Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the concentration of luminal nucleotide triphosphates.

Published

Journal Article

The intestinal microbiota plays a pivotal role in maintaining human health and well-being. Previously, we have shown that mice deficient in the brush-border enzyme intestinal alkaline phosphatase (IAP) suffer from dysbiosis and that oral IAP supplementation normalizes the gut flora. Here we aimed to decipher the molecular mechanism by which IAP promotes bacterial growth. We used an isolated mouse intestinal loop model to directly examine the effect of exogenous IAP on the growth of specific intestinal bacterial species. We studied the effects of various IAP targets on the growth of stool aerobic and anaerobic bacteria as well as on a few specific gut organisms. We determined the effects of ATP and other nucleotides on bacterial growth. Furthermore, we examined the effects of IAP on reversing the inhibitory effects of nucleotides on bacterial growth. We have confirmed that local IAP bioactivity creates a luminal environment that promotes the growth of a wide range of commensal organisms. IAP promotes the growth of stool aerobic and anaerobic bacteria and appears to exert its growth promoting effects by inactivating (dephosphorylating) luminal ATP and other luminal nucleotide triphosphates. We observed that compared with wild-type mice, IAP-knockout mice have more ATP in their luminal contents, and exogenous IAP can reverse the ATP-mediated inhibition of bacterial growth in the isolated intestinal loop. In conclusion, IAP appears to promote the growth of intestinal commensal bacteria by inhibiting the concentration of luminal nucleotide triphosphates.

Full Text

Duke Authors

Cited Authors

  • Malo, MS; Moaven, O; Muhammad, N; Biswas, B; Alam, SN; Economopoulos, KP; Gul, SS; Hamarneh, SR; Malo, NS; Teshager, A; Mohamed, MMR; Tao, Q; Narisawa, S; Millán, JL; Hohmann, EL; Warren, HS; Robson, SC; Hodin, RA

Published Date

  • May 2014

Published In

Volume / Issue

  • 306 / 10

Start / End Page

  • G826 - G838

PubMed ID

  • 24722905

Pubmed Central ID

  • 24722905

Electronic International Standard Serial Number (EISSN)

  • 1522-1547

International Standard Serial Number (ISSN)

  • 0193-1857

Digital Object Identifier (DOI)

  • 10.1152/ajpgi.00357.2013

Language

  • eng