Vitamin A deficiency creates persistent shedding of Citrobacter rodentium and potential reservoirs for the spread of enteric pathogens (MUC5P.755)

Vitamin A deficiency remains a public health concern in developing countries and is associated with increased susceptibility to infectious disease and childhood mortality. We utilized Citrobacter rodentium to model human enteric infections. 40% of vitamin A deficient (A-) mice developed a severe and lethal infection. All of the vitamin A sufficient (A+) mice survived and cleared the infection by day 25. Retinoic acid (RA, active form of vitamin A) treatment of A- mice before and at the time of infection resulted in clearance of C. rodentium with the same kinetics as the A+ mice. Additionally, RA treatment of A- mice at the peak of the infection eliminated C. rodentium within 16 days of treatment. Although the A- mice remained infected at day 37, colon inflammation had resolved to that found in A+ mice. All of the A- and A+ mice were able to clear systemic challenge with C. rodentium indicating that A- mice are able to control systemic bacterial infection. Furthermore, the increased mortality of A- mice during infection was not due to systemic cytokine production or increased C. rodentium pathogenicity. Instead the A- mice seem to have developed a severe gut infection but 60% of the A- mice were able to survive and resolve the inflammation. Our work suggests that improvements in vitamin A status and/or RA treatments may decrease susceptibility to enteric pathogens and eliminate potential carriers from spreading infection to susceptible populations.