Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis

Abstract

Persistent mucosal inflammation and microbial infection are characteristics of chronic rhinosinusitis (CRS). Mucosal microbiota dysbiosis is found in other chronic inflammatory diseases; however, the relationship between sinus microbiota composition and CRS is unknown. Using comparative microbiome profiling of a cohort of CRS patients and healthy subjects, we demonstrate that the sinus microbiota of CRS patients exhibits significantly reduced bacterial diversity compared with that of healthy controls. In our cohort of CRS patients, multiple, phylogenetically distinct lactic acid bacteria were depleted concomitant with an increase in the relative abundance of a single species, Corynebacterium tuberculostearicum. We recapitulated the conditions observed in our human cohort in a murine model and confirmed the pathogenic potential of C. tuberculostearicum and the critical necessity for a replete mucosal microbiota to protect against this species. Moreover, Lactobacillus sakei, which was identified from our comparative microbiome analyses as a potentially protective species, defended against C. tuberculostearicum sinus infection, even in the context of a depleted sinus bacterial community. These studies demonstrate that sinus mucosal health is highly dependent on the composition of the resident microbiota as well as identify both a new sino-pathogen and a strong bacterial candidate for therapeutic intervention.

Fig. 1

Comparative analyses of bacterial community. (A to C) Richness (A), evenness (B), and Shannon diversity (C) indices of array-detected sinus microbiota of CRS patients and healthy subjects. Values represent means ± SEM. (D) Hierarchal cluster analysis based on a Canberra distance matrix of microbiota detected in CRS patients and healthy subjects. Significant clusters determined with approximately unbiased (au) P values and bootstrap values (bp) are indicated. A heat plot of sinus symptom severity based on SNOT-20 scores and use of preoperative antimicrobials are also indicated (details provided in Table 1).

Fig. 2

Phylogenetic tree demonstrating the breadth of bacterial community members exhibiting significant positive or negative correlations with sinus symptom severity (determined by SNOT-20 score).

Fig. 3

(A) Depletion of sinus microbiome and instillation of C. tuberculostearicum induce overt sinus pathology. PAS-stained histological sections of murine sinuses representative of animals in each treatment group treated with a combination of antibiotic and C. tuberculostearicum. Triplicate views of maxillary sinuses from two mice per treatment group were used to determine physiology (representative images are shown; panels i to iv). Mice treated with a combination of antibiotic and C. tuberculostearicum exhibit evidence of significantly increased goblet cell hyperplasia (indicated by arrows) and mucin hyper-secretion compared to other treatment groups (panel iii). (B) Enumeration of goblet cells across murine treatment groups (n = 3 animals per group). Values represent means ± SEM.

Fig. 4

(A) L. sakei protects sinus mucosa from C. tuberculostearicum–induced pathogenesis. PAS-stained histological sections of murine sinuses representative of animals in each treatment group at ×60 magnification (panels i to v). Triplicate views of maxillary sinuses from two mice per treatment group were used to determine physiology (representative images are shown). (B) Enumeration of goblet cells across murine treatment groups (n = 3 animals per group). Values represent means ± SEM.