A comprehensive review of the nasal microbiome in chronic rhinosinusitis (CRS)

Abstract

Chronic rhinosinusitis (CRS) has been known as a disease with strong infectious and inflammatory components for decades. The recent advancement in methods identifying microbes has helped implicate the airway microbiome in inflammatory respiratory diseases such as asthma and COPD. Such studies support a role of resident microbes in both health and disease of host tissue, especially in the case of inflammatory mucosal diseases. Identifying interactive events between microbes and elements of the immune system can help us to uncover the pathogenic mechanisms underlying CRS. Here we provide a review of the findings on the complex upper respiratory microbiome in CRS in comparison with healthy controls. Furthermore, we have reviewed the defects and alterations of the host immune system that interact with microbes and could be associated with dysbiosis in CRS.

Figure 1. A Model for changes in the nasal microbiome and mucosal immune response in CRSwNP

Although multiple microorganisms colonize healthy nasal mucosa membranes, as shown in the top figure, there are changes that occur in the microbiome in patients with CRSwNP, including increased S. aureus abundance, decreased Bacteriodetes and decreased diversity, as shown in the bottom figure. These changes, along with loss of epithelial integrity, decreased pattern recognition molecules, decreased mucosal glands and decreased antimicrobial peptide production in the nasal polyp and sinus tissue, can potentially provide an environment that promotes invasion of microorganisms across the mucosal barrier. Enterotoxins produced by S. aureus can act as superantigens and promote Th-2 inflammation, resulting in production of cytokines such as IL-13, IL-4 and IL-5 that further recruit and activate inflammatory cells such as eosinophils, mast cells, basophils and alternatively activated macrophages. Bacterial and fungal proteases can induce production of thymic stromal lymphopoietin (TSLP) through Protease-Activated Receptor-2(PAR-2)[151], which will subsequently result in activation of innate lymphoid type 2 cells (ILC-2) that further produce IL-5 and IL-13.