A Case for Antibiotic Perturbation of the Microbiota Leading to Allergy Development

Lisa A Reynolds; B Brett Finlay

Disclosures

Expert Rev Clin Immunol. 2013;9(11):1019-1030. 

In This Article

Impact of Antibiotics on Susceptibility to Infection

As well as stimulating normal immune development, the intestinal microbiota help prevent enteric infections by bacterial, viral or fungal agents. This is achieved by physically contributing to the mucus layers, by producing and stimulating host-production of antimicrobial peptides, by priming innate immune cells and by competing with invading organisms for nutrients.[38–40]

A common result of antibiotic use in humans is the acquisition of opportunistic fungal infections. It has been proposed that disruption of the microbiota leads to an increase in fungal colonization which contributes to increased sensitivity to antigen exposure, leading to allergy development or exacerbation. In a mouse model, treatment with the broad-spectrum antibiotic cefoperazone for 5 days, followed by oral gavage with Candida albicans, results in an altered bacterial composition and an increase in intestinal fungal colonization.[41] These mice respond to nasal administration of the mold spore Aspergillus fumigatus conidia by production of IL-5, IL-13, IFN-γ, eosinophilia and mast cell expansion in the lungs, and heightened circulating IgE levels.[41,42] Notably, in mice that have not been antibiotic-treated, or received a C. albicans gavage, this inflammatory response to A. fumigatus is absent,[41,42] suggesting that tolerance to intranasal antigen exposure is lost following antibiotic treatment and fungal colonisation. Additionally, following antibiotic treatment, the reassembly of bacterial communities is altered in the presence of fungal colonisation,[43] suggesting that if opportunistic infections occur, they can prolong antibiotic-mediated disruption of the bacterial microbiota.

In both GF mice, and in conventionally housed mice treated with a broad-spectrum antibiotic cocktail, impaired immunity to respiratory viral infections is seen, resulting in higher pulmonary viral titres.[38,39] This is of importance, since many asthma exacerbations in humans correlate with viral infections.[44] Additionally, in mice, concurrent viral infections early in life result in attenuated tolerance to administered antigens.[45]

Opportunistic infections following antibiotic treatment may be a contributing factor at either the antigen sensitization stage of allergy development, or a cause of asthma exacerbations. It will be important to resolve whether it is the absence of key bacterial species in the intestine, or the presence of opportunistic pathogens such as fungi or viruses following antibiotic treatment which results in a lack of tolerance. Care must be taken when drawing conclusions about the effect of a reduced bacterial burden following antibiotic treatment, when the levels of fungal or viral colonization have not been assessed.

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