Heterogeneity of Microbiota Dysbiosis in Chronic Rhinosinusitis: Potential Clinical Implications and Microbial Community Mechanisms Contributing to Sinonasal Inflammation

Keehoon Lee, Steven D. Pletcher, Susan V. Lynch, Andrew N. Goldberg, Emily K. Cope

Recent studies leveraging next-generation sequencing and functional approaches to understand the human microbiota have demonstrated the presence of diverse, niche-specific microbial communities at nearly every mucosal surface. These microbes contribute to the development and function of physiologic and immunological features that are key to host health status. Not surprisingly, several chronic inflammatory diseases have been attributed to dysbiosis of microbiota composition or function, including chronic rhinosinusitis (CRS). CRS is a heterogeneous disease characterized by inflammation of the sinonasal cavity and mucosal microbiota dysbiosis. Inflammatory phenotypes and bacterial community compositions vary considerably across individuals with CRS, complicating current studies that seek to address causality of a dysbiotic microbiome as a driver or initiator of persistent sinonasal inflammation. Murine models have provided some experimental evidence that alterations in local microbial communities and microbially-produced metabolites influence health status. In this perspective, we will discuss the clinical implications of distinct microbial compositions and community-level functions in CRS and how mucosal microbiota relate to the diverse inflammatory endotypes that are frequently observed. We will also describe specific microbial interactions that can deterministically shape the pattern of co-colonizers and the resulting metabolic products that drive or exacerbate host inflammation. These findings are discussed in the context of CRS-associated inflammation and in other chronic inflammatory diseases that share features observed in CRS. An improved understanding of CRS patient stratification offers the opportunity to personalize therapeutic regimens and to design novel treatments aimed at manipulation of the disease-associated microbiota to restore sinus health.