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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet
Juan Pablo Stefanolo, Verónica Segura, Martina Grizzuti, Abel Heredia, Isabel Comino, Ana Florencia Costa, Roberto Puebla, María Paz Temprano, Sonia Isabel Niveloni, Gabriel de Diego, María E Oregui, Edgardo Gustavo Smecuol, Mauricio C de Marzi, Elena F Verdú, Carolina Sousa, Julio César Bai
Juan Pablo Stefanolo, Roberto Puebla, María Paz Temprano, Sonia Isabel Niveloni, Edgardo Gustavo Smecuol, Small Bowel Section, Department of Medicine, Gastroenterology Hospital of Buenos Aires “Dr. C. Bonorino Udaondo”, Buenos Aires 1264, Argentina
Verónica Segura, Abel Heredia, Isabel Comino, Carolina Sousa, Department of Microbiology and Parasitology, Faculty of Pharmacy, University of Seville, Seville 41080, Spain
Martina Grizzuti, Ana Florencia Costa, María E Oregui, Julio César Bai, Department of Medicine, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires 1264, Argentina
Gabriel de Diego, Mauricio C de Marzi, Basic and Applied Research Group in Immunology and Bioactives (GIBAIB), Institute of Ecology and Sustainable Development (INEDES), National University of Lujan, Luján 6700, Buenos Aires, Argentina
Elena F Verdú, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton L8S 4L8, Ontario, Canada
Julio César Bai, Facultad de Medicina, Universidad del Salvador, Buenos Aires C1051ABB, Argentina
Author contributions: Stefanolo JP contributed to the study’s design, collected the patients, performed statistical analysis of the data and critical review of the manuscript; Segura V, Heredia A, and Comino I performed the gluten immunogenic peptides stool tests; Grizutti M, Costa AF, and Oregui ME collected the patients and performed data acquisition; Temprano MP performed the dietary assessment; Puebla R, de Diego G, and de Marzi MC produced the biochemical determinations and performed the serology; Niveloni SI and Smecuol EG contributed to the data acquisition; Bai JC planned the study; Bai JC, Verdú EF, and Sousa C contributed to the study design, data analysis, and writing of the manuscript; All authors read and approved the final manuscript.
Supported by the Asociación de Celíacos y Sensibles al Gluten de Madrid, No. ACM2020); and Research Committee Argentine Society of Gastroenterology, No. 2020.
Institutional review board statement: The study was reviewed and approved by Dr. C. Bonorino Udaondo Gastroenterology Hospital’s institutional ethical committee (CEI) and the local research committee (CODEI).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Clinical trial registration statement: The study was registered at ClinicalTrials.gov. The registration identification number is NCT04788797.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
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 Non-Commercial (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: Julio César Bai, MD, Emeritus Professor of Medicine, Facultad de Medicina, Universidad del Salvador, 640 Rodriguez Peña, Buenos Aires C1051ABB, Argentina. jbai@intramed.net
Received: December 8, 2023
Peer-review started: December 8, 2023
First decision: December 21, 2023
Revised: December 31, 2023
Accepted: February 18, 2024
Article in press: February 18, 2024
Published online: March 21, 2024
ARTICLE HIGHLIGHTS
Research background
The impact of Aspergillus niger proline-specific endoprotease (AN-PEP) on gluten exposure resulting from inadvertent dietary lapses in celiac disease (CeD) patients adhering to a gluten-free diet (GFD) in real-life scenarios remains unknown.
Research motivation
Early-stage research has hinted at AN-PEP’s potential therapeutic role in breaking down gluten before it reaches the intestinal mucosa, potentially serving as an adjunct for managing gluten exposure. Despite AN-PEP’s approval as a dietary supplement, there is a lack of appropriate clinical studies to confirm its efficacy in detoxifying gluten immunogenic peptides (GIP).
Research objectives
To examine the effects of orally administered AN-PEP on inadvertent gluten exposure and symptom prevention in adult CeD patients following their usual GFD in a real-life scenario.
Research methods
This exploratory trial employed a double-blind, randomized, placebo-controlled design involving CeD participants on a long-term GFD. After a 4-wk run-in phase, individuals were randomly assigned to receive either two AN-PEP capsules per meal for 4 wk or a placebo. The study main outcome endpoints were to compare the average weekly stool GIP and the celiac symptom index between run-in and treatment phases and between AN-PEP and placebo arms.
Research results
In this exploratory study, participants showed strong adherence to the GFD. While AN-PEP treatment did not decrease overall stool GIP concentration, the group receiving AN-PEP exhibited a significantly lower prevalence of severe symptoms compared to the placebo group.
Research conclusions
Despite the lack of reduction in stool GIP due to AN-PEP administration in this real-life setting, the significant decrease in the number of symptomatic patients suggests the need for further investigation and more extensive studies.
Research perspectives
Subsequent studies could delve into whether AN-PEP administration showcases a protective effect against gluten exposure using different research models. Additionally, these studies could aim to elucidate the reasons behind the observed reduction in symptomatic patients to better understand the potential mechanisms at play.
