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

Jennifer Jörissen,Stijn Wittouck,Liesbet Van Heirstraeten,Ine Wouters,Heidi Theeten,Olivier M Vanderveken,Ilke De Boeck,Marianne F L Van Den Broek,Paul Van De Heyning,Sarah Lebeer,Vedat Topsakal,Wannes Van Beeck,Surbi Malhotra-Kumar,Pierre Van Damme,Vincent Van Rompaey,An Boudewyns,Paul D Cotter

doi:10.1128/msystems.00056-21

Jennifer Jörissen, Stijn Wittouck + Show 15 more

Open Access

https://doi.org/10.1128/msystems.00056-21

Copy DOI

Journal: mSystems	Publication Date: Apr 27, 2021
Citations: 18	License type: CC BY 4.0

Affiliation: University of Antwerp, Antwerp University Hospital

Abstract

ABSTRACTChronic 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.

Highlights

IMPORTANCE The majority of probiotics marketed today target gastrointestinal health
A nasal spray containing 2 Streptococcus sanguinis strains, 1 Streptococcus mitis strain, and 1 Streptococcus oralis strain isolated from the opening of the Eustachian tube of healthy children reduced the rate of acute otitis media (AOM) and otitis media with effusion (OME) when participants were pretreated with antibiotics [26], but not when antibiotic treatment was omitted [27]
70 4.38 6 2.42 41 AN, NP, Ad, Ad, ME, ECa guide the subsequent cultivation approach and phenotyping, focusing on the ability of upper respiratory tract (URT) isolates from healthy individuals to inhibit the growth of classic middle ear pathobionts, as well as on underexplored potential OME-associated pathobionts that were identified in the microbiome comparison

Summary

Introduction

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. Bacteria traditionally isolated from OME middle ear effusion are nontypeable (unencapsulated) Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, which typically inhabit the URT [3] In addition to these classic otopathogens, multiple 16S rRNA gene sequencing studies of OME middle ear effusion reported high levels of Alloiococcus otitis, Corynebacterium otitidis (formerly Turicella otitidis [4]), Pseudomonas spp., and Staphylococcus spp. A recent bacterial intervention study using Ligilactobacillus salivarius PS7 isolated from human milk reported reductions in the risk of experiencing at least one episode of AOM by 49% and in the length of AOM episodes from 6 to 4 days in otitis-prone children It is unclear whether this effect was achieved through local or systemic mechanisms, as the formulation was not described, and colonization of the URT was not measured [29]. 70 4.38 6 2.42 41 AN, NP, Ad, Ad, ME, ECa guide the subsequent cultivation approach and phenotyping, focusing on the ability of URT isolates from healthy individuals to inhibit the growth of classic middle ear pathobionts, as well as on underexplored potential OME-associated pathobionts that were identified in the microbiome comparison

Objectives

Methods

Results

Discussion

Conclusion