The microbiome in asthma

Abstract

Purpose of review: Asthma is a complex and heterogeneous disease with strong genetic and environmental components that manifests within a variety of clinical features and diverse patterns of immune responses. Asthma prevalence has dramatically increased over the last decade in Westernized societies, thereby suggesting a key function of environmental factors in disease promotion and development.

Recent findings: 'Early-life' microbial exposure and bacterial colonization are crucial for the maturation and the education of the immune system. The commensal flora is also critical in order to maintain immune homeostasis at the mucosal surfaces and may consequently play an important function in allergic disease development. Recent evidence demonstrates that asthma influences and is also impacted by the composition and function of the human intestinal and respiratory microbiome.

Summary: In this review, we summarize the most recent findings on how asthma development is connected with respiratory and intestinal microbial dysbiosis. We highlight and discuss recent research that reveals the existence of a 'gut-lung' microbial axis and its impact on asthma development. We also analyze how 'early-life' microbial exposure affects the immune response and the consequences for asthma development.

Figure 1. Asthma heterogeneity and immunological patterns involved in disease pathology

(A) The Th2^high endotype is characterized by increased activation of DCs, Th2 CD4⁺ T cells, ILC2s and B cells which result in heightened allergen-specific IgE and Th2 cytokine production as well as elevated numbers of lung infiltrating and circulating eosinophils. On the other hand, the Th2^low endotype display reduced activation of Th2 cells and Th2 cytokine production as well as decreased numbers of eosinophils. (B) Intrinsic non-allergic and steroid resistant asthma is IgE and Th2 independent, associated with a Th1/Th17 immune response and the participation of ILC3s as well as intense neutrophils recruitment in the lungs.

Figure 2. Environmental factors influencing asthma development

The continuous rise in asthma incidence in “westernized” societies cannot be only attributed to a genetic component alone; environmental factors resulting from a modern lifestyle are involved in this increased prevalence. The composition of the microbial flora is constantly fluctuating and strongly influenced by environmental factors. Microbial dysbiosis can be triggered by stress, the modern-lifestyle diet, antibiotic use, birth and feeding mode. By promoting the growth of pathogenic bacteria, microbial dysbiosis will also prevent early exposure to health-promoting bacteria. In genetically predisposed hosts, this alteration in microbial communities will promote the development of asthma.