PARENTERAL-NUTRITION IS ASSOCIATED WITH INTESTINAL MORPHOLOGIC AND FUNCTIONAL-CHANGES IN HUMANS

Background: Numerous animal studies have demonstrated intestinal villus atrophy occurs when luminal nutrition is withheld and total parenteral nutrition (TPN) is provided. Intestinal morphologic and functional changes have not been well studied in humans during TPN. Methods: Eight normal volunteers were hospitalized in the Clinical Research Center for 3 weeks. The subjects received TPN as an exclusive means of nutritional support for 14 days followed by 5 days of enteral refeeding with either a standard or a glutamine and arginine-supplemented formula Endoscopic jejunal biopsies were taken before and after TPN and after enteral refeeding. Intestinal morphology was examined by Light and transmission electron microscopy. Mucosa DNA, RNA, and protein concentrations were measured. Lactose breath hydrogen and intestinal permeability testing (urinary lactulose and mannitol excretion after an oral dose) were performed before and after TPN and after enteral refeeding. Results: Total mucosal thickness decreased after TPN (645 +/- 19 to 512 +/- 19 mu m, p = .003) and increased significantly towards baseline after enteral refeeding (575 +/- 19 mu m, P = .04). The change was related solely to villus height; crypt depth was unaffected. Villus cell count decreased from 179 +/- 15 to 163 +/- 12 after TPN (P = .03) and increased after enteral refeeding to 176 +/- 21 (P = .06). Crypt cell count was unaffected by TPN or refeeding. A nonsignificant decrease in the mitotic index after TPN was seen. Intracellular edema developed during TPN and resolved with enteral refeeding. The urinary lactulose-mannitol ratio increased with TPN [0.06 +/- 0.03 to 0.11 +/- 0.05 after TPN and to 0.14 +/- 0.09 after short-term enteral refeeding (P = .05)], indicating increased intestinal permeability. The urinary Iactulose-mannitol ratio was significantly greater after refeeding with standard formula than the free amino acid peptide formula with glutamine and arginine (0.20 +/- 0.05, us 0.08 +/- 0.01, P =.05). No significant differences were noted in mucosal RNA, DNA, protein, DNA-protein or RNA-DNA ratios or breath hydrogen after lactose ingestion after either TPN or enteral refeeding. No significant difference in plasma glutamine was found during TPN (462.7 +/- 38.7 vs 491.8 +/- 46.1 mu mol/L) or after enteral refeeding (457.3 +/- 51.4 mu mol/ L). Conclusions: Intestinal morphologic and functional changes occur in humans for whom TPN is the sole nutritional source, although the findings in humans are substantially less significant than observed in animal models. The loss of mucosal structure may be sufficient to cause increased intestinal permeability, the clinical significance of which remains to be defined. Enteral nutrition is important in restoring and probably preventing morphologic intestinal changes associated with TPN, and a peptide and free amino acid-based formula supplemented with glutamine and arginine may have some added role. Our findings also suggest sepsis is associated with gut adaptation rather than degradation.