Hyaluronan 35Â kDa treatment protects mice from Citrobacter rodentium infection and induces epithelial tight junction protein ZO-1 in vivo

- Hyaluronan 35kDa (HA35) treatment inhibits murine Citrobacter rodentium infection, a model of human enteropathogenic E. coli.
- Biosynthetic HA fragments induce ZO-1 expression in the intestinal epithelium of the distal colon in healthy mice.
- Oral HA35 treatment enhances epithelial ZO-1 expression in murine infection and colitis models.
- Treatment with HA35 reduces the intestinal permeability in mouse intestine damaged with dextran sulfate sodium (DSS).
- Treatment with HA35 promotes intestinal barrier function in vivo.

Maintaining a healthy intestinal barrier, the primary physical barrier between intestinal microbiota and the underlying lamina propria, is critical for optimal health. Epithelial integrity is essential for the prevention of the entrance of luminal contents, such as bacteria and their products, through the large intestinal barrier. In this study, we investigated the protective functions of biosynthetic, specific sized, hyaluronan around 35 kDa (HA35) on intestinal epithelium in healthy mice, as well as mice infected Citrobacter rodentium, an established model that mimics infection with a serious human pathogen, enteropathogenic E. coli (EPEC). Our results reveal that treatment with HA35 protects mice from Citrobacter infection and enhances the epithelial barrier function. In particular, we have found that HA35 induces the expression of tight junction protein zonula occludens (ZO)-1 in both healthy and Citrobacter infected mice, as demonstrated by immunoflurorescence and Western blot analyses. Furthermore, we determined that HA35 treatment enhances ZO-1 expression and reduces intestinal permeability at the early stages of dextran sulfate sodium (DSS)-induced colitis in mice. Together, our data demonstrate that the expression and functionality of tight junctions, are increased by HA35 treatment, suggesting a novel mechanism for the protection from Citrobacter infection.