An Analysis of the Role of the Indigenous Microbiota in Cholesterol Gallstone Pathogenesis
Name
Fremont-Rahl-2013-An analysis of the r.pdf
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Author(s)
Fremont-Rahl, Jacqueline J.
Ge, Zhongming
Umana, Carlos
Whary, Mark T.
Taylor, Nancy S.
Muthupalani, Sureshkumar
Carey, Martin C.
Fox, James G.
Maurer, Kirk J.
Date Issued
July 2013
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Fremont-Rahl, Jacqueline J., Zhongming Ge, Carlos Umana, Mark T. Whary, Nancy S. Taylor, Sureshkumar Muthupalani, Martin C. Carey, James G. Fox, and Kirk J. Maurer. “An Analysis of the Role of the Indigenous Microbiota in Cholesterol Gallstone Pathogenesis.” Edited by Georgina L. Hold. PLoS ONE 8, no. 7 (July 29, 2013): e70657.
Version
Final published version
Abstract
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 <1day 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Division of Comparative Medicine
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0070657
