A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera

Abstract

BackgroundRecurrent acute otitis media (rAOM, recurrent ear infection) is a common childhood disease caused by bacteria termed otopathogens, for which current treatments have limited effectiveness. Generic probiotic therapies have shown promise, but seem to lack specificity. We hypothesised that healthy children with no history of AOM carry protective commensal bacteria that could be translated into a specific probiotic therapy to break the cycle of re-infection. We characterised the nasopharyngeal microbiome of these children (controls) in comparison to children with rAOM (cases) to identify potentially protective bacteria. As some children with rAOM do not appear to carry any of the known otopathogens, we also hypothesised that characterisation of the middle ear microbiome could identify novel otopathogens, which may also guide the development of more effective therapies.ResultsMiddle ear fluids, middle ear rinses and ear canal swabs from the cases and nasopharyngeal swabs from both groups underwent 16S rRNA gene sequencing. The nasopharyngeal microbiomes of cases and controls were distinct. We observed a significantly higher abundance of Corynebacterium and Dolosigranulum in the nasopharynx of controls. Alloiococcus, Staphylococcus and Turicella were abundant in the middle ear and ear canal of cases, but were uncommon in the nasopharynx of both groups. Gemella and Neisseria were characteristic of the case nasopharynx, but were not prevalent in the middle ear.ConclusionsCorynebacterium and Dolosigranulum are characteristic of a healthy nasopharyngeal microbiome. Alloiococcus, Staphylococcus and Turicella are possible novel otopathogens, though their rarity in the nasopharynx and prevalence in the ear canal means that their role as normal aural flora cannot be ruled out. Gemella and Neisseria are unlikely to be novel otopathogens as they do not appear to colonise the middle ear in children with rAOM.Electronic supplementary materialThe online version of this article (10.1186/s12866-018-1154-3) contains supplementary material, which is available to authorized users.

Reviewing the Pathogenic Potential of the Otitis-Associated Bacteria Alloiococcus otitidis and Turicella otitidis

“…We recently took a similar approach, undertaking 16S rRNA amplicon sequencing on EAC and MEF samples from children with rAOM (Lappan et al, 2018). We observed A. otitidis and T. otitidis as dominant organisms in both sites in a cohort where the majority of children had no known current tympanic membrane perforations or previous grommets.…”

“…Placed within the Carnobacteriaceae family, it is the only species in its genus and is most closely related to Dolosigranulum by 16S rRNA sequence homology (Vos et al, 2009). Dolosigranulum is a nasopharyngeal commensal of relevance to OM, and their similarity leads to misclassification in 16S rRNA gene surveys using older taxonomic databases (Lappan et al, 2018). A. otitidis strains have been characterized as resistant to trimethoprim-sulfamethoxazole and macrolides, and susceptible or intermediately resistant to penicillin and ampicillin (Bosley et al, 1995;Ashhurst-Smith et al, 2007;Marsh et al, 2012), though they are β-lactamase negative (Bosley et al, 1995).…”

“…Like A. otitidis, T. otitidis is the only member of its genus and was placed in the Corynebacteriaceae family with its closest relative, Corynebacterium (Goodfellow et al, 2012); though it has recently been proposed that T. otitidis is a true member of the Corynebacterium genus (Baek et al, 2018). Like A. otitidis, T. otitidis' closest relative is also a nasopharyngeal commensal, and Corynebacterium and Dolosigranulum commonly co-occur in healthy children (Biesbroek et al, 2014;Lappan et al, 2018). T. otitidis is similarly misclassified as Corynebacterium in at least one ribosomal taxonomic database (Lappan et al, 2018).…”

“…Like A. otitidis, T. otitidis' closest relative is also a nasopharyngeal commensal, and Corynebacterium and Dolosigranulum commonly co-occur in healthy children (Biesbroek et al, 2014;Lappan et al, 2018). T. otitidis is similarly misclassified as Corynebacterium in at least one ribosomal taxonomic database (Lappan et al, 2018). T. otitidisis sensitive to tetracyclines and amoxicillin, but is resistant to sulfamethoxazole and co-trimoxazole (Troxler et al, 2001) and some strains have developed mutations conferring macrolide resistance (Gómez-Garcés et al, 2004;Boumghar-Bourtchai et al, 2009).…”

“…In the microbiota of MEF, Alloiococcus appears to be one of the dominant genera (Jervis- Bardy et al, 2015;Chan et al, 2016Chan et al, , 2017bBoers et al, 2018;Lappan et al, 2018;Val et al, 2018;Johnston et al, 2019). Turicella is less often reported, but has been identified as a member of the MEF microbiota in 8 of the 12 MEF microbiota studies reported in Table 3 (Jervis- Bardy et al, 2015;Krueger et al, 2017;Minami et al, 2017;Sillanpää et al, 2017;Boers et al, 2018;Lappan et al, 2018;Val et al, 2018;Johnston et al, 2019). However, due to the compositional nature of microbiome data it remains difficult to interpret which organisms are more abundant than others.…”