Influences on allergic mechanisms through gut, lung, and skin microbiome exposures
Andrea M. Kemter, Cathryn R. Nagler
Andrea M. Kemter, Cathryn R. Nagler
Published February 25, 2019
Citation Information: J Clin Invest. 2019;129(4):1483-1492. https://doi.org/10.1172/JCI124610.
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Review Series

Influences on allergic mechanisms through gut, lung, and skin microbiome exposures

Abstract

In industrialized societies the incidence of allergic diseases like atopic dermatitis, food allergies, and asthma has risen alarmingly over the last few decades. This increase has been attributed, in part, to lifestyle changes that alter the composition and function of the microbes that colonize the skin and mucosal surfaces. Strategies that reverse these changes to establish and maintain a healthy microbiome show promise for the prevention and treatment of allergic disease. In this Review, we will discuss evidence from preclinical and clinical studies that gives insights into how the microbiota of skin, intestinal tract, and airways influence immune responses in the context of allergic sensitization.

Authors

Andrea M. Kemter, Cathryn R. Nagler

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Figure 3

Exposure to a healthy microbiota drives antiinflammatory homeostatic conditions in the airways, while dysbiosis and viral respiratory tract infections can induce type 2 inflammation.

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Exposure to a healthy microbiota drives antiinflammatory homeostatic con...
It has become apparent in recent years that bacteria can also be found in a healthy respiratory tract, with decreasing community richness in the lower airways. Commensal colonization induces the differentiation of peripheral Tregs that are crucial for the control of type 2 immune responses. The presence of Proteobacteria increases the risk of developing asthma, partly as a result of an increased risk for viral infections, particularly in the lower airways. Viral infections induce the release of the alarmins TSLP, IL-33, and IL-25 from the airway epithelium, inducing type 2 inflammation. In addition, intestinal microbiome homeostasis influences airway immune responses. Metabolites like SCFAs can act systemically, for example affecting APC precursors in the bone marrow to give rise to APCs populating the airways that are less capable of inducing type 2 responses. On the other hand, proinflammatory metabolites of a dysbiotic intestinal microbiota can play a role in driving inappropriate immune responses. APC, antigen-presenting cell; ILC, innate lymphoid cell; SCFA, short-chain fatty acid; Treg, regulatory T cell; TSLP, thymic stromal lymphopoietin.