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

Background: Numerous animal studies have demonstrated intestinal villu s atrophy occurs when luminal nutrition is withheld and total parenter al nutrition (TPN) is provided. Intestinal morphologic and functional changes have not been well studied in humans during TPN. Methods: Eigh t normal volunteers were hospitalized in the Clinical Research Center for 3 weeks. The subjects received TPN as an exclusive means of nutrit ional support for 14 days followed by 5 days of enteral refeeding with either a standard or a glutamine and arginine-supplemented formula En doscopic jejunal biopsies were taken before and after TPN and after en teral refeeding. Intestinal morphology was examined by Light and trans mission electron microscopy. Mucosa DNA, RNA, and protein concentratio ns 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. Resul ts: 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 incre ased 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-mannit ol 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)], in dicating increased intestinal permeability. The urinary Iactulose-mann itol ratio was significantly greater after refeeding with standard for mula than the free amino acid peptide formula with glutamine and argin ine (0.20 +/- 0.05, us 0.08 +/- 0.01, P =.05). No significant differen ces were noted in mucosal RNA, DNA, protein, DNA-protein or RNA-DNA ra tios or breath hydrogen after lactose ingestion after either TPN or en teral refeeding. No significant difference in plasma glutamine was fou nd during TPN (462.7 +/- 38.7 vs 491.8 +/- 46.1 mu mol/L) or after ent eral refeeding (457.3 +/- 51.4 mu mol/ L). Conclusions: Intestinal mor phologic and functional changes occur in humans for whom TPN is the so le nutritional source, although the findings in humans are substantial ly less significant than observed in animal models. The loss of mucosa l structure may be sufficient to cause increased intestinal permeabili ty, the clinical significance of which remains to be defined. Enteral nutrition is important in restoring and probably preventing morphologi c 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 g ut adaptation rather than degradation.