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Surgical interventions are often augmented by antibiotic resistance development and therefore, off-label treatment using the natural drug 1,8-Cineol was carried out. All COM patients underwent antibiotic therapy and middle ear surgery and developed antibiotic resistances. Microbiological investigations from the auditory canal and stool samples were performed in correlation with the clinical course. Therapy of COM patients with 1,8-Cineol revealed a clear reduction of inflammatory microbes <jats:italic>P. aeruginosa<\/jats:italic> and <jats:italic>Proteus mirabilis<\/jats:italic> in ear samples as well as intestinal <jats:italic>Prevotella copri<\/jats:italic>, which was associated with an improved clinical outcome in certain individuals. The present off-label study revealed manifold anti-inflammatory effects of the natural monoterpene 1,8-Cineol in Otitis media patients. 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