The microbiome in allergic disease: Current understanding and future opportunities-2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology

Abstract

PRACTALL is a joint initiative of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology to provide shared evidence-based recommendations on cutting-edge topics in the field of allergy and immunology. PRACTALL 2017 is focused on what has been established regarding the role of the microbiome in patients with asthma, atopic dermatitis, and food allergy. This is complemented by outlining important knowledge gaps regarding its role in allergic disease and delineating strategies necessary to fill these gaps. In addition, a review of progress in approaches used to manipulate the microbiome will be addressed, identifying what has and has not worked to serve as a baseline for future directions to intervene in allergic disease development, progression, or both.

Keywords: Microbiome; asthma; atopic dermatitis; dysbiosis; food allergy; microbiota; prebiotic; probiotic; systems biology.

FIG 1

Microbial ecology. The human body provides a diverse habitat for the microbes that reside on its epithelial surfaces. Differences in oxygen levels, pH, and availability of nutrients create environments that select for the microbes specifically adapted to colonize the tissue. However, the human body ecosystem is dynamic, with changes driven by age, diet, environmental exposures, and disease. Nutrients provided from diet are key ecological influencers within the intestinal tract because they represent energy sources for bacteria that have the metabolic machinery to use them. Diet changes with both age and lifestyle matched by a coordinated change in the constituents of the microbiota. Inflammation is a powerful modifier of the local microbial habitat both directly through antimicrobial immune mechanisms and indirectly by influencing putative energy sources such as mucins. Physiologic changes, including pH or oxygen levels, change the environment, providing microbes with the toolkit to handle these microenvironments. Host-microbe cross-talk is a key determinant of the tissue habitat. Tonic signals from the microbiota set the tone of the local immune system, which, under steady-state conditions, results in a state of mutualism; however, dysregulation of this interaction, such as through exposure to an exogenous pathogen (or a bloom of a pathobiont), medical treatment (antibiotics, antifungal drugs, and immunosuppression), or inflammation/tissue damage, can perpetuate inflammation or cause exacerbations. DAMPS, Danger-associated molecular patterns; PAMPs, pathogen-associated molecular patterns.

FIG 2

Moving toward a systems biology view of the microbiome in asthma and allergy. The colored circular nodes represent microbial, genetic, regulatory, metabolite, and environmental entities associated with asthma and allergic disorders. Their identification and potential connectivity can be assessed by the profiling represented in the large rectangular nodes. The green rectangular nodes represent diseases of interest. Orange lines (edges) denote evidence for associations between the implicated nodes in asthma and allergy. Dashed blue edges denote relationships that are currently less well studied. Examination of the network’s collective nodes and edges or a substantial subset thereof would move us toward a systems biology understanding of allergic disease. Figure adapted from Bunyavanich and Schadt.