Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition.
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.
Goldberg
Ross F
RF
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Austen
William G
WG
Zhang
Xiaobo
X
Munene
Gitonga
G
Mostafa
Golam
G
Biswas
Shaluk
S
McCormack
Michael
M
Eberlin
Kyle R
KR
Nguyen
John T
JT
Tatlidede
Hamit S
HS
Warren
H Shaw
HS
Narisawa
Sonoko
S
Millán
Jose L
JL
Hodin
Richard A
RA
D000469:Alkaline Phosphatase; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000502:physiology*; D018988:Bacterial Translocation; D002460:Cell Line; D003422:Critical Care; D016638:Critical Illness; D004750:Enteral Nutrition; D058851:GPI-Linked Proteins; D006801:Humans; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000276:immunology*; D007422:Intestines / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D008871:Microvilli / Q000201:enzymology; D013217:Starvation / Q000276:immunology
D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; C063088:ALPI protein, human; D000469:Alkaline Phosphatase