Animal models for inflammatory mucosal disease and their potential for studying the microbiome in chronic rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is a morbid condition of the paranasal sinuses which severely impairs patients' quality of life. CRS represents one of the leading diseases that are responsible for antibiotic prescriptions. However, there is little evidence to support the efficacy of antibiotics in CRS. Due to the highly heterogeneous nature of CRS determining the underlying etiology is challenging. The mucosal microbiome has been hypothesised to play a role in the pathophysiology of CRS.Several attempts to establish a representative model of CRS have been made to help determine the pathogenesis of this condition. This review summarises the current literature on model systems for inflammatory sinus disease. Fourteen different studies are discussed, including mouse, rabbit and sheep as model organisms. A detailed description of the methods for model development and examples for their application are provided. Focus is put on animal models that should be suitable for studying the sinonasal microbiome in CRS. To date, only two studies sought to employ their model for microbiome analysis. Other models are included for which there is currently no microbiome information, however they are of potential use in this regard and we thus discuss their suitability.This review identifies a need for further employment of animal models of CRS for microbiome research. Recently, a rabbit model of CRS featuring several qualities that make it particularly suitable for microbiological research has been described. This model system represents a further advance of translational research in the field of CRS.

Lactic acid bacteria as probiotics for the nose?

“…In particular for CRS, the available animal models do not represent all aspects of the pathology of CRS relevant for microbiome research. Development of mouse models is especially challenging due to significant differences within their respiratory system, including sinonasal anatomy that is not representative for humans (Wenzel and Holgate, 2006;Al-Sayed et al, 2017;Kolanjiyil et al, 2019;Lux et al, 2019). In addition, mice are obligated nose-only breathers, whereas humans breathe via their nose and/ or mouth (Kolanjiyil et al, 2019).…”

“…It should be noted that this comparison was mainly done at the phylum and order level and no other studies have investigated the similarities of the rabbit and human respiratory tract microbiota. Some higher animal models such as pigs and sheep can be considered as well, as they show more anatomical URT similarities with humans (Lux et al, 2019). The paranasal sinuses of pigs are for instance largely similar to humans, with two main complexes, that is, maxillary and frontal sinuses, and the sphenoid and lacrimal sinuses as smaller sinuses, making them a feasible model for sinonasal research (Wang et al, 2013).…”

Unilateral Intervention in the Sinuses of Rabbits Induces Bilateral Inflammatory and Microbial Changes

“…CRS generally presents bilaterally and if the potential for inflammation to spread locally is also present in human patients, it could explain some of the clinical observations. One of the major advantages of creating a unilateral model is that the contralateral side can be used as a control ( Lux et al., 2019 ). Considering these findings, however, we advise careful monitoring of the mucosa and microbiota of the contralateral sinus and recommend that the contralateral sinus may not be used as a true negative control.…”

“…Animal models can help overcome many of these issues and several species have been used successfully to study the pathophysiology of CRS ( London and Lane, 2016 ; Shin, 2016 ; Lux et al., 2019 ). Animal models are particularly helpful when studying the efficacy of novel treatments ( Chiu et al., 2007 ; Tamashiro et al., 2009 ; Jia et al., 2017 ; Yoruk et al., 2017 ).…”

“…Animal models are particularly helpful when studying the efficacy of novel treatments ( Chiu et al., 2007 ; Tamashiro et al., 2009 ; Jia et al., 2017 ; Yoruk et al., 2017 ). In a recent CRS-focused review of animal models for the study of chronic mucosal inflammation, rabbits were found to be a particularly suitable model in regards to animal handling and features of sinus anatomy and physiologic characteristics ( Lux et al., 2019 ). Methods for inducing inflammation of the sinus mucosa include microbial inoculation ( Abreu et al., 2012 ; Jia et al., 2014 ), administration of inflammatory agents ( Gocea et al., 2013 ; Khalmuratova et al., 2016 ) and mechanical obstruction of the sinus ostia ( Ha et al., 2007 ; Migliavacca et al., 2014 ; Cho et al., 2018 ), or a combination of these ( Boase et al., 2011 ).…”