53 The Importance of Secretory IgA on Trans-Epithelial Transport of Commensal Bacteria and its Consequences on Neonatal Immune Development: Preclinical Assessment

Background and aims Secretory IgA (SIgA) naturally binds to commensal bacteria and is able to cross back through the intestinal epithelium to promote immune responses. The aim of the present work was to investigate the contribution of SIgA on the trans-epithelial transport of commensal bacteria, such as probiotics, and its consequences on neonatal immune development as such process may also occur with SIgA originating from breast milk. Methods Fluorescent bacteria alone or associated with SIgA as immune complexes (IC) were administered into intestinal loops containing one Peyer’s patch (PP) in SPF or germ-free mice. Fate of bacteria within PP over time was analyzed by confocal microscopy. After day 7 of life, germ-free mouse neonates were conventionalized to induce natural neonatal gut colonization and supplemented up to weaning with either placebo, probiotics or IC. Immune maturation was then assessed by measuring mucosal IgA production (ELISPOTs) in PPs. Results Natural entry of commensal bacteria into PP was speeded up when administered in the form of IC. In germ-free mice, lacking endogenous SIgA, a very low level of trans-epithelial transport of commensal bacteria was observed, which was restored with IC. While early-life supplementation with probiotics alone significantly enhanced occurrence of IgA producing cells in PPs of pups as compared to controls, IC feeding significantly further increased it. Conclusions SIgA-mediated entry of commensal bacteria in PPs represents a mechanism ensuring the continuous dialogue between the host and its microbiota, particularly relevant for neonatal immune development.