Effect of short chain fatty acids on paracellular permeability in
the caco-2 model of intestinal epithelium.
Mariadason, John M., David H. Barkla, Peter R. Gibson.
UNIVERSITY OF MELBOURNE DEPARTMENT OF MEDICINE, THE ROYAL MELBOURNE
HOSPITAL, and MONASH UNIVERSITY, DEPARTMENT OF ANATOMY, VICTORIA,
AUSTRALIA
APStracts 3:0215G, 1996.
Control of paracellular permeability in the colonic epithelium is
fundamental to its functional competence. This study examines the
relationship between physiologically relevant short chain fatty acids
(SCFAs) and paracellular permeability using the Caco-2 cell line
model. Butyrate induced a concentration dependent, reversible
increase in trans-epithelial resistance (TER), that was maximal after
72 hours. Butyrate (2 mM) increased TER by 299 +/- 69% (mean +/- sem,
n=5, P<0.05, t test) and reduced mannitol flux to 52 +/- 11%
(P<0.05) of control. The effect of butyrate was dependent upon
protein synthesis and gene transcription, but not dependent on its
oxidation or activation of cAMP. The other SCFAs propionate and
acetate, also induced a concentration dependent increase in TER.
Butyrate's effect parallelled changes in cellular differentiation as
alkaline phosphatase activity, carcinoembryonic antigen expression
(CEA), and dome formation were increased. Furthermore, other
differentiating agents (DMSO and retinoic acid) also increased TER.
Thus, SCFAs reduce paracellular permeability in the Caco-2 cell line,
possibly by promotion of a more differentiated phenotype. If such an
effect occurs in vivo it may have ramifications for the biology and
pathobiology of colonic mucosa.
Received 28 February 1996; accepted in final form 26 September
1996.
APS Manuscript Number G77-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996