The effect of the microbiome on nasal epithelial barrier function in chronic rhinosinusitis
Chronic rhinosinusitis (CRS) is characterized by mucosal inflammation in the nasal cavity and the paranasal sinuses and effects approximately 11% of the European population. CRS is generally devided into two phenotypes depending on the presence or absence of nasal polyps, namely CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Despite the available treatment strategies, up to 40% of CRS patients remain uncontrolled even after surgery. As such there is an urgent need to identify endotypes of CRS to develop patient's tailored strategies.
Recently, a defective epithelial barrier, as a result of decreased tight junction (TJ) function, has been found in CRS. TJs are intercellular junctions that play an important role in maintaining an intact epithelial barrier and protect the human body from penetration of pathogens and allergens. Hence, restoring/preserving epithelial barrier function migth play a key role in the treatment of CRS.
Additionally, a dysregulated microbiome is also found in the etiology of CRS. Variou pathogenic bacteria have been associated with the pathology of CRS and can disrupt airway epithelial barrier integrity. However, microorganism can also induce beneficial effects to the host. These bacteria are called probiotics and can provide health benefits to the host when they are administered in adequate amounts. Traditionally, lactobacilli have been used as probiotics and various studies have shown that lactobacilli are normal inhibitants of the healthy upper respiratory tract. However, evidence of the regulatory properties of lactobacilli on airway epithelial cells is limited. Lactobacilli can modulate host immune responses by interacting with pattern recognition receptors, such as Toll-like receptors, present on nasal epithelial barrier.
In this PhD project, the microbiome in CRS patients is studied in relation to CRS pheno- and endotypes. Furthermore, the effect of Lactobacillus casei AMB-R2 on epithelial cells is investigated in healthy controls and patients with CRSwNP. Additionally, the potential beneficial effects of this species on barrier function are exerted through activation of TLR2 signaling in CRSwNP.