title: Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota.
abstract: OBJECTIVE
  Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota.
  
  
  METHODS
  Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS) in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP) were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted.
  
  
  RESULTS
  ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels.
  
  
  CONCLUSIONS
  The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers.
authors.affiliation: Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.|Department of Animal Science, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Peris Mumbi
authors.initials: PM
authors.lastname: Munyaka
authors.affiliation: Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Eissa
authors.affiliation: Department of Internal Medicine, Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada.|Inflammatory Bowel Disease Clinical & Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Charles Noah
authors.initials: CN
authors.lastname: Bernstein
authors.affiliation: Department of Animal Science, University of Manitoba, Winnipeg, Manitoba, Canada.|Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Khafipour
authors.affiliation: Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.|Department of Internal Medicine, Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada.|Inflammatory Bowel Disease Clinical & Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Jean-Eric
authors.initials: JE
authors.lastname: Ghia
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002097:C-Reactive Protein / Q000276:immunology / Q000378:metabolism; D002437:Cefazolin / Q000009:adverse effects*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016264:Dextran Sulfate; D004198:Disease Susceptibility; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects* / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D007422:Intestines / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059013:Microbial Consortia / Q000187:drug effects* / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; C577686:interleukin-6, mouse; D002097:C-Reactive Protein; D016264:Dextran Sulfate; D002437:Cefazolin