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Publication : An analysis of the role of the indigenous microbiota in cholesterol gallstone pathogenesis.

First Author  Fremont-Rahl JJ Year  2013
Journal  PLoS One Volume  8
Issue  7 Pages  e70657
PubMed ID  23923015 Mgi Jnum  J:301946
Mgi Id  MGI:6238465 Doi  10.1371/journal.pone.0070657
Citation  Fremont-Rahl JJ, et al. (2013) An analysis of the role of the indigenous microbiota in cholesterol gallstone pathogenesis. PLoS One 8(7):e70657
abstractText  BACKGROUND AND AIMS: Cholesterol gallstone disease is a complex process involving both genetic and environmental variables. No information exists regarding what role if any the indigenous gastrointestinal microbiota may play in cholesterol gallstone pathogenesis and whether variations in the microbiota can alter cholesterol gallstone prevalence rates. METHODS: Genetically related substrains (BALB/cJ and BALB/cJBomTac) and (BALB/AnNTac and BALB/cByJ) of mice obtained from different vendors were compared for cholesterol gallstone prevalence after being fed a lithogenic diet for 8 weeks. The indigenous microbiome was altered in these substrains by oral gavage of fecal slurries as adults, by cross-fostering to mice with divergent flora at <1 day of age or by rederiving into a germ-free state. RESULTS: Alterations in the indigenous microbiome altered significantly the accumulation of mucin gel and normalized gallbladder weight but did not alter cholesterol gallstone susceptibility in conventionally housed SPF mice. Germ-free rederivation rendered mice more susceptible to cholesterol gallstone formation. This susceptibility appeared to be largely due to alterations in gallbladder size and gallbladder wall inflammation. Colonization of germ-free mice with members of altered Schaedler flora normalized the gallstone phenotype to a level similar to conventionally housed mice. CONCLUSIONS: These data demonstrate that alterations in the gastrointestinal microbiome may alter aspects of cholesterol gallstone pathogenesis and that in the appropriate circumstances these changes may impact cholesterol cholelithogenesis.
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