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.

Recent advances with alkaline phosphatase isoenzymes and their inhibitors

“…This leads to a significant increase in the growth of aerobic and anaerobic bacteria in the intestine (Figure 2). [ 35 ]…”

The role of gut microbiome and associated metabolome in the regulation of neuroinflammation in multiple sclerosis and its implications in attenuating chronic inflammation in other inflammatory and autoimmune disorders

“…These long hydrocarbon chains are directly involved in the regulation of metabolic endotoxaemia, a disorder in which an overabundance of lipopolysaccharide (LPS) ‐producing gut bacteria leads to activation of Toll‐like receptor 4 (TLR4), producing widespread chronic low‐grade inflammation . Omega‐3 fatty acids display an anti‐inflammatory phenotype when ingested in higher proportions than omega‐6 fatty acids due to the activation of intestinal alkaline phosphatase, an antimicrobial peptide that targets Gram‐negative organisms while simultaneously promoting the growth of Gram‐positive organisms . In addition to reducing Gram‐negative abundance, intestinal alkaline phosphatase exhibits anti‐toxic effects by hydrolysing phosphate groups coupled to Lipid‐A present on degraded LPS, reducing its binding efficiency to the TLR4 100‐fold .…”

“…Omega‐3 fatty acids display an anti‐inflammatory phenotype when ingested in higher proportions than omega‐6 fatty acids due to the activation of intestinal alkaline phosphatase, an antimicrobial peptide that targets Gram‐negative organisms while simultaneously promoting the growth of Gram‐positive organisms . In addition to reducing Gram‐negative abundance, intestinal alkaline phosphatase exhibits anti‐toxic effects by hydrolysing phosphate groups coupled to Lipid‐A present on degraded LPS, reducing its binding efficiency to the TLR4 100‐fold . TLR4 activation leads to cryopyrin inflammasome activation releasing subsequent amounts of pro‐inflammatory cytokines, TNF‐ α , IL‐1 and IL‐6 circulating in host organisms .…”

Effects of intestinal alkaline phosphatase on intestinal barrier function in a cecal ligation and puncture (CLP)‐induced mouse model for sepsis

“…2 The gastrointestinal tract has been hypothesized to play an im- Recent data suggest a role for intestinal alkaline phosphatase (IAP), a brush border-bound alkaline phosphatase subtype solely expressed by enterocytes, in sepsis. 4 Although IAP is ubiquitously expressed in the gastrointestinal tract, its distribution is variable with the highest expression levels in the duodenum and IAP expression levels decreasing over the length of the intestine. Among many other functions, IAP has been documented to be involved in the regulation of duodenal bicarbonate secretion 5,6 and in lipid absorption by the intestinal epithelium.…”