Role of the microbiome in chronic sinus, oral and ear disease

Currently researched by Brett Wagner mackenzie, Anna Vesty, Michael Hoggard, Christian Lux & Jesse Baker

 

In collaboration with a team of ENT surgeons working under Prof. Richard Douglas (Auckland District Health Board & Department of Surgery, University of Auckland) and microbiologist Dr Kristi Biswas, we are investigating the microbiome in chronic sinus, oral and ear disease.  Our major focus is on chronic rhinosinusitis (CRS), a miserable condition which affects ~5% of the population and places a substantial burden on the healthcare system (direct healthcare costs associated with CRS cost billions of dollars each year in the USA alone).  While a microbial involvement in CRS has long been suspected, the aetiology of this condition remains unknown.  At this stage it is not even clear whether there is a bacterial, fungal or viral origin, or perhaps none of these, with CRS possibly representing an immune-based inflammatory condition with microbes playing a secondary role.  Rather than a specific, single pathogen being implicated, recent data from our group and others suggest that CRS may be associated with a breakdown, or dysbiosis, of the overall microbial community within the sinonasal cavity.  Conceivably, this could even be exacerbated by current treatment regimens which often include antibiotics.  We are employing traditional cultivation and modern molecular biology techniques (including shotgun metagenomics and 16S rRNA gene amplicon sequencing) to determine the role of the sinonasal microbiome in CRS.  Our PhD student Mike Hoggard recently published the most comprehensive review to date on the microbiology of CRS (Hoggard et al., 2017; Clinical Microbiology Reviews 30: 321-348).

 

One limitation of the CRS field to date has been the difficulty associated with obtaining a sufficient number of samples to allow us to detect a signal of the disease against a background of very high inter-individual variability.  Our data suggest that as much as 37% of variation in microbiota composition is due to differences between individual patients, while disease status (i.e. CRS vs healthy) accounts for only about 4%!  In a recent study we therefore conducted a meta-analysis of the publicly available 16S rRNA gene sequences from CRS studies (11 in total), which greatly increased the numbers of samples to work with and allowed us to identify potential “gatekeeper” bacteria which appear to be central to the functioning of a healthy sinonasal microbiota.  Check out the paper by Wagner Mackenzie et al. (2017) and the related Highlight article by Harald Brüssow (2017).

Wagner Mackenzie et al. (2017) Bacterial community collapse: a meta-analysis of the sinonasal microbiota in chronic rhinosinusitis. Environmental Microbiology 19: 381-392.

Brüssow, H. (2017) Is chronic rhinosinusitis an infectious disease? Insights from a microbiota meta-analysis. Environmental Microbiology 19: 1359-1362.

 

Figure:  16S rRNA gene-based bacterial community structure in 6 nasal sites from each of 9 individuals with CRS and 6 healthy control individuals, at (A) phylum and (B) genus level.  Note the dominance of the genus  Corynebacterium  in many individuals with and without CRS.  Modified from Fig. 1 in Biswas  et al.  (2015)  Frontiers in Microbiology  6: 134.   

Figure: 16S rRNA gene-based bacterial community structure in 6 nasal sites from each of 9 individuals with CRS and 6 healthy control individuals, at (A) phylum and (B) genus level.  Note the dominance of the genus Corynebacterium in many individuals with and without CRS.  Modified from Fig. 1 in Biswas et al. (2015) Frontiers in Microbiology 6: 134.

 

In addition to our studies of CRS and the nose, we also have an ongoing research project examining the oral microbiome in patients undergoing radiotherapy for head and neck cancers.  This research is carried out by Anna Vesty together with oral surgeon Dr Kim Gear, and seeks to elucidate the implications of microbiome composition for the success of these cancer treatments.

 

Last but not least, we are applying the same techniques described above to the chronic ear condition, chronic suppurative otitis media (CSOM).  This research, led by otologist Dr Michel Neeff, led to the first detailed molecular description of the microbiome in CSOM, and current work is focussing on the immunology of this disease.  Exploring the interplay between the microbiome and the host immune response is a central part of our research on the ear, nose and throat.

 

A selection of our publications on these topics include:

 

CRSBiswas et al., 2015; Hoggard et al., 2017; Wagner Mackenzie et al., 2017; Hoggard et al., 2017 (the most comprehensive review to date of the microbiology of CRS).

Oral microbiomeVesty et al., 2017

CSOM (chronic ear disease)Neeff et al., 2016

 

We gratefully acknowledge the generous funding support for the work described above from the Garnett Passe & Rodney Williams Memorial Foundation, Maurice & Phyllis Paykel Trust, University of Auckland and the A+ Trust.