title: Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles.
abstract: The healthy microbiome protects against the development of Clostridium difficile infection (CDI), which typically develops following antibiotics. The microbiome metabolises primary to secondary bile acids, a process if disrupted by antibiotics, may be critical for the initiation of CDI.
  
  
  
  To assess the levels of primary and secondary bile acids associated with CDI and associated microbial changes.
  
  
  
  Stool and serum were collected from patients with (i) first CDI (fCDI), (ii) recurrent CDI (rCDI) and (iii) healthy controls. 16S rRNA sequencing and bile salt metabolomics were performed. Random forest regression models were constructed to predict disease status. PICRUSt analyses were used to test for associations between predicted bacterial bile salt hydrolase (BSH) gene abundances and bile acid levels.
  
  
  
  Sixty patients (20 fCDI, 19 rCDI and 21 controls) were enrolled. Secondary bile acids in stool were significantly elevated in controls compared to rCDI and fCDI (P < 0.0001 and P = 0.0007 respectively). Primary bile acids in stool were significantly elevated in rCDI compared to controls (P < 0.0001) and in rCDI compared to fCDI (P = 0.02). Using random forest regression, we distinguished rCDI and fCDI patients 84.2% of the time using bile acid ratios. Stool deoxycholate to glycoursodeoxycholate ratio was the single best predictor. PICRUSt analyses found significant differences in predicted abundances of bacterial BSH genes in stool samples across the groups.
  
  
  
  Primary and secondary bile acid composition in stool was different in those with rCDI, fCDI and controls. The ratio of stool deoxycholate to glycoursodeoxycholate was the single best predictor of disease state and may be a potential biomarker for recurrence.
authors.affiliation: Division of Gastroenterology, Crohn's and Colitis Center and Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Allegretti
authors.affiliation: Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kearney
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Bogart
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Bullock
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: G K
authors.initials: GK
authors.lastname: Gerber
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Bry
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: C B
authors.initials: CB
authors.lastname: Clish
authors.affiliation: Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Alm
authors.affiliation: Division of Gastroenterology, Crohn's and Colitis Center and Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Korzenik
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000378:metabolism*; D016022:Case-Control Studies; D016360:Clostridioides difficile / Q000235:genetics / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000382:microbiology*; D003430:Cross-Sectional Studies; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics; D064307:Microbiota; D008875:Middle Aged; D012336:RNA, Ribosomal, 16S; D012008:Recurrence
chemical_list: D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D012336:RNA, Ribosomal, 16S