title: Prevention of antibiotic-associated metabolic syndrome in mice by intestinal alkaline phosphatase.
abstract: OBJECTIVE
  To examine whether co-administration of intestinal alkaline phosphatase (IAP) with antibiotics early in life may have a preventive role against metabolic syndrome (MetS) in mice.
  
  
  METHODS
  A total of 50 mice were allocated to four treatment groups after weaning. Mice were treated with azithromycin (AZT) ± IAP, or with no AZT ± IAP, for three intermittent 7-day cycles. After the last treatment course, the mice were administered a regular chow diet for 5 weeks and subsequently a high-fat diet for 5 weeks. Body weight, food intake, water intake, serum lipids, glucose levels and liver lipids were compared. 16S rRNA gene pyrosequencing was used to determine the differences in microbiome composition.
  
  
  RESULTS
  Exposure to AZT early in life rendered mice susceptible to MetS in adulthood. Co-administration of IAP with AZT completely prevented this susceptibility by decreasing total body weight, serum lipids, glucose levels and liver lipids to the levels of control mice. These effects of IAP probably occur as a result of changes in the composition of specific bacterial taxa at the genus and species levels (e.g. members of Anaeroplasma and Parabacteroides).
  
  
  CONCLUSIONS
  Co-administration of IAP with AZT early in life prevents mice from susceptibility to the later development of MetS. This effect is associated with alterations in the composition of the gut microbiota. IAP may represent a novel treatment against MetS in humans.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Economopoulos
authors.affiliation: Departments of Molecular Biology and Botany, University of Wyoming, Laramie, WY, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Ward
authors.affiliation: Research and Testing Laboratory, Lubbock, TX, USA.|Department of Biological Sciences, Texas Tech University, Lubbock, TX, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Phillips
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Teshager
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Patel
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Mohamed
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hakimian
authors.affiliation: Research and Testing Laboratory, Lubbock, TX, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Cox
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Moaven
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kaliannan
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Alam
authors.affiliation: Lipid Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Haller
authors.affiliation: Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Goldstein
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Bhan
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Malo
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Hodin
mesh_terms: D000127:Acholeplasma / Q000145:classification / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification; D000469:Alkaline Phosphatase / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D017963:Azithromycin / Q000009:adverse effects*; D001439:Bacteroides / Q000145:classification / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification; D002417:Cattle; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements / Q000009:adverse effects; D064806:Dysbiosis / Q000139:chemically induced / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D007413:Intestinal Mucosa / Q000201:enzymology*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000209:etiology / Q000382:microbiology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D058889:Molecular Typing; D009765:Obesity / Q000150:complications / Q000209:etiology / Q000382:microbiology / Q000517:prevention & control; D014886:Weaning; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin; D000469:Alkaline Phosphatase
keywords: azithromycin; intestinal alkaline phosphatase; metabolic syndrome; mice