Unraveling the role of the microbiome in chronic rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is a complex, heterogenous condition that is likely associated with infectious and inflammatory causative factors. Renewed interest in the role that microbes play in this condition has stemmed from advancements in microbe identification and parallel research implicating the microbiome as having a role in other chronic inflammatory conditions. This clinical commentary provides a review of the current literature relevant to chronic rhinosinusitis. Particular focus is placed on factors specific to investigation of the sinonasal microbiome, evidence for the role of dysbiosis in the disease state, and influences that may affect the microbiome. Possible mechanisms of disease and therapeutic implications through microbial manipulation are also reviewed, as are deficiencies and limitations of the current body of research.

Keywords: Microbiome; chronic rhinosinusitis; host-microbial interactions; microbiome manipulation; next-generation sequencing; probiotic; therapeutic intervention.

FIG 1.

Considerations for analysis of the sinonasal microbiota. A, Investigators must consider the clinical feasibility, benefits, and limitations of the site in the sinonasal cavity. B, Different sampling techniques must also be considered carefully. Negative controls (extraction blanks and blank swabs) can help to identify and reduce contamination. C, Commonly used techniques for microbiome analyses can be used to answer distinct research questions. Amplicon sequencing (eg, 16S rRNA gene sequencing) can yield insights into community composition. Shallow shotgun metagenomics allows for high resolution of the microbial species and strains, whereas deep shotgun metagenomics can yield insights into the putative functions in a community. Gene expression can be analyzed via RNA sequencing (of reverse-transcribed cDNA) to determine which microbial and host genes are expressed in a given condition. Functional analyses can quantify protein production (proteomics) or host- and microbiome-derived metabolites (metabolomics).

FIG 2.

Potential mechanisms for microbiota-regulated processes in CRS. A, Commensal bacteria are niche occupiers precluding colonization or overgrowth of potential pathogens. This can occur directly through the production of bacteriocins, or it may occur indirectly by competition for local resources or induction of various antimicrobial peptides from the apical epithelium. B, Commensal organisms are critical for immune maturation, as has been documented in mouse gut and upper airway studies. Gain of pathogens may direct proinflammatory imbalance over anti-inflammatory homeostatic immune activities. C, Commensal organisms may provide several metabolic actions in the complex apical surface milieu, including biosynthesis of important proteins, degradation of airborne or locally produced toxins to innocuous byproducts, and digestion of mucins into energy sources such as short chain fatty acids. D, Breakdown of the epithelial barrier is a hallmark of CRS, with translocation of microbes into the subepithelial compartment. This can propagate the proinflammatory state. PRR, Pathogen recognition; Treg, regulatory T.