Intestinal Alkaline Phosphatase: A Review of This Enzyme Role in the Intestinal Barrier Function

Abstract

Intestinal alkaline phosphatase (IALP) has recently assumed a special relevance, being the subject of study in the prevention and treatment of certain diseases related to leaky gut. This brush border enzyme (ecto-enzyme) plays an important role in the maintenance of intestinal microbial homeostasis and intestinal barrier function through its ability to dephosphorylate lipopolysaccharide (LPS). This review addresses how IALP and intestinal barrier dysfunction may be implicated in the pathophysiology of specific diseases such as inflammatory bowel disease, necrotizing enterocolitis, and metabolic syndrome. The use of IALP as a possible biomarker to assess intestinal barrier function and strategies to modulate IALP activity are also discussed.

Keywords: inflammatory bowel disease; intestinal alkaline phosphatase; intestinal barrier function; low-grade chronic inflammation; metabolic dysfunction; necrotizing enterocolitis; obesity.

Figure 1

Detoxification of Gram-negative bacterial lipopolysaccharide (LPS) by intestinal alkaline phosphatase (IALP). 1—Absence of intestinal alkaline phosphatase: LPS binds to Toll-like receptor 4 (TLR4); 2—presence of IALP: lipid A phosphate group from LPS is dephosphorylated; 3—LPS dephosphorylation: no binding of LPS to TLR4 receptor, preventing the triggering of an inflammatory cascade. The red cross in the figure means no binding of LPS to TLR4.

Figure 2

(A) Diet has an impact on the modulation of IALP (intestinal alkaline phosphatase) activity. Foods rich in fermentable fiber (e.g., artichoke, asparagus) are used as a substrate for the microbiota. This fermentation results in the production of short-chain fatty acids (e.g., butyrate) that increase IALP activity. On the other hand, consumption of foods rich in chlorogenic acid (coffee, artichoke, apple, pear, tomato, and avocado) also increases the activity/expression of IALP. (B) The gut microbiota may modulate the expression/activity of IALP. On the one hand, butyrate-producing bacteria (Gram-positive bacteria) may increase IALP due to the increase in butyrate. On the other hand, Gram-negative bacteria may also increase IALP due to the presence of LPS (the presence of LPS as a substrate may enhance enzyme activity).

Figure 2

(A) Diet has an impact on the modulation of IALP (intestinal alkaline phosphatase) activity. Foods rich in fermentable fiber (e.g., artichoke, asparagus) are used as a substrate for the microbiota. This fermentation results in the production of short-chain fatty acids (e.g., butyrate) that increase IALP activity. On the other hand, consumption of foods rich in chlorogenic acid (coffee, artichoke, apple, pear, tomato, and avocado) also increases the activity/expression of IALP. (B) The gut microbiota may modulate the expression/activity of IALP. On the one hand, butyrate-producing bacteria (Gram-positive bacteria) may increase IALP due to the increase in butyrate. On the other hand, Gram-negative bacteria may also increase IALP due to the presence of LPS (the presence of LPS as a substrate may enhance enzyme activity).