title: Intestinal alkaline phosphatase prevents antibiotic-induced susceptibility to enteric pathogens.
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.
authors.affiliation: *Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA †Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Sayeda Nasrin
authors.initials: SN
authors.lastname: Alam
authors.forename: Halim
authors.initials: H
authors.lastname: Yammine
authors.forename: Omeed
authors.initials: O
authors.lastname: Moaven
authors.forename: Rizwan
authors.initials: R
authors.lastname: Ahmed
authors.forename: Angela K
authors.initials: AK
authors.lastname: Moss
authors.forename: Brishti
authors.initials: B
authors.lastname: Biswas
authors.forename: Nur
authors.initials: N
authors.lastname: Muhammad
authors.forename: Rakesh
authors.initials: R
authors.lastname: Biswas
authors.forename: Atri
authors.initials: A
authors.lastname: Raychowdhury
authors.forename: Kanakaraju
authors.initials: K
authors.lastname: Kaliannan
authors.forename: Sathi
authors.initials: S
authors.lastname: Ghosh
authors.forename: Madhury
authors.initials: M
authors.lastname: Ray
authors.forename: Sulaiman R
authors.initials: SR
authors.lastname: Hamarneh
authors.forename: Soumik
authors.initials: S
authors.lastname: Barua
authors.forename: Nondita S
authors.initials: NS
authors.lastname: Malo
authors.forename: Atul K
authors.initials: AK
authors.lastname: Bhan
authors.forename: Madhu S
authors.initials: MS
authors.lastname: Malo
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hodin
mesh_terms: D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000209:etiology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D003967:Diarrhea / Q000209:etiology / Q000517:prevention & control; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D012480:Salmonella Infections / Q000209:etiology / Q000517:prevention & control*; D012486:Salmonella typhimurium; D013307:Streptomycin / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D005765:Gastrointestinal Agents; D000469:Alkaline Phosphatase; D013307:Streptomycin