Dihydroxy bile acids increase mucosal permeability and bacterial uptake in human colon biopsies.
OBJECTIVE
Bile acids in mM concentrations are known to increase chloride secretion and alter mucosal permeability in animal colon. Increased mucosal permeability is believed to play an important role in the development of intestinal inflammation. The aim of this study was to investigate the influence of microM concentrations of dihydroxy bile acids on permeability and bacterial uptake in the normal human colon.


METHODS
Endoscopic biopsies from the sigmoid colon of 18 subjects with normal colonic histology were mounted in modified Ussing chambers. Chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) were added to the mucosal compartment. Short-circuit current (Isc) and transepithelial resistance (TER) were studied for 120 min. Cr-EDTA and horseradish peroxidase (HRP) were used to assess paracellular and transcellular permeability, respectively. The transmucosal passage of chemically killed Escherichia coli was quantified and investigated using confocal microscopy.


RESULTS
A significant decrease in TER was seen after 60 min of exposure to 1000 micromol/l CDCA and DCA. The combination of E. coli and 100 micromol/l CDCA gave a decrease in TER compared to controls (p = 0.06). DCA showed a dose-related increase in Cr-EDTA permeability, which was most pronounced at 1000 micromol/l (p = 0.02). Increased E. coli uptake was induced by 500 micromol/l (p = 0.01) and 1000 micromol/l CDCA (p = 0.04). Bacterial uptake was increased at 100 micromol/l by exposure to DCA (p = 0.03). Confocal microscopy revealed the presence of E. coli bacteria in the lamina propria after 15 min of exposure to 1000 micromol/l CDCA and DCA.


CONCLUSIONS
Our study suggests that dihydroxy bile acids in microM concentrations alter barrier function in normal human colon biopsies, causing increased antigen and bacterial uptake; thereby bile acids may contribute to the development of intestinal inflammation.
Münch
Andreas
A
Department of Gastroenterology, UHL, Linköping, Sweden. andreas.munch@lio.se
Ström
Magnus
M
Söderholm
Johan D
JD
D001647:Bile Acids and Salts / Q000494:pharmacology*; D001706:Biopsy; D002463:Cell Membrane Permeability / Q000502:physiology*; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D012809:Colon, Sigmoid / Q000166:cytology / Q000382:microbiology / Q000502:physiology; D003840:Deoxycholic Acid / Q000494:pharmacology; D004594:Electrophysiology; D048168:Escherichia coli K12 / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D018613:Microscopy, Confocal
D001647:Bile Acids and Salts; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid