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 2

The healthy intestinal microbiota protects the intestinal barrier and promotes a tolerogenic microenvironment.

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The healthy intestinal microbiota protects the intestinal barrier and pr...
A healthy gut microbiota containing fiber-fermenting anaerobic commensals can induce the differentiation of T cells into Tregs via several different mechanisms. SCFAs induce GPCR signaling as well as inhibit HDACs within DCs and T cells. Essential vitamins produced by bacteria can be important for Treg survival, and bile acids, which are modified by the intestinal microbiota, inhibit APC activation. In addition, molecules like PSA produced by Bacteroides fragilis can also induce Treg differentiation. SCFA production also protects the intestinal barrier. Butyrate, for example, is an important energy source for colonocytes; its utilization drives local hypoxia, which in turn favors the anaerobic microbiota. Tryptophan metabolites can act as AhR ligands and induce the production of IL-22 by ILC3s. IL-22 acts on the epithelium to strengthen the intestinal barrier function, for example by induction of antimicrobial peptides or mucus production. Dietary antigens sampled in this environment will lead to tolerance induction rather than sensitization against the antigen. AhR, aryl hydrocarbon receptor; AMP, antimicrobial peptide; APC, antigen-presenting cell; GPCR, G protein–coupled receptor; HDAC, histone deacetylase; IEC, intestinal epithelial cell; ILC, innate lymphoid cell; LCFA, long-chain fatty acid; LN, lymph node; LPS, lipopolysaccharide; PSA, polysaccharide A; SCFA, short-chain fatty acid; Treg, regulatory T cell.