A case for antibiotic perturbation of the microbiota leading to allergy development

Abstract

The use of antibiotics to treat pathogenic bacterial infections has been one of the greatest contributions to human health, yet antibiotic use also perturbs the communities of commensal and symbiotic bacteria that reside in the intestine of mammals. The microbiota are critical for normal immune development and for maintaining intestinal homeostasis, and disruption of the microbiota has been linked to the emergence of allergic disease both in humans and in animal models. The evidence and mechanisms for antibiotic-mediated disruptions leading to the onset of allergic disease at mucosal surfaces is discussed, as well as the future challenges for the field. A more complete understanding of the mechanisms by which the intestinal microbiota modulate allergic disease development will allow for interventions to counter the potentially adverse effects of antibiotic treatment on the microbiota.

Keywords::

• allergy
• antibiotics
• asthma
• bone marrow progenitors
• epigenetics
• immune development
• metabolites
• microbiota
• probiotics

Acknowledgements

The authors would like to thank Stephen A Redpath for artwork, as well as Eric M Brown, Henry J McSorley, Shannon L Russell, Yanet Valdez and Marta Wlodarska for critical revision of this manuscript.

Financial & competing interests disclosure

Work in the authors' laboratory was funded by a Canadian Institutes of Health Research (CIHR) Emerging Team Grant in partnership with Genome BC and the AllerGen NCE. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • The incidence of allergic disease is increasing in industrialized countries.

• • Several factors that are implicated in this epidemiological phenomenon, including the use of antibiotics, involve modulation of the intestinal microbiota composition.

• • Antibiotic use, particularly early in life, can lead to a long lasting perturbation in microbiota composition.

• • Human studies have identified antibiotic use in the first year of life as a risk factor for the development of allergic asthma, and murine studies have confirmed that modulation of the neonatal microbiota composition by antibiotic treatment can exacerbate the severity of airway inflammation in experimental asthma models.

• • Murine studies have shown that the absence or manipulation of the microbiota early in life can lead to persistent alterations in immunoglobulin E release, epigenetic modifications, invariant natural killer T cell recruitment, and Treg frequencies.

• • Both human and murine studies have found the class of antibiotic used is important in determining the impact on allergic disease, supporting the hypothesis that it is specific members of the microbiota that are responsible for modulating allergy development or exacerbation.

• • The microbiota or metabolites derived from the microbiota could modulate allergic disease through affecting epigenetic regulation, by directly altering mature immune cell function, by affecting immune cell progenitor frequencies or by altering the susceptibility to infections.

• • The relative contributions of the respiratory or intestinal microbiota toward allergy development have yet to be determined.

• • Probiotic strategies to prevent asthma development have had little success in humans, but have shown some promise in murine studies.

• • Further characterization of the mechanisms by which specific components of the microbiota alter immune function will be critical, to better design therapeutic microbiota combinations or microbiota-derived products which can be used to mitigate the adverse effects of antibiotics on allergic disease development.

Notes