Highlights d Lactic acid bacteria are enriched in the healthy human nose and nasopharynx d Lactobacillus casei AMBR2 is functionally adapted to the upper respiratory tract d L. casei AMBR2 has antimicrobial and immunomodulatory properties d Live L. casei AMBR2 is safe for intranasal application in healthy humans

Highlights d Lactic acid bacteria are enriched in the healthy human nose and nasopharynx d Lactobacillus casei AMBR2 is functionally adapted to the upper respiratory tract d L. casei AMBR2 has antimicrobial and immunomodulatory properties d Live L. casei AMBR2 is safe for intranasal application in healthy humans

Live biotherapeutic products (LBP) are emerging as alternative treatment strategies for chronic rhinosinusitis. The selection of interesting candidate LBPs often involves model systems that do not include the polymicrobial background (i.e. the host microbiota) in which they will be introduced. Here, we performed a screening in a simplified model system of upper respiratory epithelium to assess the effect of nasal microbiota composition on the ability to attach and grow of a potential LBP, Lacticaseibacillus casei AMBR2, in this polymicrobial background. After selecting the most permissive and least permissive donor, L. casei AMBR2 colonisation in their respective polymicrobial backgrounds was assessed in more physiologically relevant model systems. We examined cytotoxicity, epithelial barrier function, and cytokine secretion, as well as bacterial cell density and phenotypic diversity in differentiated airway epithelium based models, with or without macrophage-like cells. L. casei AMBR2 could colonize in the presence of both selected donor microbiota and increased epithelial barrier resistance in presence of donor-derived nasal bacteria, as well as anti-inflammatory cytokine secretion in the presence of macrophage-like cells. This study highlights the potential of L. casei AMBR2 as LBP and the necessity to employ physiologically relevant model systems to investigate host–microbe interaction in LBP research.

Chronic rhinosinusitis (CRS) is a chronic inflammation of the mucosa of the nose and paranasal sinuses affecting approximately 11% of the adult population in Europe. Inadequate immune responses, as well as a dysbiosis of the sinonasal microbiota, have been put forward as aetiological factors of the disease. However, despite the prevalence of this disease, there is no consensus on the aetiology and mechanisms of pathogenesis of CRS. Further research requires in vitro models mimicking the healthy and diseased host environment along with the sinonasal microbiota. This review aims to provide an overview of CRS model systems and proposes in vitro modelling strategies to conduct mechanistic research in an ecological framework on the sinonasal microbiota and its interactions with the host in health and CRS.