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Intestinal Alkaline Phosphatase Prevents Antibiotic-Induced Susceptibility to Enteric Pathogens

Alam, Sayeda Nasrin MD*; Yammine, Halim MD*; Moaven, Omeed MD*; Ahmed, Rizwan MD*; Moss, Angela K. MD*; Biswas, Brishti BS*; Muhammad, Nur MD*; Biswas, Rakesh BS*; Raychowdhury, Atri*; Kaliannan, Kanakaraju MD*; Ghosh, Sathi MD*; Ray, Madhury MD*; Hamarneh, Sulaiman R. MD*; Barua, Soumik*; Malo, Nondita S.*; Bhan, Atul K. MD; Malo, Madhu S. MD, PhD*; Hodin, Richard A. MD*

Annals of Surgery:
doi: 10.1097/SLA.0b013e31828fae14
Original Articles
Abstract

Objective: To determine the efficacy of oral supplementation of the gut enzyme intestinal alkaline phosphatase (IAP) in preventing antibiotic-associated infections from Salmonella enterica serovar Typhimurium (S. Typhimurium) and Clostridium difficile.

Background: The intestinal microbiota plays a pivotal role in human health and well-being. Antibiotics inherently cause dysbiosis, an imbalance in the number and composition of intestinal commensal bacteria, which leads to susceptibility to opportunistic bacterial infections. Previously, we have shown that IAP preserves the normal homeostasis of intestinal microbiota and that oral supplementation with calf IAP (cIAP) rapidly restores the normal gut flora. We hypothesized that oral IAP supplementation would protect against antibiotic-associated bacterial infections.

Methods: C57BL/6 mice were treated with antibiotic(s) ± cIAP in the drinking water, followed by oral gavage of S. Typhimurium or C. difficile. Mice were observed for clinical conditions and mortality. After a defined period of time, mice were killed and investigated for hematological, inflammatory, and histological changes.

Results: We observed that oral supplementation with cIAP during antibiotic treatment protects mice from infections with S. Typhimurium as well as with C. difficile. Animals given IAP maintained their weight, had reduced clinical severity and gut inflammation, and showed improved survival.

Conclusions: Oral IAP supplementation protected mice from antibiotic-associated bacterial infections. We postulate that oral IAP supplementation could represent a novel therapy to protect against antibiotic-associated diarrhea (AAD), C. difficile-associated disease (CDAD), and other enteric infections in humans.

In Brief

Intestinal alkaline phosphatase (IAP) preserves the normal homeostasis of intestinal microbiota and prevents antibiotic-associated dysbiosis. Here, we demonstrate that oral supplementation with calf IAP during antibiotic treatment protects mice from infections with Salmonella Typhimurium and Clostridium difficile.

Author Information

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

Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Reprints: Madhu S. Malo, MD, PhD, Department of Surgery, Massachusetts General Hospital, Jackson 812, 55 Fruit Stt, Boston, MA 02114. E-mail: mmalo@partners.org.

Supported by the National Institute of Health grants R01DK050623 and R01DK047186 to RAH, the Gates Foundation Grand Challenge Exploration Grant OPP1008158 to MSM, and the National Institutes of Health grant 2P30 DK43351 to the Center for the Study of Inflammatory Bowel Disease, MGH.

Disclosure: The authors declare no conflicts of interest.

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© 2014 by Lippincott Williams & Wilkins.