title: Modulation of the fecal bile acid profile by gut microbiota in cirrhosis.
abstract: OBJECTIVE
  The 7α-dehydroxylation of primary bile acids (BAs), chenodeoxycholic (CDCA) and cholic acid (CA) into the secondary BAs, lithocholic (LCA) and deoxycholic acid (DCA), is a key function of the gut microbiota. We aimed at studying the linkage between fecal BAs and gut microbiota in cirrhosis since this could help understand cirrhosis progression.
  
  
  METHODS
  Fecal microbiota were analyzed by culture-independent multitagged-pyrosequencing, fecal BAs using HPLC and serum BAs using LC-MS in controls, early (Child A) and advanced cirrhotics (Child B/C). A subgroup of early cirrhotics underwent BA and microbiota analysis before/after eight weeks of rifaximin.
  
  
  RESULTS
  Cross-sectional: 47 cirrhotics (24 advanced) and 14 controls were included. In feces, advanced cirrhotics had the lowest total, secondary, secondary/primary BA ratios, and the highest primary BAs compared to early cirrhotics and controls. Secondary fecal BAs were detectable in all controls but in a significantly lower proportion of cirrhotics (p<0.002). Serum primary BAs were higher in advanced cirrhotics compared to the rest. Cirrhotics, compared to controls, had a higher Enterobacteriaceae (potentially pathogenic) but lower Lachonospiraceae, Ruminococcaceae and Blautia (7α-dehydroxylating bacteria) abundance. CDCA was positively correlated with Enterobacteriaceae (r=0.57, p<0.008) while Ruminococcaceae were positively correlated with DCA (r=0.4, p<0.05). A positive correlation between Ruminococcaceae and DCA/CA (r=0.82, p<0.012) and Blautia with LCA/CDCA (r=0.61, p<0.03) was also seen. Prospective study: post-rifaximin, six early cirrhotics had reduction in Veillonellaceae and in secondary/primary BA ratios.
  
  
  CONCLUSIONS
  Cirrhosis, especially advanced disease, is associated with a decreased conversion of primary to secondary fecal BAs, which is linked to abundance of key gut microbiome taxa.
authors: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA 23249, United States.
authors: Genta
authors: G
authors: Kakiyama
authors: William M
authors: WM
authors: Pandak
authors: Patrick M
authors: PM
authors: Gillevet
authors: Phillip B
authors: PB
authors: Hylemon
authors: Douglas M
authors: DM
authors: Heuman
authors: Kalyani
authors: K
authors: Daita
authors: Hajime
authors: H
authors: Takei
authors: Akina
authors: A
authors: Muto
authors: Hiroshi
authors: H
authors: Nittono
authors: Jason M
authors: JM
authors: Ridlon
authors: Melanie B
authors: MB
authors: White
authors: Nicole A
authors: NA
authors: Noble
authors: Pamela
authors: P
authors: Monteith
authors: Michael
authors: M
authors: Fuchs
authors: Leroy R
authors: LR
authors: Thacker
authors: Masoumeh
authors: M
authors: Sikaroodi
authors: Jasmohan S
authors: JS
authors: Bajaj
mesh_terms: D000890:Anti-Infective Agents / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000032:analysis*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004755:Enterobacteriaceae / Q000302:isolation & purification / Q000502:physiology; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D064307:Microbiota / Q000502:physiology*; D008875:Middle Aged; D011446:Prospective Studies; D012294:Rifamycins / Q000627:therapeutic use; D000078262:Rifaximin; D045857:Ruminococcus / Q000302:isolation & purification / Q000502:physiology; D045854:Veillonellaceae / Q000302:isolation & purification / Q000502:physiology
chemical_list: D000890:Anti-Infective Agents; D001647:Bile Acids and Salts; D012294:Rifamycins; D000078262:Rifaximin