Systemic effects of acute terminal ileitis on uninflamed gut aggravate bile acid malabsorption

Some patients with terminal ileitis suffer from significant bile acid malabsorption even if the inflammation is locally limited. We hypothesized that inflammation in the terminal ileum may lead to changes in mucosal absorption in more proximal intestinal segments and aggravate bile acid malabsorption.

Five hamsters underwent laparotomy and localized instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in 10% ethanol into the last 4 cm of ileum to create terminal ileitis. A control group (n = 5) underwent instillation of saline. Animals were sacrificed after 24 h. Active and passive transport of radiolabeled bile acids was measured in the proximal and terminal ileum and glucose absorption in the jejunum using an everted sleeve technique. Myeloperoxidase (MPO) activity and histomorphology were examined by standard methods.

In animals with ileitis, active bile acid uptake decreased by 84% in the terminal ileum (t test, P <0.001) and by 58% in the proximal ileum (P < 0.05) compared with saline-treated controls. Jejunal glucose absorption decreased by 59% (P < 0.01). Passive bile acid and glucose absorption rates were not significantly changed in any segments of treated animals versus controls. Histological examination of the treated group revealed signs of acute terminal ileitis without changes in the proximal ileum and jejunum. All control tissues were uninflamed. MPO activity was 13-fold increased in the inflamed ileal samples compared with controls (P <0.001). No significant changes were seen in the proximal ileum and jejunum. There was no evidence of reflux of TNBS into proximal ileum. Nominal mucosal surface area values showed no significant changes between groups. Pretreatment of an additional group of hamsters (n = 5) with acetylsalicylic acid before TNBS instillation ameliorated the inflammatory response in the terminal ileum and largely abrogated the negative effects on ileal bile acid absorption.

These data suggest that limited acute ileitis impairs active bile acid uptake in the terminal ileum. It also diminishes active bile acid and glucose absorption in more proximal segments of the small intestine, likely by a systemic effect. This systemic effect may aggravate bile acid malabsorption in patients with limited ileitis.