Farnesoid X Receptor Expression in Microscopic Colitis: A Potential Role in Disease Etiopathogenesis

Abstract

Introduction: Microscopic colitis (MC) is a chronic inflammatory bowel disease with unclear etiology. Bile acid (BA) malabsorption has been described in MC patients. Farnesoid X receptor (FXR) is the main BA receptor; FXR-mediated mechanisms prevent the noxious effects of BA accumulation, preserving the integrity of the intestinal epithelial barrier and preventing intestinal inflammation. Aim: Our aim was to describe the expression of FXR in patients with MC. Methods: Archival formalin-fixed paraffin-embedded samples from the terminal ileum, right and left colon were obtained from patients with MC and matched controls. Immunohistochemistry was performed and nuclear FXR expression scored in a semi-quantitative way. Results: 169 formalin-fixed paraffin-embedded samples from 35 patients with MC and 31 controls were retrieved. There was a significant reduction of FXR expression in patients with MC versus controls both in the right colon (moderate-strong FXR expression: 21.1 vs. 64.3%; p = 0.003) and left colon (moderate-strong FXR expression: 8.3 vs. 38.7%; p = 0.027). No significant differences in FXR expression were observed in the ileum of patients with MC (moderate-strong FXR expression: 76.9 vs. 90.9%; p = 0.5). We found no difference in FXR expression between the two types of MC. No association between the degree of lymphocyte infiltration or the thickness of collagen band and FXR expression was found. Conclusions: Patients with MC present a significantly lower expression of FXR in the colon. This could render colonic epithelial cells more susceptible to the deleterious effects of BA, contributing to disease pathogenesis and symptoms in MC.

Medication use and microscopic colitis

“…The mechanism could be related to the farnesoid X receptor (FXR). FXR acts as the main nuclear bile acid receptor playing a role in bile acid synthesis and intracellular bile acid accumulation 38 . Patients with microscopic colitis have been found to have significant reductions in FXR expression in the colon, possibly making the colonic epithelial cells more susceptible to bile acids and contributing to disease pathogenesis and symptoms 38 .…”

“…FXR acts as the main nuclear bile acid receptor playing a role in bile acid synthesis and intracellular bile acid accumulation 38 . Patients with microscopic colitis have been found to have significant reductions in FXR expression in the colon, possibly making the colonic epithelial cells more susceptible to bile acids and contributing to disease pathogenesis and symptoms 38 . Our results provide further support for the belief that patients with microscopic colitis may be particularly susceptible to bile acids or that bile acids may have an etiologic role.…”

Fecal Microbiota of Diarrhea-Predominant Irritable Bowel Syndrome Patients Causes Hepatic Inflammation of Germ-Free Rats and Berberine Reverses It Partially

“…These alterations might suggest high availability of these substances in the host and increased antioxidation activity, which may provide protection from oxidative stress and result in decreased serum. FXR-mediated mechanisms prevent the noxious effects of BA accumulation, thus preserving the integrity of the intestinal epithelial barrier and preventing intestinal inflammation [29]. In the liver, FXR has been considered a multifunctional cell protector and tumor suppressor, and it can promote liver regeneration and repair after injury [30].…”

European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations

“…Whether this bile acid diarrhoea is a consequence of inflammation in the right colon or even terminal ileum or merely a coexisting disease per se remains to be explored. Expression of the main bile acid receptor was reduced in biopsies from the colon of patients with MC 295 . MC was not associated with prior cholecystectomy 296 …”

“…LE: low; GR: NA; agreement: 83%, consensus. Expression of the main bile acid receptor was reduced in biopsies from the colon of patients with MC 295. MC was not associated with prior cholecystectomy 296.…”