Papers of the 134th ASA Annual Meeting

A Novel Approach to Maintain Gut Mucosal Integrity Using an Oral Enzyme Supplement

Hamarneh, Sulaiman R. MD^*; Mohamed, Mussa M. Rafat MD^*; Economopoulos, Konstantinos P. MD, PhD^*; Morrison, Sara A. MD^*; Phupitakphol, Tanit MD^*; Tantillo, Tyler J. BS^*; Gul, Sarah S. MD^*; Gharedaghi, Mohammad Hadi MD^*; Tao, Qingsong MD^*; Kaliannan, Kanakaraju MD^*; Narisawa, Sonoko PhD^†; Millán, José L. PhD^†; van der Wilden, Gwendolyn M. PhD, MSc^*; Fagenholz, Peter J. MD^*; Malo, Madhu S. MD, PhD^*; Hodin, Richard A. MD^*

Author Information

^*Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and

^†Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA.

Reprints: Richard A. Hodin, MD, Department of Surgery, Massachusetts General Hospital, 15 Parkman Street, Boston, MA 02114. E-mail: [email protected].

S.R.H. and M.M.R.M. contributed equally.

Disclosure: The authors declare no conflicting financial interests. Funding has been received from the National Institute of Health grants: NIH/NIDDK T32 DK007754 and NIH P30-DK040561 (R.A.H.).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.annalsofsurgery.com).

Annals of Surgery 260(4):p 706-715, October 2014. | DOI: 10.1097/SLA.0000000000000916

Objective:

To determine the role of intestinal alkaline phosphatase (IAP) in enteral starvation-induced gut barrier dysfunction and to study its therapeutic effect as a supplement to prevent gut-derived sepsis.

Background:

Critically ill patients are at increased risk for systemic sepsis and, in some cases, multiorgan failure leading to death. Years ago, the gut was identified as a major source for this systemic sepsis syndrome. Previously, we have shown that IAP detoxifies bacterial toxins, prevents endotoxemia, and preserves intestinal microbiotal homeostasis.

Methods:

WT and IAP-KO mice were used to examine gut barrier function and tight junction protein levels during 48-hour starvation and fed states. Human ileal fluid samples were collected from 20 patients postileostomy and IAP levels were compared between fasted and fed states. To study the effect of IAP supplementation on starvation-induced gut barrier dysfunction, WT mice were fasted for 48 hours +/− IAP supplementation in the drinking water.

Results:

The loss of IAP expression is associated with decreased expression of intestinal junctional proteins and impaired barrier function. For the first time, we demonstrate that IAP expression is also decreased in humans who are deprived of enteral feeding. Finally, our data demonstrate that IAP supplementation reverses the gut barrier dysfunction and tight junction protein losses due to a lack of enteral feeding.

Conclusions:

IAP is a major regulator of gut mucosal permeability and is able to ameliorate starvation-induced gut barrier dysfunction. Enteral IAP supplementation may represent a novel approach to maintain bowel integrity in critically ill patients.

Article Keywords

Keywords
enteral starvation, ICU patient, intestinal alkaline phosphatase, intestinal permeability, tight junctions, total parenteral nutrition

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