Abstract and Introduction
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.
Introduction
Allergies are characterized by exaggerated immune responses to foreign antigens from non-pathogenic substances. The prevalence of atopic individuals in industrialized countries has been steadily increasing over the past 50 years,[1] yet surprisingly no single factor is clearly responsible for this phenomenon. Over a similar time frame, there has not been an appreciable increase in allergic disease incidence in developing countries, suggesting that environmental aspects of the industrialized lifestyle are responsible for the allergy pandemic. Air pollution, dietary changes, the absence of helminth colonization and antibiotic use have all been implicated in the rise of allergic disease prevalence.[1,2]
The 'hygiene hypothesis' was conceived following the observation that a larger family size reduced the risk of developing hay fever.[3] This hypothesis proposed that an absence of infection early in life results in a lack of proper immune system education, leading to aberrant responses when harmless antigens are encountered later in life.[1] More recently, an alternative hypothesis has been proposed to explain the epidemiological data: the 'microbiota hypothesis'.[4] This hypothesis suggests that it is the composition of species within the intestinal microbiota of mammals that drives the development of atopy. Evidence for this hypothesis stems from correlations between microbiota composition and allergic disease development, both in humans and mice,[4] and from the wealth of literature describing the contributions of the microbiota toward immune development and immune cell differentiation.[5] Several of the factors implicated in the epidemiological shifts in allergy development, including diet, helminth infections and antibiotic use have been shown to modify the composition of the microbiota.[4,6]
In this review, we focus on the 'microbiota hypothesis' of allergic disease, and discuss evidence for the use of antibiotics disrupting the microbiota, resulting in the development of allergies at mucosal sites. Current insights into the mechanisms of antibiotic treatment-mediated allergy development, as well as strategies to reduce microbiota perturbations during antibiotic therapy, are discussed.
Expert Rev Clin Immunol. 2013;9(11):1019-1030. © 2013 Expert Reviews Ltd.
