Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition

Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3551-6. doi: 10.1073/pnas.0712140105. Epub 2008 Feb 21.

Abstract

Under conditions of starvation and disease, the gut barrier becomes impaired, and trophic feeding to prevent gut mucosal atrophy has become a standard treatment of critically ill patients. However, the mechanisms responsible for the beneficial effects of enteral nutrition have remained a mystery. Using in vitro and in vivo models, we demonstrate that the brush-border enzyme, intestinal alkaline phosphatase (IAP), has the ability to detoxify lipopolysaccharide and prevent bacterial invasion across the gut mucosal barrier. IAP expression and function are lost with starvation and maintained by enteral feeding. It is likely that the IAP silencing that occurs during starvation is a key component of the gut mucosal barrier dysfunction seen in critically ill patients.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alkaline Phosphatase
  • Animals
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / physiology*
  • Bacterial Translocation
  • Cell Line
  • Critical Care
  • Critical Illness
  • Enteral Nutrition*
  • GPI-Linked Proteins
  • Humans
  • Immunity, Innate
  • Intestinal Mucosa / immunology*
  • Intestines / enzymology
  • Mice
  • Mice, Knockout
  • Microvilli / enzymology
  • Starvation / immunology

Substances

  • Antigens, Neoplasm
  • GPI-Linked Proteins
  • ALPI protein, human
  • Alkaline Phosphatase