Determinants of the Nasal Microbiome: Pilot Study of Effects of Intranasal Medication Use

Abstract

Introduction: A role for bacteria and other microbes has long been suspected in the chronic inflammatory sinonasal diseases. Recent studies utilizing culture-independent, sequence-based identification have demonstrated aberrant shifts in the sinus microbiota of chronic rhinosinusitis subjects, compared with ostensibly healthy controls. Examining how such microbiota shifts occur and the potential for physician-prescribed interventions to influence microbiota dynamics are the topics of the current article.

Methods: The nasal cavity microbiota of 5 subjects was serially examined over an 8-week period using pan-bacterial 16S rRNA gene sequencing. Four of the subjects were administered topical mometasone furoate spray, while 1 subject underwent a mupirocin decolonization procedure in anticipation of orthopedic surgery.

Results: Measures of microbial diversity were unaffected by intranasal treatment in 2 patients and were markedly increased in the remaining 3. The increase in microbial diversity was related to clearance of Moraxella spp. and a simultaneous increase in members of the phylum Actinobacteria. Both effects persisted at least 2 weeks beyond cessation of treatment. Transient changes in the relative abundance of several bacterial genera, including Staphylococcus and Priopionibacteria, were also observed during treatment.

Conclusions: The effects of intranasal steroids on the sinonasal microbiome are poorly understood, despite their widespread use in treating chronic sinonasal inflammatory disorders. In this longitudinal study, administration of intranasal mometasone furoate or mupirocin resulted in shifts in microbial diversity that persisted to some degree following treatment cessation. Further characterization of these effects as well as elucidation of the mechanism(s) underlying these changes is needed.

Keywords: anterior nares; bacteria; microbiome; nasal steroid; rhinitis; sinusitis.

Figure 1.

Changes in nasal microbiota accompanying INS and mupirocin treatment. Relative abundances of nasal bacterial genera are summarized as mean values for pre-, intra-, and posttreatment samples. For simplicity of display, only genera with mean relative abundances greater than 0.5% across all specimens are displayed; rare taxa are aggregated into the “Other” category. The legend displays the color coding of genera along with the phyla to which these taxa belong (ie, Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria). Subjects A to D were treated with intranasal steroids, while subject E was treated with topical mupirocin. Pre: pretreatment time points. Intra: intratreatment time points. Post: posttreatment time points.

Figure 2.

Principal coordinates analysis (PCA). PCA was performed on species-level data for all subjects and time points. PC1, PC2, and PC3 accounted for 21.1%, 11.0%, and 10.3% of the overall variance, respectively. (a) Plots of samples along principal components axes 1 and 2 for all subjects/time points together along with separate plots for each individual. Subjects are distinguished by different symbol shapes, while time points are color coded by treatment phase (pre-, intra-, and posttreatment) and marked by time of sampling, in weeks (missing time points represents samples from which 16S rRNA gene PCR was not successful). (b) Correlations between PC1, PC2, and PC3 scores and most abundant bacterial species/genera. The heat map is color coded by Spearman correlation coefficient (rho), while P values are indicated by symbols: *P < .05. **P < .01. ***P < .001. PC1: principal coordinates axis 1; PC2: principal coordinates axis 2.

Figure 3.

Temporal variation in microbial diversity. These panels display the relative abundances of select bacterial genera (the 5 most highly abundant) and alpha-diversity indices across the study. Samples obtained at weeks 1 and 2 were pretreatment, those collected at weeks 3 to 6 were during treatment (indicated by shaded box), while those collected at weeks 7 and 8 were posttreatment. Subjects A to D were treated with intranasal steroids, while subject E was treated with topical mupirocin.

Figure 4.

Microbiome perturbation by host or external stressors can lead to a variable extent of disturbance in which return to a healthy baseline may occur (resilience). Reprinted from Vickery and Ramakrishnan with permission from Elsevier.