INTRODUCTION: Chronic feeding with immune-enhancing enteral diets (IED) provides benefits based on composition of the IED, route of IED delivery and timing of IED delivery. Acute feeding in naive rats promotes gut blood flow and pro-inflammatory cytokines in the ileum. We hypothesized that chronic IED would shift gut immune status to a pro-inflammatory state during chronic sepsis. METHODS: Five days prior to initiating feeding with IED or control diet (CD), gauze was implanted subcutaneously in the backs of male Sprague-Dawley rats. Rats were randomly assigned to be fed for 5 days either IED (Impact, Novartis) or CD (Boost, Mead-Johnson) and randomly assigned to receive back-sponge injections of either normal saline (NS, 2 mL) or Escherichia coli + Bacteroides fragilis (EC, 10⁹ CFU of each in 2 mL NS). After 3 days, rats were anesthetized and gut tissue samples were harvested and frozen at -80C. Tissue protein was extracted and ELISA was performed for interleukin-10 (IL-10) and interferon-gamma (IFN-g). RESULTS: (See graph) In rats fed CD, chronic sepsis did not alter IL-10 or IFN-g gut tissue levels. However, in IED-fed rats, EC significantly decreased IL-10 and increased IFN-g protein levels in the gut. CONCLUSIONS: In contrast to feeding with the control diet, chronic IED feeding in septic rats produced a pro-inflammatory state via decreased IL-10 and elevated IFN-g. Both elevating IFN-g and decreasing IL-10 promote gut IgA expression and enhance gut inflammatory processes. These data suggest that IED promotes gut immunity by altering tissue cytokine production in addition to promoting intestinal blood flow.