Dietary glutamine and oral antibiotics each improve indexes of gut barrier function in rat short bowel syndrome.

Short bowel syndrome (SBS) is associated with gut barrier dysfunction. We examined effects of dietary glutamine (GLN) or oral antibiotics (ABX) on indexes of gut barrier function in a rat model of SBS. Adult rats underwent a 60% distal small bowel + proximal colonic resection (RX) or bowel transection (TX; control). Rats were pair fed diets with or without l-GLN for 20 days after operation. Oral ABX (neomycin, metronidazole, and polymyxin B) were given in some RX rats fed control diet. Stool secretory immunoglobulin A (sIgA) was measured serially. On day 21, mesenteric lymph nodes (MLN) were cultured for gram-negative bacteria. IgA-positive plasma cells in jejunum, stool levels of flagellin- and lipopolysaccharide (LPS)-specific sIgA, and serum total, anti-flagellin- and anti-LPS IgG levels were determined. RX caused gram-negative bacterial translocation to MLN, increased serum total and anti-LPS IgG and increased stool total sIgA. After RX, dietary GLN tended to blunt bacterial translocation to MLN (-29%, P = NS) and significantly decreased anti-LPS IgG levels in serum, increased both stool and jejunal mucosal sIgA and increased stool anti-LPS-specific IgA. Oral ABX eliminated RX-induced bacterial translocation, significantly decreased total and anti-LPS IgG levels in serum, significantly decreased stool total IgA and increased stool LPS-specific IgA. Partial small bowel-colonic resection in rats is associated with gram-negative bacterial translocation from the gut and a concomitant adaptive immune response to LPS. These indexes of gut barrier dysfunction are ameliorated or blunted by administration of dietary GLN or oral ABX, respectively. Dietary GLN upregulates small bowel sIgA in this model.

Trophic effects of interleukin-11 in rats with experimental short bowel syndrome.

Interleukin-11 (IL-11) is a multifunctional cytokine, derived from bone marrow stromal cells, that stimulates proliferation of stem/progenitor precursor cells in the small intestinal crypts and accelerates recovery of intestinal mucosa after cytoablative therapy. This study evaluates whether IL-11 can improve the function and structure of the small intestine and enhance adaptation in an experimental model of short bowel syndrome. After 90% small bowel resection, 32 Sprague-Dawley rats were divided randomly into eight experimental groups of four animals each. Four groups were treated with IL-11 (125 micrograms/kg twice daily, subcutaneously), and the four control groups were treated with a similar volume (0.1%) of bovine serum albumin (BSA). The animals were weighed daily and were killed on day 2, 4, 6, or 8; remnant small bowel was evaluated for villus height and crypt cell mitosis. The body weight of the animals that received IL-11 was significantly greater at the beginning of postoperative day 4 in comparison to that of the BSA groups (P < .01 during days 5 to 7). The rats that had IL-11 also had significantly greater villus height and crypt cell mitotic rates (P < .05). These observations suggest that IL-11 has a trophic effect on the small bowel during the adaptive phase that follows massive bowel resection and may be useful in the treatment of short bowel syndrome.

Effects of selenium supplementation on immune parameters in gut failure patients on home parenteral nutrition.

The relationships between some parameters of the immune response and selenium were investigated in five patients receiving home parenteral nutrition for short-bowel syndrome. They were first submitted to a relative depletion by providing 20 micrograms selenium/day as L-selenomethionine for 1 mo. Then, daily selenium intake was raised to 200 micrograms for 2-4 mo. On entering the study, the patients presented a relatively good health status, and immunological parameters were at the lowest limit of the normal range. Four patients rapidly responded to the 200-micrograms supplementation by a continuous increase in their plasma selenium levels, whereas the fifth patient showed a moderate and late increase. At the end of the trial, there was an improvement in the lymphocyte response to pokeweed and phytohemagglutinin mitogens in four patients and to CD3 in three patients. The response to two of three antigens (Candidin, Varidase) tested was also enhanced in the same patients, but the response to the third antigen (tetanus toxoid) was uniformly low in all patients. The only patient showing essentially no immune improvement after selenium supplementation was the one with a low and delayed increase in plasma selenium. This study supports a role for selenium in the maintenance of an optimal immune response in humans.