Low levels of bile acids increase bacterial uptake in colonic biopsies from patients with collagenous colitis in remission

• Published in: Alimentary pharmacology & therapeutics Vol. 33; no. 8; pp. 954 - 960
• Main Authors: Münch, A., Söderholm, J. D., Öst, Å., Carlsson, A. H., Magnusson, K.‐E., Ström, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2011; Blackwell
• Subjects: Acids; Adult; Aged; Aged, 80 and over; Bile acids; Bile Acids and Salts - pharmacology; Biological and medical sciences; Biological Transport; Biopsy; budesonide; Budesonide - therapeutic use; Case-Control Studies; Chenodeoxycholic Acid - pharmacology; Chenodiol; Colitis; Colitis, Collagenous - metabolism; Colitis, Collagenous - microbiology; Colitis, Collagenous - pathology; Collagen; Colon; Confocal microscopy; Deoxycholic acid; Deoxycholic Acid - pharmacology; Digestive system; Escherichia coli; Escherichia coli K12 - metabolism; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal Agents - administration & dosage; Humans; In Vitro Techniques; Inflammation; Malabsorption; Male; Medical sciences; MEDICIN; MEDICINE; Microscopy, Confocal; Middle Aged; Mucosa; Other diseases. Semiology; Pharmacology. Drug treatments; Remission; Short-circuit current; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Human; Collagenous colitis; Digestive system; Gut; Uptake; Infection; Anatomic pathology; Biopsy; Bile acid; Bacteriosis; Digestive diseases; Intestinal disease; Bacteria; Remission; Colon
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2011.04611.x

Aliment Pharmacol Ther 2011; 33: 954–960 Summary Background  Patients with collagenous colitis have an impaired mucosal barrier. Moreover, collagenous colitis is associated with bile acid malabsorption. Bile acids can increase bacterial mucosal uptake in humans. Mucosal barrier function was investigated by exposing colonic biopsies to chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA) in Ussing chamber experiments. Aim  To find if low levels of bile acids increase bacterial uptake in colonic biopsies from collagenous colitis patients. Methods  The study comprised 33 individuals; 25 with collagenous colitis (14 in clinical remission without treatment, 11 with active disease and 10 examined in clinical remission resulting from treatment with 6 mg budesonide); eight healthy individuals undergoing screening colonoscopy served as controls. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short‐circuit current (Isc), potential difference, trans‐epithelial resistance and transmucosal passage of Escherichia coli K12 after adding 100 μmol/L CDCA or DCA. Results  When adding 100 μmol/L CDCA or DCA, bacterial uptake increased fourfold in biopsies of patients in remission; CDCA 6.5 units [2.5–9.8] and DCA 6.2 units [2.1–22] (median [IQR]), compared with uptake in biopsies without added bile acids 1.6 units [1.1–3] (P = 0.004 and P = 0.01 respectively). In active disease and in patients in remission due to budesonide treatment, bile acids did not affect bacterial uptake. Confocal microscopy revealed trans‐epithelial passage of E. coli K12 within 30 min. Conclusions  Low concentrations of dihydroxy‐bile acids exacerbate mucosal barrier dysfunction in colonic biopsies of patients with collagenous colitis in remission. This allows a substantially increased bacterial uptake, which may contribute to recurrence of inflammation.