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

Expert Commentary & Five-year View

Human epidemiology data have been revealing, but it is murine experiments that have solidified the link between antibiotic perturbation of the microbiota and exacerbated airway inflammation. The intestinal microbiota and the mammalian immune system have co-evolved for millions of years, and it is clear that in a healthy host, bi-directional regulation between these components exists,[93] and moreover, these interactions depend on a host-specific microbiota.[94] Disrupting this delicate balance disturbs immune homeostasis and in some individuals may result in development of allergies, which appears to be dependent on the timing of microbiota disruption, the extent of the perturbation and the stability of the original microbiota.

In the past decade, our understanding of the microbiota has improved tremendously, due to genomic, transcriptomic, proteomic and metabolomic advances. A flurry of studies have described associations between the composition of the microbiota and susceptibility to allergic and inflammatory diseases,[5] and the field is gradually moving toward describing how the functional capacity of the microbiota, rather than simply the presence of individual species, correlates with disease state.[95] An increasing number of studies have moved from describing associations to confirming that the microbiota can have a direct role in altering immune homeostasis, and several mechanisms by which the microbiota can exert its effects have been described. Validating mechanisms of immune modulation by the microbiota will be challenging, as it is likely that multiple complex interactions exist, that will be dependent on host diet, genotype and age. Additionally, care must be taken in generalizing mechanisms which exist in different experimental settings – it should be kept in mind that the absence of a microbiota during development, antibiotic-depleted and antibiotic-shifted mouse models may present similar phenotypes, yet the pathways by which these phenotypes develop may be starkly different.

It appears that certain classes of antibiotic are associated with a heightened risk of disease development,[49,52,60] and if this phenomenon can be directly confirmed, then the prescription of these drugs can be avoided where other lower-risk antibiotics are available.

An important area for future focus will be to characterize those immune disruptions following early-life antibiotic treatment that persist into adulthood, and to confirm what the critical window for recovery of these perturbations is. Probiotic treatment in humans has shown little promise to date in reducing the risk of allergy development, however it is possible that a beneficial effect would be seen, if the correct mix of bacteria are administered at the time of antibiotic-mediated microbiota disruption. The characterization of the production and function of metabolites derived from the microbiota is an area of additional therapeutic promise.[62]

Antibiotic disruption of the microbiota has been associated with the onset of many inflammatory, infectious and metabolomic conditions, in addition to allergic disease development and exacerbation.[32] A more thorough understanding of the mechanisms by which microbial species and their metabolites modulate immune cells will likely reveal additional pathways which can be therapeutically targeted during antibiotic disruption, to mitigate their potentially detrimental effects.

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