Relationship of the Middle Ear Effusion Microbiome to Secretory Mucin Production in Pediatric Patients With Chronic Otitis Media.

BACKGROUND: Acute otitis media, an infection of the middle ear, can become chronic after multiple episodes. Microbial influence on chronic otitis media remains unclear. It has been reported that mucin glycoproteins are required for middle ear immune defense against pathogens. We aim to characterize the middle ear effusion (MEE) microbiome using high-throughput sequencing and assess potential associations in microbiome diversity with the presence of the secretory mucins MUC5B and MUC5AC. We hypothesize that MEEs containing MUC5B will exhibit a microbiome largely devoid of typical acute otitis media bacteria. METHODS: Fifty-five MEEs from children undergoing myringotomy at Children's National Health System were recovered. Mucin was semiquantitatively determined through Western blot analysis. DNA was subjected to 16S rRNA amplicon sequencing using the Illumina MiSeq platform. Raw data were processed in mothur (SILVA reference database). Alpha- and beta-diversity metrics were determined. Abundance differences between sample groups were estimated. RESULTS: MUC5B was present in 94.5% and MUC5AC in 65.5% of MEEs. Sequencing revealed 39 genera with a relative abundance ≥0.1%. Haemophilus (22.54%), Moraxella (11.11%) and Turicella (7.84%) were the most abundant. Turicella and Pseudomonas proportions were greater in patients older than 24 months of age. In patients with hearing loss, Haemophilus was more abundant, while Turicella and Actinobacteria were less abundant. Haemophilus was also more abundant in samples containing both secretory mucins. CONCLUSIONS: The microbiome of MEEs from children with chronic otitis media differs according to specific clinical features, such as mucin content, age and presence of hearing loss. These associations provide novel pathophysiologic insights across the spectrum of otitis media progression.

Younger patients with COME are more likely to have mucoid middle ear fluid containing mucin MUC5B.

BACKGROUND: Chronic otitis media (COM) is one of the most common childhood diseases. Its pathophysiology is complex and multifactorial. The role of specific mucin glycoprotein subtypes in OM is only recently being elucidated. OBJECTIVE: To determine the relationship between middle ear fluid mucins and clinical variables of patients needing tympanostomy tubes (TT). METHODS: Middle ear effusions (MEE) from children receiving TT were collected over a 2-year period. Western blot characterization of mucins MUC5B and MUC5AC along with chart review of age, gender, effusion viscosity, hearing loss >30 dB, history of allergies, and/or respiratory disease were performed. RESULTS: MEE samples from 58 patients were available for analysis. Overall, MUC5B was significantly more often detected in middle ear fluid relative to MUC5AC (90% vs. 51%, p = 0.005). MUC5B presence was statistically associated with mucoid effusions relative to serous effusions (100% vs. 57%, p = 0.0064), MUC5AC presence was not significantly different in mucoid and serous fluid (55.1% vs. 37.5%, p = 0.447). Patients younger than 48 months were more likely to present with mucoid effusion, compared to those older than 48 months of age (p = 0.038). Finally, patients with effusions positive for MUC5B were younger than those with effusions negative for MUC5B (35.1 vs. 76 months, p = 0.045). No other variables correlated to either effusion viscosity or specific mucin content. CONCLUSION: Patients younger in age needing TT placement are more likely to present with mucoid effusions, predominantly containing MUC5B mucin. As such, we postulate a distinct pathophysiology for mucoid and serous effusions across ages in children with COM.