High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids

World J Gastroenterol. 2012 Mar 7;18(9):923-9. doi: 10.3748/wjg.v18.i9.923.


Aim: To investigate whether high-fat-feeding is associated with increased intestinal permeability via alterations in bile acid metabolism.

Methods: Male C57Bl/6J mice were fed on a high-fat (n = 26) or low-fat diet (n = 24) for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile acids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis factor (TNF).

Results: Intestinal permeability was significantly increased by high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat, P = 0.03) and colon (0.335 for control vs 0.433 for high-fat, P = 0.01), but not in duodenum or ileum. The concentration of nearly all identified bile acids was significantly increased by high-fat feeding (P < 0.001). The proportion of ursodeoxycholic acid (UDCA) in all bile acids was decreased (1.4% ± 0.1% in high-fat vs 2.8% ± 0.3% in controls, P < 0.01) and correlated inversely with intestinal permeability (r = -0.72, P = 0.01). High-fat feeding also increased jejunal FXR expression, as well as TNF expression along the intestine, especially in the colon.

Conclusion: High-fat-feeding increased intestinal permeability, perhaps by a mechanism related to bile acid metabolism, namely a decreased proportion of fecal UDCA and increased FXR expression.

Keywords: Bile acids; Bile salts; Diet-induced obesity; Farnesoid X-activated receptor; Intestinal permeability; Ursodeoxycholic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Acids and Salts / chemistry
  • Bile Acids and Salts / metabolism*
  • Diet, Fat-Restricted
  • Diet, High-Fat / adverse effects*
  • Feces / chemistry*
  • Intestines / anatomy & histology
  • Intestines / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Permeability
  • Random Allocation
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Ursodeoxycholic Acid / chemistry
  • Ursodeoxycholic Acid / metabolism


  • Bile Acids and Salts
  • Receptors, Cytoplasmic and Nuclear
  • Tumor Necrosis Factor-alpha
  • farnesoid X-activated receptor
  • Ursodeoxycholic Acid