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

Abstract

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.

Bacterial community collapse: a meta‐analysis of the sinonasal microbiota in chronic rhinosinusitis

“…This lack of understanding is due to many factors, including small sample sizes, inadequate stratification of cohorts, insufficient taxonomic resolution of gene-targeted sequencing data and a restricted focus on the presence/ absence of microbes (community diversity) rather than community interaction and function. Additionally, much of the bacterial research in this field is limited to culturebased approaches which may not capture the extensive community diversity within the sinonasal cavity (Joss et al, 2015;Hoggard et al, 2017).…”

Detection of bacteria by 16S rRNA PCR and sequencing in culture‐negative chronic rhinosinusitis

“…Such data from culture‐negative samples will help the clinician plan further management, prognosticate the disease severity, and predict the possibility of recurrence. The need for more culture‐independent studies was recently pointed out by Hoggard et al This article contributes to our understanding of the involvement of bacteria in culture‐negative cases.…”

“…Current studies on the association between CRS and bacteria are based on conventional microbiological culture techniques . However, there are chances of the culture being negative due to the use of empirical antibiotics, improper handling and transport of the samples in the absence of transport medium, slower‐growing organisms that are outcompeted for a limited range of nutrient sources, and organisms that may be viable but nonculturable or difficult to culture . This study for the first time attempts to understand the involvement of bacteria in culture‐negative cases of CRS.…”

“…6,7 However, there are chances of the culture being negative due to the use of empirical antibiotics, improper handling and transport of the samples in the absence of transport medium, slower-growing organisms that are outcompeted for a limited range of nutrient sources, and organisms that may be viable but nonculturable or difficult to culture. 8 This study for the first time attempts to understand the involvement of bacteria in culture-negative cases of CRS. The results presented show that even culture-negative samples harbor bacteria, but the failure of conventional culture may be because of the low number of viable bacteria due to antibiotic treatment.…”

Is chronic rhinosinusitis an infectious disease? Insights from a microbiota meta‐analysis

“…() presented another way to provide clarity. After a thorough CRS literature survey (Hoggard et al ., ), these authors retrieved raw 16S rRNA gene sequence data from sinus microbiomes of CRS and associated controls and reanalysed the data. Such an approach has two advantages: first, it increases the total sample size up to 170 CRS patients and 79 controls and second, by using a uniform bioinformatic pipeline, a better comparison of data can be achieved compared to conventional meta‐analysis of published data.…”