Intestinal alkaline phosphatase: a summary of its role in clinical disease

Abstract

Over the past few years, there is increasing evidence implicating a novel role for Intestinal Alkaline Phosphatase (IAP) in mitigating inflammatory mediated disorders. IAP is an endogenous protein expressed by the intestinal epithelium that is believed to play a vital role in maintaining gut homeostasis. Loss of IAP expression or function is associated with increased intestinal inflammation, dysbiosis, bacterial translocation and subsequently systemic inflammation. As these events are a cornerstone of the pathophysiology of many diseases relevant to surgeons, we sought to review recent research in both animal and humans on IAP's physiologic function, mechanisms of action and current research in specific surgical diseases.

Keywords: Bacterial translocation; IAP; IBD; Intestinal microbiome; Metabolic syndrome; NEC; Sepsis.

Figure 1

Adapted from Lalles. [5] Summary of the multiple functions of intestinal alkaline phosphatase.

Figure 2

Diagram depicting the mechanisms by which IAP prevents LPS mediated inflammation. IAP dephosphorylates LPS resulting in a decrease in toxicity. Additionally, IAP blocks activation of NF-kB preventing translocation to the nucleus and expression of pro-inflammatory cytokines.

Figure 3

Adapted from Malo et al. [22] IAP helps to regulate the intestinal microbiome through dephosphorylation of phosphorylated nucleotides (ATP) in the intestinal lumen. Increasing quantities of ATP promote less bacterial diversity and inhibited the growth of commensal bacteria. This effect is ameliorated by dephoshorylation of nucleotides.

Figure 3

The premature intestine is associated with increased TLR4 expression. Shortly before the onset of necrotizing enterocolitis, there is an alteration in the microbiome with increased numbers of pathogenic bacteria. This leads to an increase LPS leading to mucosal injury and decreased mucosal restitution. However, as shown in figure A IAP deactivates intraluminal LPS preventing activation of the TLR4 cascade. Additionally, it is hypothesized that IAP prevents the alteration in the microbiome.