Michael Hoggard

The nasal microbiota in health and disease: variation within and between subjects

Chronic rhinosinusitis (CRS) affects approximately 5% of the adult population in Western societies and severely reduces the patient’s quality of life. The role of bacteria in the pathogenesis of this condition has not yet been established with certainty. However, recent reports of bacterial and fungal biofilms in CRS highlight a potential role for these microorganisms. In this study, 16S rRNA gene-targeted amplicon pyrosequencing and qPCR were used to determine the composition and abundance, respectively, of the sinus microbiota within 9 patients with CRS and 6 healthy individuals. Within-patient variability was also investigated by sampling from anterior nares, inferior turbinate, and middle meatus on each side of the sinuses. Our results indicate that more of the variation in bacterial composition can be explained by inter-personal differences, rather than sampling location or even disease status. In addition, bacterial community diversity was significantly lower in CRS samples compared to those from healthy subjects, whereas bacterial load was not associated with disease status. Although members of the genera Corynebacterium and Staphylococcus were prevalent in the majority of samples (including healthy subjects), the large amount of variation observed between individuals, particularly within the CRS cohort, suggests that an imbalance or dysbiosis in community structure could be the driving force behind the disease. Ultimately, understanding the causes of variation within the sinus microbiota may lead to more personalized treatment options for CRS.

Influence of environmental variation on symbiotic bacterial communities of two temperate sponges

Sponges are an important component of temperate subtidal marine ecosystems, with a range of important functional roles and extensive symbiotic relationships with microorganisms. However, much remains unknown about their relationships with these symbiotic microorganisms, and specifically, the role that these symbionts play in sponge physiology, feeding and adaptation to local environmental conditions. Changes in environmental factors may alter relationships between sponges and their symbionts, which could conceivably influence the abundance and distribution patterns of some temperate sponge species. Here, we analyzed the effect of transplantation of sponges between different habitats to test the effect of changes in environmental conditions on the stability of the bacterial communities in specimens of Tethya bergquistae and Ecionemia alata, based on pyrosequencing of amplified 16S rRNA genes. Bacterial communities differed markedly between the two host species. While some morphological changes were observed in transplanted sponges, transplantation had little overall effect on sponge-associated bacterial communities at either phylum or 97%-OTU level. Our results show the importance of host species and also the stability of sponge-associated bacterial communities under environmental variation.

Bacterial community collapse: A meta-analysis of the sinonasal microbiota in chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a common, debilitating condition characterized by long-term inflammation of the nasal cavity and paranasal sinuses. The role of the sinonasal bacteria in CRS is unclear. We conducted a meta-analysis combining and reanalysing published bacterial 16S rRNA sequence data to explore differences in sinonasal bacterial community composition and predicted function between healthy and CRS affected subjects. The results identify the most abundant bacteria across all subjects as Staphylococcus, Propionibacterium, Corynebacterium, Streptococcus and an unclassified lineage of Actinobacteria. The meta-analysis results suggest that the bacterial community associated with CRS patients is dysbiotic and ecological networks fostering healthy communities are fragmented. Increased dispersion of bacterial communities, significantly lower bacterial diversity, and increased abundance of members of the genus Corynebacterium are associated with CRS. Increased relative abundance and diversity of other members belonging to the phylum Actinobacteria and members from the genera Propionibacterium differentiated healthy sinuses from those that were chronically inflamed. Removal of Burkholderia and Propionibacterium phylotypes from the healthy community dataset was correlated with a significant increase in network fragmentation. This meta-analysis highlights the potential importance of the genera Burkholderia and Propionibacterium as gatekeepers, whose presence may be important in maintaining a stable sinonasal bacterial community.

Evidence of microbiota dysbiosis in chronic rhinosinusitis

Despite considerable research, the pathogenesis of chronic rhinosinusitis (CRS) remains poorly understood. Potential microbial roles in the etiology or progression of CRS have long been hypothesized, yet few specific associations have been identified. In this study we investigate associations between patterns in resident bacterial communities and clinical variants of CRS.

Paired analysis of the microbiota of surface mucus and whole-tissue specimens in patients with chronic rhinosinusitis.

The role of bacteria in the pathogenesis of chronic rhinosinusitis (CRS) remains uncertain. Recent evidence suggests that bacteria are able to establish microcolonies within the underlying mucosa. However, to date there has been no systematic comparison of bacterial community composition and diversity in the surface mucosa with that of the underlying tissue.

In four shallow and mesophotic tropical reef sponges from Guam the microbial community largely depends on host identity

Sponges (phylum Porifera) are important members of almost all aquatic ecosystems, and are renowned for hosting often dense and diverse microbial communities. While the specificity of the sponge microbiota seems to be closely related to host phylogeny, the environmental factors that could shape differences within local sponge-specific communities remain less understood. On tropical coral reefs, sponge habitats can span from shallow areas to deeper, mesophotic sites. These habitats differ in terms of environmental factors such as light, temperature, and food availability, as well as anthropogenic impact. In order to study the host specificity and potential influence of varying habitats on the sponge microbiota within a local area, four tropical reef sponges, Rhabdastrella globostellata, Callyspongia sp., Rhaphoxya sp., and Acanthella cavernosa, were collected from exposed shallow reef slopes and a deep reef drop-off. Based on 16S rRNA gene pyrosequencing profiles, beta diversity analyses revealed that each sponge species possessed a specific microbiota that was significantly different to those of the other species and exhibited attributes that are characteristic of high- and/or low-microbial-abundance sponges. These findings emphasize the influence of host identity on the associated microbiota. Dominant sponge- and seawater-associated bacterial phyla were Chloroflexi, Cyanobacteria, and Proteobacteria. Comparison of individual sponge taxa and seawater samples between shallow and deep reef sites revealed no significant variation in alpha diversity estimates, while differences in microbial beta diversity (variation in community composition) were significant for Callyspongia sp. sponges and seawater samples. Overall, the sponge-associated microbiota is significantly shaped by host identity across all samples, while the effect of habitat differentiation seems to be less predominant in tropical reef sponges.

Chronic Rhinosinusitis and the Evolving Understanding of Microbial Ecology in Chronic Inflammatory Mucosal Disease

SUMMARY Chronic rhinosinusitis (CRS) encompasses a heterogeneous group of debilitating chronic inflammatory sinonasal diseases. Despite considerable research, the etiology of CRS remains poorly understood, and debate on potential roles of microbial communities is unresolved. Modern culture-independent (molecular) techniques have vastly improved our understanding of the microbiology of the human body. Recent studies that better capture the full complexity of the microbial communities associated with CRS reintroduce the possible importance of the microbiota either as a direct driver of disease or as being potentially involved in its exacerbation. This review presents a comprehensive discussion of the current understanding of bacterial, fungal, and viral associations with CRS, with a specific focus on the transition to the new perspective offered in recent years by modern technology in microbiological research. Clinical implications of this new perspective, including the role of antimicrobials, are discussed in depth. While principally framed within the context of CRS, this discussion also provides an analogue for reframing our understanding of many similarly complex and poorly understood chronic inflammatory diseases for which roles of microbes have been suggested but specific mechanisms of disease remain unclear. Finally, further technological advancements on the horizon, and current pressing questions for CRS microbiological research, are considered.

Changes in the bacterial microbiome of patients with chronic rhinosinusitis after endoscopic sinus surgery

Endoscopic sinus surgery (ESS) improves symptoms for many chronic rhinosinusitis (CRS) patients by enlarging the size of sinus ostia, improving mucociliary clearance, and facilitating access for topical therapies. However, the effect of surgery on the sinonasal microbiota remains poorly understood. This study examined changes in bacterial communities in CRS patients before and after surgery.

Molecular Microbiological Profile of Chronic Suppurative Otitis Media

ABSTRACT Chronic suppurative otitis media (CSOM) presents with purulent otorrhea (ear discharge), is characterized by chronic inflammation of the middle ear and mastoid cavity, and contributes to a significant disease burden worldwide. Current antibiotic therapy is guided by swab culture results. In the absence of detailed molecular microbiology studies of CSOM patients, our current understanding of the microbiota of CSOM (and indeed of the healthy ear) remains incomplete. In this prospective study, 24 patients with CSOM were recruited, along with 22 healthy controls. Culture-based techniques and 16S rRNA gene amplicon sequencing were used to profile the bacterial community for each patient. Comparisons between patients with and without cholesteatoma in the middle ear and mastoid cavity were also made. A major finding was that the middle ear of many healthy controls was not sterile, which is contradictory to the results of previous studies. However, sequencing data showed that Staphylococcus aureus, along with a range of other Gram-positive and Gram-negative organisms, were present in all subgroups of CSOM and healthy controls. Large interpatient variability in the microbiota was observed within each subgroup of CSOM and controls, and there was no bacterial community “signature” which was characteristic of either health or disease. Comparisons of the culture results with the molecular data show that culture-based techniques underestimate the diversity of bacteria found within the ear. This study reports the first detailed examination of bacterial profiles of the ear in healthy controls and patients with CSOM.

Toll-like receptor activation by sino-nasal mucus in chronic rhinosinusitis.

BACKGROUND The sino-nasal disease chronic rhinosinusitis (CRS) is primarily an inflammatory condition that manifests in several ways. However, the aetiology of this complex disease is poorly understood. The aim of this study was to explore the association between toll-like receptor (TLR) activation, host immune response and sino-nasal mucus in healthy and diseased patients. METHODS The activation of TLR2/1 and TLR4 by sino-nasal mucus from 26 CRS patients and 10 healthy controls was measured. In addition, 7 inflammatory cytokines, bacterial community composition and bacterial abundance within the sino-nasal mucus were measured using molecular and diagnostic tools. RESULTS TLR activity was observed in 9/36 samples, including 2 healthy controls. There was a strong, positive correlation between members of the Gammaproteobacteria (Haemophilus, Enterobacter, Pseudomonas) and TLR2/1 and TLR4 activity. Bacterial abundance and cytokine (tumour necrosis factor) abundance were also positively correlated with TLR activity. CONCLUSIONS These findings suggest that a small proportion (20-30%) of individuals in each sub-group are more predisposed to TLR activity, which may be related to bacterial composition, diversity and abundance in the sinuses.