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Intestinal Alkaline Phosphatase (IAP)

Intestinal Alkaline Phosphatase (IAP) is an enzyme secreted by the intestinal epithelial cells. It is at the crossroads between diet, lipid absorption, intestinal microbiome, LPS, and inflammation, causative agents in aging, obesity, and other metabolic diseases. Intestinal alkaline phosphatase is vital for intestinal health. IAP's role in the intestine encompasses protection from systemic infections and chronic inflammatory diseases such as inflammatory bowel disease.

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Intestinal alkaline phosphatase is a member of the alkaline phosphatase family and is one of the four types known to exist in humans: tissue non-specific alkaline phosphatase (TNAP), placental alkaline phosphatase (PLAP), germ cell alkaline phosphatase (GCALP), and intestinal alkaline phosphatase (IAP). IAP is produced by small intestine enterocytes and secreted into the lumen, blood, and stool. IAP deficiency has been linked to a plethora of conditions, such as IBD, type 2 diabetes, ischemic heart disease, aging, necrotizing enterocolitis, obesity, and metabolic syndrome, among others.

Many functions thus far have been ascribed to intestinal alkaline phosphatase:

  1. IAP detoxifies lipopolysaccharide (LPS), which is responsible for causing gut permeability and inflammation
  2. IAP dephosphorylates pro-inflammatory nucleotides such as ATP and UDP
  3. IAP regulates bicarbonate secretion and maintains duodenal pH
  4. IAP protects the intestinal epithelial barrier by regulating the level of tight junction proteins such as occludins, claudins, and zonulin
  5. IAP regulates gut microbial communities
  6. IAP appears to positively regulate antimicrobial proteins, such as lysozymes that control the bacterial numbers in the intestine
  7. IAP induces autophagy, a vital innate immune pathway known for its role in barrier function, inflammation, and antimicrobial functions
  8. Some reports also suggest a positive correlation between IAP and mucins that make up the mucus layer in the intestine.

Supplementation with intestinal alkaline phosphatase has been tested in clinical and pre-clinical studies for its protective role in various diseases.

Common inducers such as butyrate, vitamin D, and zinc can upregulate intestinal alkaline phosphatase, all of which have been demonstrated to play essential roles in maintaining intestinal homeostasis.

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