title: Bloom and bust: intestinal microbiota dynamics in response to hospital exposures and Clostridium difficile colonization or infection.
abstract: BACKGROUND
  Clostridium difficile infection (CDI) is the leading infectious cause of nosocomial diarrhea. Hospitalized patients are at increased risk of developing CDI because they are exposed to C. difficile spores through contact with the hospital environment and often receive antibiotics and other medications that can disrupt the integrity of the indigenous intestinal microbiota and impair colonization resistance. Using whole metagenome shotgun sequencing, we examined the diversity and composition of the fecal microbiota in a prospective cohort study of 98 hospitalized patients.
  
  
  RESULTS
  Four patients had asymptomatic C. difficile colonization, and four patients developed CDI. We observed dramatic shifts in the structure of the gut microbiota during hospitalization. In contrast to CDI cases, asymptomatic patients exhibited elevated relative abundance of potentially protective bacterial taxa in their gut at the onset of C. difficile colonization. Use of laxatives was associated with significant reductions in the relative abundance of Clostridium and Eubacterium; species within these genera have previously been shown to enhance resistance to CDI via the production of secondary bile acids. Cephalosporin and fluoroquinolone exposure decreased the frequency of Clostridiales Family XI Incertae Sedis, a bacterial family that has been previously associated with decreased CDI risk.
  
  
  CONCLUSIONS
  This study underscores the detrimental impact of antibiotics as well as other medications, particularly laxatives, on the intestinal microbiota and suggests that co-colonization with key bacterial taxa may prevent C. difficile overgrowth or the transition from asymptomatic C. difficile colonization to CDI.
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.|Génome Québec Innovation Centre, McGill University, Montréal, Québec, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Vincent
authors.affiliation: Jewish General Hospital, Montréal, Québec, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Miller
authors.affiliation: Devil's Staircase Consulting, North Vancouver, British Columbia, Canada.
authors.forename: Thaddeus J
authors.initials: TJ
authors.lastname: Edens
authors.affiliation: New York Genome Center, New York, NY, USA.
authors.forename: Sudeep
authors.initials: S
authors.lastname: Mehrotra
authors.affiliation: Génome Québec Innovation Centre, McGill University, Montréal, Québec, Canada.|Department of Human Genetics, McGill University, Montréal, Québec, Canada.
authors.forename: Ken
authors.initials: K
authors.lastname: Dewar
authors.affiliation: School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada. amee.manges@ubc.ca.
authors.forename: Amee R
authors.initials: AR
authors.lastname: Manges
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001647:Bile Acids and Salts / Q000096:biosynthesis; D002511:Cephalosporins / Q000009:adverse effects; D016360:Clostridioides difficile / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D003428:Cross Infection / Q000382:microbiology* / Q000473:pathology; D003967:Diarrhea / Q000209:etiology / Q000382:microbiology* / Q000473:pathology; D004761:Enterocolitis, Pseudomembranous / Q000209:etiology / Q000382:microbiology* / Q000473:pathology; D005051:Eubacterium / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D006801:Humans; D054368:Laxatives / Q000009:adverse effects; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D002511:Cephalosporins; D024841:Fluoroquinolones; D054368:Laxatives
keywords: Antimicrobials; Clostridium difficile infection; Intestinal microbiota; Medications; Whole metagenome shotgun sequencing