Pediatric Autoimmune or Primary Sclerosing Cholangitis: Metronidazole Effectiveness on Biochemical Data, Bile Acid Profile, and Gut Microbiota: A Pilot Study

Manon Karemera; Marko Verce; Martin Roumain; Giulio G Muccioli; Patrice D Cani; Amandine Everard; Xavier Stephenne; Etienne Sokal

doi:10.1097/PG9.0000000000000334

Pediatric Autoimmune or Primary Sclerosing Cholangitis: Metronidazole Effectiveness on Biochemical Data, Bile Acid Profile, and Gut Microbiota: A Pilot Study

JPGN Rep. 2023 Jul 17;4(3):e334. doi: 10.1097/PG9.0000000000000334. eCollection 2023 Aug.

Authors

Manon Karemera¹, Marko Verce², Martin Roumain³, Giulio G Muccioli³, Patrice D Cani², Amandine Everard², Xavier Stephenne^{1

4}, Etienne Sokal^{1

4}

Affiliations

¹ From the Department of Pediatrics, Division of Pediatric Gastroenterology and Hepatology, Cliniques universitaires Saint-Luc, Brussels, Belgium.
² Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and Biotechnology (WELBIO), UCLouvain, Université catholique de Louvain, Brussels, Belgium.
³ Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
⁴ UCLouvain, Université catholique de Louvain, Institute of Experimental and Clinical Research - PEDI.

Abstract

Objectives: Autoimmune hepatitis and primary sclerosing cholangitis (PSC) can both be present, resulting in autoimmune sclerosing cholangitis (ASC). PSC physiopathology could be based on the cross-talk between gut microbiota and bile acids (BAs); antibiotics are an innovative therapy. This pilot study assesses metronidazole (MTZ)'s effectiveness in ASC or PSC patients according to the stage of the disease, and its effects on biochemical parameters, BA profiles, and gut microbiota.

Methods: ASC or PSC patients from Cliniques universitaires Saint-Luc's pediatric hepato-gastroenterology division were enrolled retrospectively and prospectively; both datasets were merged. MTZ was administered over at least 14 days on top of standard treatment (ursodeoxycholic acid, azathioprine, and steroids). Fecal and blood samples were collected before (T0) and at MTZ day 14 (T14). Sustained biochemical remission was defined by the reduction of transaminases (AST and ALT), gamma-glutamyl transferase (GGT), and CRP until 12 months post-MTZ.

Results: A total of 18 patients (mean age, 13.2 ± 4.5 years) were enrolled (13 ASC and 5 PSC), and divided in remission or relapse patients. CRP, AST, ALT, and GGT levels decreased post-MTZ in both groups (excepting GGT in relapse patients), with decreases between T0 and T14 being significant for AST and ALT. Relapse patients were older (P = 0.0351) and in late-disease stage, with mainly large-duct PSC (P = 0.0466). In remission patients, the mean plasma relative abundance of hydrophilic BA increased by +6.3% (P = 0.0391) after MTZ. Neither at baseline nor T14, there were significant differences in gut microbiota recorded.

Conclusion: These data are likely indicative of long-term benefits following MTZ therapy at early-stage ASC or PSC, with increased hydrophilic BA abundance. Multicenter prospective studies are needed.

Keywords: autoimmune sclerosing cholangitis; bile acid profile; gut microbiota dysbiosis; metronidazole; overlap syndrome; primary sclerosing cholangitis.

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Publication types

Clinical Trial