Abstract

Inflammatory bowel disease (IBD) causes chronic inflammation affecting the GI tract. It is classified as consisting of Crohn’s Disease (CD) and Ulcerative Colitis (UC). Bile Acid absorption is altered in both pre-clinical models of Inflammatory Bowel Disease (IB) and in human IBD. The bile acid transporter apical sodium dependent bile acid transporter (ASBT) showed decreased expression in rats with TNBS colitis. Decreased ASBT expression has also been described in murine, canine and rabbit models of intestinal inflammation. Human IBD studies have shown that an inflamed ileum can interrupt enterohepatic recirculation of bile acid, which could be due to inflammatory cytokine induced repression of the ASBT promoter. There are different hypotheses as to why ASBT is downregulated during CD. In addition, one study has demonstrated the beneficial effect of a glucocorticoid on ASBT expression, when treating IBD. Our aim in this paper was to systematically review various aspects of bile acid malabsorption in animal models of intestinal inflammation, as well as in IBD.

Highlights

  • Increased fecal bile acid excretion (32%) Not measured Decreased uptake of bile acid et al showed that intracolonic administration of deoxycholic acid (DCA) worsened murine Dextran Sulfate Sodium (DSS)-induced colitis

  • Using a post hoc analysis comparing colesevelam alone, cholestyramine alone, loperamide alone, and colesevelam with loperamide; the results suggested colesevelam was an effective treatment for post-operative bile acid malabsorption (BAM) in Crohn’s Disease (CD) compared to other options (Devarakonda et al, 2019; Valencia-Rodríguez et al, 2019)

  • Type 1 BAM is a neglected and underdiagnosed symptom of CD, which has led to many cases of diarrhea due to bile acid spillover into the colon

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Summary

BILE ACID SYNTHESIS AND ABSORPTION IN HUMANS AND RODENTS

The end product of cholesterol catabolism, is synthesized in the liver through multiple oxidation and hydroxylation mechanisms (Dietschy, 1968; Dawson and Karpen, 2015). The intracolonic administration of Trinitrobenzene Sulfonic Acid (TNBS) to rodents (rats, mice) is a commonly used model of CD (Te Velde et al, 2006; Fitzpatrick et al, 2012; Hou et al, 2018; Fitzpatrick et al, 2020) Using this model, investigators showed decreased expression of intestinal ASBT primarily during the acute phase of the colitis (Hou et al, 2018). The investigators emphasized that this ileitis model was a more appropriate animal model of IBD to study alterations in bile acid transporters, because >95% of the intestinal bile acid pool does not transit to the colon due to typically efficient reabsorption in the distal ileum (van den Bossche et al, 2017).

Decreased fecal secondary bile acids
CLINICAL OBSERVATIONS
BILE ACID TRANSPORTERS IN IBD
IBD type
BAM DIAGNOSIS
Findings
SUMMARY
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