S1291 Zinc Promotes Intestinal Barrier Integrity and Health During Colitis

Introduction: An estimated 17% of the global population is at risk of inadequate zinc (Zn) intake. Even slight Zn deprivation leads to significantly impaired physiological functions. The gastrointestinal tract is particularly vulnerable to depletion as maintenance of intestinal homeostasis and the resident microbiota require Zn. Zn deficiency mediating loss of intestinal homeostasis and microbial dysbiosis have recently been proposed as mechanistic pathways for the development and severity of inflammatory bowel disease (IBD). However, the relationship between Zn, the gastrointestinal microbiota and IBD pathogenesis remains unclear. Methods: Utilizing both in vivo and in vitro models, we investigated the relationship between zinc deficiency, pathobiont infection, and IBD severity. We utilized Dextran sodium sulfate (DSS) to induce colitis. Mice consumed 2.5% DSS in their drinking water for 10 days before sacrifice. On days 2-10, they were gavaged daily with 200 mg/dose of Zinpro. Select groups were gavaged Adherent-invasive E. coli (1x108 CFU) on days 4, 5, and 6. We assessed the effects of Zn supplementation using 3 primary outcomes; 1) increases/decreases in Disease Activity Index (DAI), 2) gross pathology changes, and 3) histological evaluation. Using an in vitro approach we assessed epithelial barrier function. Intestinal cell cultures were treated with microbial products isolated from mice treated with DSS versus mice given water. Barrier function was measured via transepithelial electrical resistance. Results: Mice treated with Zinpro had significantly lower DAI, higher survival, and decreased weight loss as compared to the control. A small group of mice infected with AIEC, simulating a pathobiont bloom, who also received Zinpro recovered more quickly than those treated with phosphate buffer solution. AIEC also exacerbated DSS-colitis, likely due to increased intestinal burden of AIEC. Most strikingly, we demonstrated that Zinpro decreases membrane permeability following treatment with DSS-associated microbial products and significantly decreases the levels of intracellular AIEC. Treatment with Zinpro promoted mucosal wall integrity, decreased DAI, decreased infection rates, and improved histology. Conclusion: Together, this data suggests that Zinpro treatment significantly decreased colitis severity. Zinc supplementation early during colitis with subsequent pathobiont infection helped maintain intestinal wall membrane integrity (see Figure 1).Figure 1.: Moving in clockwise fashion Top Left – graph demonstrating the day(s) of administration of DSS, Zinpro, and AIEC. Top Right – Percent survival Bottom Right – Percent weight loss Bottom Left – Disease Activity Index.