Reviews and feature article
The microbiome in asthma

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The application of recently developed sensitive, specific, culture-independent tools for identification of microbes is transforming concepts of microbial ecology, including concepts of the relationships between the vast complex populations of microbes associated with ourselves and with states of health and disease. Although most work initially focused on the community of microbes (microbiome) in the gastrointestinal tract and its relationship to gastrointestinal disease, interest has expanded to include study of the relationships of the airway microbiome to asthma and its phenotypes and to the relationships between the gastrointestinal microbiome, development of immune function, and predisposition to allergic sensitization and asthma. Here we provide our perspective on the findings of studies of differences in the airway microbiome between asthmatic patients and healthy subjects and of studies of relationships between environmental microbiota, gut microbiota, immune function, and asthma development. In addition, we provide our perspective on how these findings suggest the broad outline of a rationale for approaches involving directed manipulation of the gut and airway microbiome for the treatment and prevention of allergic asthma.

Section snippets

The airway microbiome in asthma

The idea that bronchial infection might underlie asthma was fostered by epidemiologic studies reporting an association between the development of bronchitis or pneumonia during community outbreaks of Chlamydophila pneumoniae and adult-onset asthma.19 These findings echoed earlier reports that treatment with a macrolide antibiotic was effective in patients with “chronic infectious asthma,”20 the term then applied to asthma associated with chronic mucus hypersecretion that worsens with asthma

The role of environmental and gut microbiota in asthma

Many of the early-life practices, conditions, and exposures associated with lower rates of allergy and asthma seem likely to increase the burden and diversity of exposure to microbes in infancy. These include residence in countries with a predominantly agrarian economy,41 having multiple older siblings,6 breast-feeding,42 growing up in close contact with farm animals,7, 8, 9 early day care attendance,43 consuming farm milk or contaminated water,10, 44 and growing up with pet dogs.11 Some

Relationships of gut microbiota to response to viral respiratory tract infection

In addition to shaping the risk of allergic sensitization, the gut microbiota can also shape responses to viral respiratory tract infection in infancy. The importance of such infections in early life to asthma development was strikingly shown in the Childhood Origins of Asthma Study, a birth cohort study of children of parents with allergies or asthma. Among these children, becoming ill from a viral respiratory tract infection, especially one that is rhinovirus related, in the first year of

Interaction of exposures to environmental allergens and microbes

The observations summarized above can be interpreted as suggesting a causal pathway linking environmental exposures in early infancy to the development of allergy and asthma: (1) environmental exposures shape the composition of the gut microbiota, (2) gut microbiota shape the rate and pattern of development of immune function, and (3) differences in immune function shape the nature and intensity of responsiveness to allergens and viruses encountered. A modification of this argument would be

Microbiome-host relationships in asthma: Key concepts and future challenges

The concept of a “common mucosal immune system” rests on the premise that there is cross-talk between human mucosal compartments and that microbially driven differences in mucosal immune function can be shared across sites. It is also likely true that local immune function, both innate and adaptive, also influences microbiome constitution. Once microbes enter a niche and become established, a balance must be struck that maintains functional homeostasis between the microbiome and the host. This

References (74)

  • I.I. Ivanov et al.

    Induction of intestinal Th17 cells by segmented filamentous bacteria

    Cell

    (2009)
  • M.J. Holtzman et al.

    Immune pathways for translating viral infection into chronic airway disease

    Adv Immunol

    (2009)
  • C.H. Razi et al.

    The immunostimulant OM-85 BV prevents wheezing attacks in preschool children

    J Allergy Clin Immunol

    (2010)
  • R. Luoto et al.

    Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: a randomized, placebo-controlled trial

    J Allergy Clin Immunol

    (2014)
  • J.E. Gern

    The Urban Environment and Childhood Asthma study

    J Allergy Clin Immunol

    (2010)
  • S.V. Lynch et al.

    Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children

    J Allergy Clin Immunol

    (2014)
  • Structure, function and diversity of the healthy human microbiome

    Nature

    (2012)
  • A. Morris et al.

    Comparison of the respiratory microbiome in healthy nonsmokers and smokers

    Am J Respir Crit Care Med

    (2013)
  • E.S. Charlson et al.

    Topographical continuity of bacterial populations in the healthy human respiratory tract

    Am J Respir Crit Care Med

    (2011)
  • J.R. Erb-Downward et al.

    Analysis of the lung microbiome in the “healthy” smoker and in COPD

    PLoS One

    (2011)
  • M. Hilty et al.

    Disordered microbial communities in asthmatic airways

    PLoS One

    (2010)
  • D.P. Strachan

    Hay fever, hygiene, and household size

    BMJ

    (1989)
  • M.J. Ege et al.

    Exposure to environmental microorganisms and childhood asthma

    N Engl J Med

    (2011)
  • M. Waser et al.

    Inverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe

    Clin Exp Allergy

    (2007)
  • D.R. Ownby et al.

    Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age

    JAMA

    (2002)
  • T. Olszak et al.

    Microbial exposure during early life has persistent effects on natural killer T cell function

    Science

    (2012)
  • S. Rautava et al.

    Microbial contact during pregnancy, intestinal colonization and human disease

    Nat Rev Gastroenterol Hepatol

    (2012)
  • S.L. Russell et al.

    Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma

    EMBO Rep

    (2012)
  • C. Czerkinsky et al.

    IgA antibody-producing cells in peripheral blood after antigen ingestion: evidence for a common mucosal immune system in humans

    Proc Natl Acad Sci U S A

    (1987)
  • H. Kiyono et al.

    NALT- versus Peyer's-patch-mediated mucosal immunity

    Nat Rev Immunol

    (2004)
  • J. Mestecky

    The common mucosal immune system and current strategies for induction of immune responses in external secretions

    J Clin Immunol

    (1987)
  • D.L. Hahn et al.

    Association of Chlamydia pneumoniae (strain TWAR) infection with wheezing, asthmatic bronchitis, and adult-onset asthma

    JAMA

    (1991)
  • M.A. Kaplan et al.

    The use of triacetyloleandomycin in chronic infectious asthma

    Antibiot Annu

    (1958)
  • M. Kraft et al.

    Detection of Mycoplasma pneumoniae in the airways of adults with chronic asthma

    Am J Respir Crit Care Med

    (1998)
  • P.N. Black et al.

    Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae

    Am J Respir Crit Care Med

    (2001)
  • H. Bisgaard et al.

    Childhood asthma after bacterial colonization of the airway in neonates

    N Engl J Med

    (2007)
  • H. Bisgaard et al.

    Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study

    BMJ

    (2010)
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    Disclosure of potential conflict of interest: Y. J. Huang's and H. A. Boushey's institutions have received funding for studies of the microbiome in asthma from the National Institutes of Health (Y. J. Huang from the National Heart, Lung, and Blood Institute [NHLBI; 105572] and H. A. Boushey from NHLBI U10 HL098115 and the National Institute of Allergy and Infectious Disease [1 UM1 AI114271-01 and P01 AI089473]). Within the past 3 years, H. A. Boushey has received a consultancy fee from Janssen; a grant from Genentech for study of “The Airway Microbiome of Severe Asthma” (A118451); payment for delivering lectures from the Allergy, Asthma, and Immunology Foundation of Northern California; and royalties from McGraw-Hill.

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