Late-onset sepsis (LOS) is a highly consequential complication of preterm birth and is defined by a positive blood culture obtained after 72 h of age. The causative bacteria can be found in patients’ intestinal tracts days before dissemination, and cohort studies suggest reduced LOS risk in breastfed preterm infants through unknown mechanisms. Reduced concentrations of epidermal growth factor (EGF) of maternal origin within the intestinal tract of mice correlated to the translocation of a gut-resident human pathogenEscherichia coli, which spreads systemically and caused a rapid, fatal disease in pups. Translocation ofEscherichia coliwas associated with the formation of colonic goblet cell-associated antigen passages (GAPs), which translocate enteric bacteria across the intestinal epithelium. Thus, maternally derived EGF, and potentially other EGFR ligands, prevents dissemination of a gut-resident pathogen by inhibiting goblet cell-mediated bacterial translocation. Through manipulation of maternally derived EGF and alteration of the earliest gut defenses, we have developed an animal model of pathogen dissemination which recapitulates gut-origin neonatal LOS.
In healthy hosts the gut microbiota is restricted to gut tissues by several barriers some of which require MyD88-dependent innate immune sensor pathways. Nevertheless, some gut taxa have been reported to disseminate to systemic tissues. However, the extent to which this normally occurs during homeostasis in healthy organisms is still unknown. In this study, we recovered viable gut bacteria from systemic tissues of healthy wild type (WT) and MyD88
−/−
mice. Shotgun metagenomic-sequencing revealed a marked increase in the relative abundance of
L. johnsonii
in intestinal tissues of MyD88
−/−
mice compared to WT mice.
Lactobacillus johnsonii
was detected most frequently from multiple systemic tissues and at higher levels in MyD88
−/−
mice compared to WT mice. Viable
L. johnsonii
strains were recovered from different cell types sorted from intestinal and systemic tissues of WT and MyD88
−/−
mice.
L. johnsonii
could persist in dendritic cells and may represent murine immunomodulatory endosymbionts.
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