TY - JOUR
T1 - Liver steatosis induced by small bowel resection is prevented by oral vancomycin
AU - Barron, Lauren K.
AU - Gayer, Christopher P.
AU - Roberts, Anne
AU - Golden, Jamie M.
AU - Aladegbami, Bola G.
AU - Guo, Jun
AU - Erwin, Christopher R.
AU - Warner, Brad W.
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Background Intestinal failure–associated liver disease causes significant mortality in patients with short bowel syndrome. Steatosis, a major component of intestinal failure–associated liver disease has been shown to persist even after weaning from parenteral nutrition. We sought to determine whether steatosis occurs in our murine model of short bowel syndrome and whether steatosis was affected by manipulation of the intestinal microbiome. Methods Male C57BL6 mice underwent 50% small bowel resection and orogastric gavage with vancomycin or vehicle for 10 weeks. DNA was extracted from stool samples then sequenced using 16s rRNA. Liver lipid content was analyzed. Bile acids were measured in liver and stool. Results Compared with unoperated mice, small bowel resection resulted in significant changes in the fecal microbiome and was associated with a >25-fold increase in steatosis. Oral vancomycin profoundly altered the gut microbiome and was associated with a 15-fold reduction in hepatic lipid content after resection. There was a 17-fold reduction in fecal secondary bile acids after vancomycin treatment. Conclusion Massive small bowel resection in mice is associated with development of steatosis and prevented by oral vancomycin. These findings implicate a critical role for gut bacteria in intestinal failure–associated liver disease pathogenesis and illuminate a novel, operative model for future investigation into this important morbidity.
AB - Background Intestinal failure–associated liver disease causes significant mortality in patients with short bowel syndrome. Steatosis, a major component of intestinal failure–associated liver disease has been shown to persist even after weaning from parenteral nutrition. We sought to determine whether steatosis occurs in our murine model of short bowel syndrome and whether steatosis was affected by manipulation of the intestinal microbiome. Methods Male C57BL6 mice underwent 50% small bowel resection and orogastric gavage with vancomycin or vehicle for 10 weeks. DNA was extracted from stool samples then sequenced using 16s rRNA. Liver lipid content was analyzed. Bile acids were measured in liver and stool. Results Compared with unoperated mice, small bowel resection resulted in significant changes in the fecal microbiome and was associated with a >25-fold increase in steatosis. Oral vancomycin profoundly altered the gut microbiome and was associated with a 15-fold reduction in hepatic lipid content after resection. There was a 17-fold reduction in fecal secondary bile acids after vancomycin treatment. Conclusion Massive small bowel resection in mice is associated with development of steatosis and prevented by oral vancomycin. These findings implicate a critical role for gut bacteria in intestinal failure–associated liver disease pathogenesis and illuminate a novel, operative model for future investigation into this important morbidity.
UR - http://www.scopus.com/inward/record.url?scp=84997218193&partnerID=8YFLogxK
U2 - 10.1016/j.surg.2016.07.018
DO - 10.1016/j.surg.2016.07.018
M3 - Article
C2 - 27592213
AN - SCOPUS:84997218193
SN - 0039-6060
VL - 160
SP - 1485
EP - 1495
JO - Surgery (United States)
JF - Surgery (United States)
IS - 6
ER -