Vitamin A status modulates intestinal adaptation after partial small bowelresection

Background: Intestinal adaptation after loss of functional small bowel surf ace area is characterized by cellular hyperplasia and increased absorptive function. Interventions to enhance the adaptive response are needed to decr ease the morbidity and mortality associated with short bowel syndrome. Reti noic acid was shown to stimulate crypt cell proliferation in the adapting r emnant rat ileum by 6 hours after resection. Thus, vitamin A, which is requ ired for normal epithelial cell proliferation and differentiation and which can modulate programmed cell death, may play an important role in the adap ting intestine. On the basis of these observations, the effects of vitamin A deficiency on intestinal morphology, Epithelial cell proliferation, and a poptosis in the adapting intestine after resection were investigated. Metho ds: Weanling male Sprague-Dawley rats fed either a vitamin A-deficient or - sufficient diet for 58 days underwent 70% proximal small bowel resection. T he deficient rats were divided into cohorts that were either maintained on the experimental diet after surgery or replenished with vitamin A 20 hours before surgery and switched to the control diet after surgery. Results: Ten days after resection, vitamin A-deficient rats exhibited a markedly blunte d adaptive response. The adaptive increase in villus height and crypt depth was absent in the deficient rats. However, adaptive increases in crypt cel l proliferation were not attenuated by vitamin A deficiency, and there were no differences in apoptotic indices. Conclusions: Vitamin A deficiency inh ibits the adaptive response to partial small bowel resection, supporting a role for vitamin A in the adaptive process. Changes in cellular proliferati on or programmed cell death are not sufficient to account for this inhibiti on. This model system will be useful for examining the role of other mechan isms, such as changes in cell-cell and cell-extracellular matrix interactio ns, and rates of epithelial cell migration and cell extrusion.