Lacticaseibacillus casei AMBR2 modulates the epithelial barrier function and immune response in a donor-derived nasal microbiota manner.

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.