function, and the development of allergic sensitization and of wheezing in childhood. And, second, to review how those studies laid the groundwork for a possible strategy for primary prevention of asthma through manipulation of the microbiome of the gastrointestinal and/or respiratory tracts.
  
  
  RESULTS
  Atopy and asthma are complex diseases thought to result from a 'gene-by-environment' interaction; the rapidity of their rise in prevalence points to a change in environment as most likely causal. Epidemiologic studies noting associations between events in infancy and later development of atopic diseases have suggested that their rise in prevalence is related to a deficiency in microbial exposure in early life. The findings from birth cohort studies of humans and from interventional studies of mice converge in suggesting that a deficiency in microbial colonization of the respiratory or gastrointestinal tract by certain commensal microbes results in skewed development of systemic and/or local immune function that increases susceptibility to allergic sensitization and to viral lower respiratory infection. Recent studies are now honing in on identifying the microbes, or collection of microbes, whose collective functions are necessary for induction of immune tolerance, and thus of reduced susceptibility.
  
  
  CONCLUSIONS
  Atopy and asthma appear to have their roots in an insufficiency of early-life exposure to the diverse environmental microbiota necessary to ensure colonization of the gastrointestinal and/or respiratory tracts with the commensal microbes necessary for induction of balanced, toleragenic immune function. Identification of the commensal bacteria necessary, now ever closer at hand, will lay the groundwork for the development of strategies for primary prevention of atopic disease, especially of childhood asthma.
authors.affiliation: aDivision of Gastroenterology bDivision of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Lynch
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
mesh_terms: D000818:Animals; D001249:Asthma / Q000209:etiology / Q000382:microbiology*; D001691:Biological Therapy; D004781:Environmental Exposure / Q000009:adverse effects; D059647:Gene-Environment Interaction; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000382:microbiology*; D007107:Immune System / Q000382:microbiology*; D007108:Immune Tolerance; D007223:Infant; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D064307:Microbiota; D012137:Respiratory System / Q000382:microbiology*