Copyright
©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Saccharomyces cerevisiae prevents postoperative recurrence of Crohn's disease modeled by ileocecal resection in HLA-B27 transgenic rats
Caroline Valibouze, Silvia Speca, Caroline Dubuquoy, Florian Mourey, Lena M'Ba, Lucil Schneider, Marie Titecat, Benoît Foligné, Michaël Genin, Christel Neut, Philippe Zerbib, Pierre Desreumaux
Caroline Valibouze, Lena M'Ba, Lucil Schneider, Philippe Zerbib, Department of Digestive Surgery and Transplantation, Lille University Hospital, Lille 59037, France
Caroline Valibouze, Silvia Speca, Marie Titecat, Benoît Foligné, Christel Neut, Philippe Zerbib, Pierre Desreumaux, U1286 - INFINITE - Institute for Translational Research in Inflammation, Univ. Lille, Inserm, CHU Lille, Lille 59000, France
Caroline Dubuquoy, Intestinal Biotech Development, Lille 59045, France
Florian Mourey, Department of Research and Applications, Gnosis by Lesaffre, Lesaffre Group, Marcq-en-Baroeul 59700, France
Michaël Genin, ULR 2694 - METRICS: Évaluation des Technologies de Santé et des Pratiques Médicales, University of Lille, Lille University Hospital, Lille 59000, France
Pierre Desreumaux, Department of Hepato-Gastroenterology, Lille University Hospital, Lille 59037, France
Author contributions: Desreumaux P, Dubuquoy C and Valibouze C designed the study; Valibouze C, Dubuquoy C, M’Ba L, Schneider L and Neut C acquired the data; Genin M supervised the statistical analysis; all authors interpreted the data; Valibouze C and Desreumaux P drafted the article; All authors critically reviewed the manuscript and approved the final version for submission.
Institutional review board statement: Experiments were realized at the Institute Pasteur of Lille, according to the European directive 2016/63/UE enforced by decree No. 2013-118 under the number D 59 350 009.
Institutional animal care and use committee statement: Animal experiments were authorized by the departmental ethics committee (No. CEEA 01292-01).
Conflict-of-interest statement: Mourey F is an employee of Lesaffre. Desreumaux P reports personal fees from Abbvie, personal fees from Abbott, personal fees from Amgen, personal fees from Biocodex, personal fees from Biofortis, personal fees from Biogen, personal fees from Biokuris, personal fees from Ferring, personal fees from Fresenius, personal fees from Janssen, personal fees from Kitozyme, personal fees from Lesaffre, personal fees from MSD, personal fees from Norgine, personal fees from Pfizer, personal fees from Sandoz, personal fees from Shire, personal fees from Takeda, personal fees from Tillotts, and personal fees from UCB, outside of the submitted work. In addition, Dr. Desreumaux has a patent (WO2009103884) issued. All other authors have nothing to disclose.
ARRIVE guidelines statement: The authors read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Caroline Valibouze, MD, Surgeon, Department of Digestive Surgery and Transplantation, Lille University Hospital, Rue Michel Polonovski, Lille 59037, France.
caroline.valibouze@chu-lille.fr
Received: September 25, 2022
Peer-review started: September 25, 2022
First decision: November 5, 2022
Revised: November 16, 2022
Accepted: December 13, 2022
Article in press: December 13, 2022
Published online: February 7, 2023
Processing time: 134 Days and 1.4 Hours
ARTICLE HIGHLIGHTS
Research background
The presence of adherent-invasive Escherichia coli (AIEC) in intestinal flora is associated with postoperative recurrence (POR) of crohn's disease (CD). Saccharomyces cerevisiae (S. cerevisiae) CNCM I-3856 is a safe and effective probiotic yeast that has already been evaluated in randomized placebo-controlled studies in patients with irritable bowel syndrome. Preclinical studies demonstrate the capacity of S. cerevisiae CNCM I-3856 to agglutinate invasive Escherichia coli strains and to prevent their adhesion to intestinal epithelial cells, favoring AIEC elimination from the gut of mice.
Research motivation
To demonstrate that S. cerevisiae CNCM I-3856 should be considered as a postoperative prophylactic medical therapy in CD patients harboring AIEC bacteria.
Research objectives
To evaluate the beneficial effect of S. cerevisiae CNCM I-3856 and its mechanisms of action in preventing AIEC-induced POR in an HLA-B27 transgenic (TgB27) rat model of CD.
Research methods
TgB27 and control rats underwent an ileocecal resection at the 12th wk of life and sacrificed 6 wk later to assess POR using macroscopic and histological scores and quantification of mucosal inflammatory/ regulatory cytokines. Animals were challenged daily with an oral administration of AIEC and were treated orally with S. cerevisiae CNCM I-3856 (109 colony forming units/day). Luminal and adherent AIEC were regularly quantified throughout the duration of the study.
Research results
Eighty-seven percent of TgB27 rats developed POR characterized by anastomotic macroscopic ulcerations, transparietal neutrophil infiltration and a shift in the cytokine profile toward the interleukin (IL)-17/IL-23 axis. Oral administration of S. cerevisiae CNCM I-3856 reduced this POR by more than 60%, increased AIEC elimination from the gut, induced intestinal IL-10 production and restored the local upregulation of IL-17/IL-23. A high concentration of AIEC quantified in the stool of rats after surgery had a 70% positive predictive value for POR occurring 4 wk later.
Research conclusions
Ileocecal resection in TgB27 rats is a novel, useful, reliable model mimicking POR of CD and aided the discovery of new therapeutic targets. Oral administration of S. cerevisiae CNCM I-3856 safely prevented POR of CD through AIEC decolonization and immunomodulatory/anti-inflammatory capacities.
Research perspectives
The probiotic S. cerevisiae CNCM I-3856, which is already an alternative solution for the management of patients with irritable bowel syndrome to improve abdominal pain and quality of life, should represent a promising prophylactic natural nonchemotherapeutic solution in the management of postoperative CD. Monitoring AIEC levels in stool after surgery for CD should be considered as a companion test to identify patients at high risk of POR and to monitor treatment response.
