Altered jejunal macromolecular barrier induced by alpha-dihydroxy deconjugated bile salts

The effect of deconjugated bile salt hydroxy group position and numbers on the ability of these agents to alter the normal lumen-to-blood jejunal barrier to intact protein penetration was analyzed. Only in vivo jejunal perfusion with 0.5 mM alpha-dihydroxy deconjugated bile salts chenodeoxycholate and deoxycholate led to increased penetration of the 40,000-molecular-weight protein horseradish peroxidase (HRP). This increased absorption of HRP with 0.5 mM chenodeoxycholate and deoxycholate was detectable biochemically, as well as by light and electron microscopic cytochemistry, and occurred in the absence of demonstrable histological or ultrastructural damage to the epithelium. Conjugation of chenodeoxycholate with glycine, epimerization of chenodeoxycholate from 7 alpha-hydroxy to 7 beta-hydroxy as in ursodeoxycholate, or addition of a third hydroxyl group as in cholate all eliminated the increase in jejunal HRP penetration and led to HRP absorption levels like those in bile salt-free preparations. The effect of chenodeoxycholate and deoxycholate on HRP absorption was paralleled by their production of net jejunal water secretion. The observations suggest that the naturally occurring alpha-dihydroxy bile salts may lead to an increase in intact antigen or toxin absorption during bacterial stasis syndromes.