title: Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition.
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.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Ross F
authors.initials: RF
authors.lastname: Goldberg
authors.forename: William G
authors.initials: WG
authors.lastname: Austen
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhang
authors.forename: Gitonga
authors.initials: G
authors.lastname: Munene
authors.forename: Golam
authors.initials: G
authors.lastname: Mostafa
authors.forename: Shaluk
authors.initials: S
authors.lastname: Biswas
authors.forename: Michael
authors.initials: M
authors.lastname: McCormack
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Eberlin
authors.forename: John T
authors.initials: JT
authors.lastname: Nguyen
authors.forename: Hamit S
authors.initials: HS
authors.lastname: Tatlidede
authors.forename: H Shaw
authors.initials: HS
authors.lastname: Warren
authors.forename: Sonoko
authors.initials: S
authors.lastname: Narisawa
authors.forename: Jose L
authors.initials: JL
authors.lastname: Millán
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hodin
mesh_terms: 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
chemical_list: D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; C063088:ALPI protein, human; D000469:Alkaline Phosphatase