Case-Control Microbiome Study of Chronic Otitis Media with Effusion in Children Points at Streptococcus salivarius as a Pathobiont-Inhibiting Species

Abstract

Chronic otitis media with effusion (OME) has been associated with a shift in microbiome composition and microbial interaction in the upper respiratory tract (URT). While most studies have focused on potential pathogens, this study aimed to find bacteria that could be protective against OME through a case-control microbiome study and characterization of isolates from healthy subjects. The URT and ear microbiome profiles of 70 chronic OME patients and 53 controls were compared by 16S rRNA amplicon sequencing. Haemophilus influenzae was the most frequent classic middle ear pathobiont. However, other taxa, especially Alloiococcus otitis, were also frequently detected in the ear canal of OME patients. Streptococci of the salivarius group and Acinetobacter lwoffii were more abundant in the nasopharynx of healthy controls than in OME patients. In addition to the microbiome analysis, 142 taxa were isolated from healthy individuals, and 79 isolates of 13 different Streptococcus species were tested for their pathobiont-inhibiting potential. Of these, Streptococcus salivarius isolates showed a superior capacity to inhibit the growth of H. influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, A. otitis, and Corynebacterium otitidis. S. salivarius strains thus show potential as a probiotic for prevention or treatment of OME based on their overrepresentation in the healthy nasopharynx and their ability to inhibit the growth of respiratory pathobionts. (This study has been registered at ClinicalTrials.gov under registration no. NCT03109496.) IMPORTANCE The majority of probiotics marketed today target gastrointestinal health. This study searched for bacteria native to the human upper respiratory tract, with a beneficial potential for respiratory and middle ear health. Comparison of the microbiomes of children with chronic otitis media with effusion (OME) and of healthy controls identified Streptococcus salivarius as a health-associated and prevalent inhabitant of the human nasopharynx. However, beneficial potential should be assessed at strain level. Here, we also isolated specific S. salivarius strains from the healthy individuals in our study. These isolates showed a beneficial safety profile and efficacy potential to inhibit OME pathogens in vitro. These properties will now have to be evaluated and confirmed in human clinical studies.

Identification of the Bacterial Pathogens in Children with Otitis Media: A Study in the Northwestern Portuguese District of Braga

“…Most of the samples analyzed are from OME cases (85.71%). Therefore, the identification of H. influenzae as the most prevalent pathogen in the MEF agrees with other studies that report H. influenzae as the predominant pathogen in OME [8,14,35]. However, the reported prevalence rates are highly variable due to different health care programs, particularly vaccination, in various geographical locations [36].…”

The microbiota in respiratory tract infections: from association to intervention

“…Furthermore, probiotic treatment with Streptococcus salivarius has been explored for children suffering from chronic otitis media. S. salivarius can inhibit growth of most pathogens known to cause otitis media infections, among others including S. pneumoniae, H. influenzae, M. catarrhalis [37,38]. However, it has not yet been shown that D. pigrum supplementation, in isolation or combined with Corynebacterium, can also effectuate short-term or long-term clinical improvement.…”

Microbiota Associated With Cholesteatoma Tissue in Chronic Suppurative Otitis Media

“…Corynebacterium is also commonly identified in COM but is typically viewed as a commensal, even potentially otoprotective in acute OM ( Lappan et al., 2018 ; Jorissen et al., 2021 ). In contrast, Porphyromonas , Fusobacterium and Campylobacter ( Figure 1 , Figure 3 ) are less commonly isolated from patients with COM or cholesteatoma ( Brook, 1995 ; Yusuf et al., 2015 ).…”