Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2023; 29(5): 851-866
Published online Feb 7, 2023. doi: 10.3748/wjg.v29.i5.851
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.
Data sharing statement: The dataset is available from the corresponding author at caroline.valibouze@chu-lille.fr.
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
Abstract
BACKGROUND

Postoperative recurrence (POR) after ileocecal resection (ICR) affects most Crohn's disease patients within 3-5 years after surgery. Adherent-invasive Escherichia coli (AIEC) typified by the LF82 strain are pathobionts that are frequently detected in POR of Crohn's disease and have a potential role in the early stages of the disease pathogenesis. Saccharomyces cerevisiae CNCM I-3856 is a probiotic yeast reported to inhibit AIEC adhesion to intestinal epithelial cells and to favor their elimination from the gut.

AIM

To evaluate the efficacy of CNCM I-3856 in preventing POR induced by LF82 in an HLA-B27 transgenic (TgB27) rat model.

METHODS

Sixty-four rats [strain F344, 38 TgB27, 26 control non-Tg (nTg)] underwent an ICR at the 12th wk (W12) of life and were sacrificed at the 18th wk (W18) of life. TgB27 rats were challenged daily with oral administration of LF82 (109 colony forming units (CFUs)/day (d), n = 8), PBS (n = 5), CNCM I-3856 (109 CFUs/d, n = 7) or a combination of LF82 and CNCM I-3856 (n = 18). nTg rats receiving LF82 (n = 5), PBS (n = 5), CNCM I-3856 (n = 7) or CNCM I-3856 and LF82 (n = 9) under the same conditions were used as controls. POR was analyzed using macroscopic (from 0 to 4) and histologic (from 0 to 6) scores. Luminal LF82 quantifications were performed weekly for each animal. Adherent LF82 and inflammatory/regulatory cytokines were quantified in biopsies at W12 and W18. Data are expressed as the median with the interquartile range.

RESULTS

nTg animals did not develop POR. A total of 7/8 (87%) of the TgB27 rats receiving LF82 alone had POR (macroscopic score ≥ 2), which was significantly prevented by CNCM I-3856 administration [6/18 (33%) TgB27 rats, P = 0.01]. Macroscopic lesions were located 2 cm above the anastomosis in the TgB27 rats receiving LF82 alone and consisted of ulcerations with a score of 3.5 (2 - 4). Seven out of 18 TgB27 rats (39%) receiving CNCM I-3856 and LF82 had no macroscopic lesions. Compared to untreated TgB27 animals receiving LF82 alone, coadministration of CNCM I-3856 and LF82 significantly reduced the macroscopic [3.5 (2 - 4) vs 1 (0 - 3), P = 0.002] and histological lesions by more than 50% [4.5 (3.3 - 5.8) vs 2 (1.3 - 3), P = 0.003]. The levels of adherent LF82 were correlated with anastomotic macroscopic scores in TgB27 rats (r = 0.49, P = 0.006), with a higher risk of POR in animals having high levels of luminal LF82 (71.4% vs 25%, P = 0.02). Administration of CNCM I-3856 significantly reduced the levels of luminal and adherent LF82, increased the production of interleukin (IL)-10 and decreased the production of IL-23 and IL-17 in TgB27 rats.

CONCLUSION

In a reliable model of POR induced by LF82 in TgB27 rats, CNCM I-3856 prevents macroscopic POR by decreasing LF82 infection and gut inflammation.

Keywords: Crohn's disease; Recurrence; Escherichia coli; Probiotic; Saccharomyces cerevisiae; Colorectal surgery

Core Tip: Gut dysbiosis plays a main role in the postoperative recurrence (POR) of Crohn's disease (CD). CD dysbiosis is characterized by a lower microbiota diversity with an increase in pathogenic species. Among them, adherent-invasive Escherichia coli (AIEC) has been linked to POR. Saccharomyces cerevisiae (S. cerevisiae) CNCM I-3856 is a probiotic yeast that specifically targets AIEC by preventing the bacterial adhesion process and inhibiting its persistence within the bowel. This study confirmed the capacity of S. cerevisiae CNCM I-3856 to prevent AIEC-induced POR by decreasing the infection in a transgenic HLA-B27 rat model of POR after ileocecal resection.