• Sayeda Nasrin Alam, Halim Yammine, Omeed Moaven, Rizwan Ahmed, Angela K Moss, Brishti Biswas, Nur Muhammad, Rakesh Biswas, Atri Raychowdhury, Kanakaraju Kaliannan, Sathi Ghosh, Madhury Ray, Sulaiman R Hamarneh, Soumik Barua, Nondita S Malo, Atul K Bhan, Madhu S Malo, and Richard A Hodin.
• *Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA †Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
• Ann. Surg. 2014 Apr 1; 259 (4): 715-22.

ObjectiveTo 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.BackgroundThe 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.MethodsC57BL/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.ResultsWe 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.ConclusionsOral 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.

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