Abstract
BackgroundThe first exposure to microorganisms at mucosal surfaces is critical for immune maturation and gut health. Facultative anaerobic bacteria are the first to colonise the infant gut, and the impact of these bacteria on intestinal epithelial cells (IEC) may be determinant for how the immune system subsequently tolerates gut bacteria.ResultsTo mirror the influence of the very first bacterial stimuli on infant IEC, we isolated IEC from mouse foetuses at gestational day 19 and from germfree neonates. IEC were stimulated with gut-derived bacteria, Gram-negative Escherichia coli Nissle and Gram-positive Lactobacillus acidophilus NCFM, and expression of genes important for immune regulation was measured together with cytokine production. E. coli Nissle and L. acidophilus NCFM strongly induced chemokines and cytokines, but with different kinetics, and only E. coli Nissle induced down-regulation of Toll-like receptor 4 and up-regulation of Toll-like receptor 2. The sensitivity to stimulation was similar before and after birth in germ-free IEC, although Toll-like receptor 2 expression was higher before birth than immediately after.ConclusionsIn conclusion, IEC isolated before gut colonisation occurs at birth, are highly responsive to stimulation with gut commensals, with L. acidophilus NCFM inducing a slower, but more sustained response than E. coli Nissle. E. coli may induce intestinal tolerance through very rapid up-regulation of chemokine and cytokine genes and down-regulation of Toll-like receptor 4, while regulating also responsiveness to Gram-positive bacteria.
Highlights
The first exposure to microorganisms at mucosal surfaces is critical for immune maturation and gut health
E. coli was most potent in up-regulating Cxcl1, Cxcl2, Ccl2 and Ccl3 encoding keratinocyte-derived chemokine (KC), macrophage-inflammatory protein (MIP)-2, monocyte chemoattractant protein (MCP)-1 and MIP-1a respectively
Chemokine expression induced by E. coli did not increase from 2 to 4 h, whereas induction of Ccl3 by L. acidophilus reached transcription levels induced by E. coli only at 4 h
Summary
The first exposure to microorganisms at mucosal surfaces is critical for immune maturation and gut health. Colonisation at birth by facultative anaerobes, such as enterobacteria, coliforms, lactobacilli and streptococci, creates a reducing environment during the first week of life enabling colonisation by strict anaerobes including bifidobacteria, bacteroides, clostridia and eubacteria [3]. This microbial colonisation contributes to recruitment of immune cells to the GI tract and may be a major contributor to establishment of the systemic immune system [4,5]. Colonisation in early infancy is crucial in relation to the final composition of the permanent microbiota in adults and in inducing intestinal and immunological maturation
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