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Intestinal Alkaline Phosphatase


Inflammatory Bowel Diseases (IBD) such as Crohn's disease are thought to result from an interplay between genetics, and altered-microbiome, and a defective gut barrier.


These factors seem to be core drivers of the disease process. as they drive a state of dysbiosis (undergrowth or imbalance of supportive microbiota; while harmful microbiota overgrow).


Regulating and preventing dysbiosis seems to be holy grail in IBD management and also with other conditions like IBS and SIBO .


We will be talking all about this in my upcoming Beyond SIBO course


Recently, research is showing that Intestinal Alkaline Phosphatase (IAP) , a hydrolase enzyme that mainly expresses in the duodenum of the small intestine, may be a key part of the IBD process. IBD patients (likely specifically Crohn's patients) may be genetically predisposed to low IAP. (Singh,et.al,)


IAP plays several key roles in regulating the gut barrier such as:

  • Regulating bicarbonate secretion (involved in intestinal Ph,

  • Detoxifying lipopolysaccharide (LPS) which are the potential harmful cell wall debris of gram negative bacteria

  • Regulating gut microbes

  • Dephosphorylating proinflammatory peptides (nucleotides).

  • Exhibiting anti-inflammatory effects via Toll-like Receptor-4 (TLR-4) dependent manner.

In a sense one of its key roles is autophagy.; which is a self regulating mechanism in organisms that remove old cells and recycles waste products.


Source: (Estaki,et.al )


IAP levels found higher in Type 0, and Type B blood types and lowest in type A.


Nonetheless , having healthy levels of IAP may be seen as a key protector against Dysbiosis


Interestingly enough , In mouse models , the administration of exogenous IAP has been shown to reduce Small Intestinal Bacterial Overgrowth (Singh,et.al, 2020)


Are there foods, supplements, and dietary factors that may influence IAP levels?


The short answer is ": "likely and more information is to come".


Dietary factors to alter IAP have been inconsistent in the research likely so I can’t comfortably say how to modify it with diet at this point other than fiber in the diet will likely increase it. In rodent studies the consumption of Non-digestible Oligosaccharides (ie. GOS, FOS) elevated colonic levels of IAP in rats fed a high fat diet. (Okazaki,et.al)


Other dietary influences on IAP can be postulated and these approaches might be worth looking into especially in resistant to treatment Crohn's Disease





In the IBD patient these are generally good principles any ways


Maximize consumption of IAP activators

  • Oysters

  • Pumpkin

  • Sweet Potato

  • Carrots

  • Herring

  • Mackerel

  • Salmon

  • Sardines

  • Butter (likely due to its source of butyrate

  • Dietary Fiber (due to prebiotic supply and butyrate supply)

  • Healthy Omega-6 sources (sunflower seeds, walnuts, pumpkin seeds)


Minimize consumption of IAP inhibitors

  • Artificial sweeteners (a source of phenylalanine)

  • Hard and Processed cheese

  • Processed meats

  • Highly saturated fats

  • Phytates (which can be minimized by soaking grains and legumes overnight prior to consumption)

Note: currently in the literature it highlights the importance of Omega 3/Omega 6 balance in optimizing the effect of IAP (Estaki,et.al)


There likely will be day soon where IAP is given as an exogenous medicine in the meantime these dietary principles are guidepost to follow. They happen to align with a healthy Mediterranean style diet anyway.



References:




Estaki, M., DeCoffe, D., & Gibson, D. L. (2014). Interplay between intestinal alkaline phosphatase, diet, gut microbes and immunity.World Journal of Gastroenterology,20(42), 15650.https://doi.org/10.3748/wjg.v20.i42.15650



Okazaki, Y., & Katayama, T. (2019). Consumption of non-digestible oligosaccharides elevates colonic alkaline phosphatase activity by up-regulating the expression of IAP-I, with increased mucins and microbial fermentation in rats fed a high-fat diet. The British journal of nutrition, 121(2), 146–154. https://doi.org/10.1017/S0007114518003082



Singh, S. B., Carroll-Portillo, A., Coffman, C., Ritz, N. L., & Lin, H. C. (2020). Intestinal Alkaline Phosphatase Exerts Anti-Inflammatory Effects Against Lipopolysaccharide by Inducing Autophagy. Scientific reports, 10(1), 3107. https://doi.org/10.1038/s41598-020-59474-6



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