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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Mucosal Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1390025

Proton pump inhibitor alters Th17/Treg balance and induces gut dysbiosis suppressing contact hypersensitivity reaction in mice

Provisionally accepted
Anna Strzępa Anna Strzępa Katarzyna Marcińska Katarzyna Marcińska Aneta Kiecka Aneta Kiecka Monika Majewska-Szczepanik Monika Majewska-Szczepanik Marian Szczepanik Marian Szczepanik *
  • Jagiellonian University Medical College, Kraków, Poland

The final, formatted version of the article will be published soon.

    Proton pump inhibitors (PPIs), such as omeprazole, are the most commonly prescribed drugs. Treatment with PPIs alters gut microbiota composition and reduces the production of reactive oxygen (ROS) and proinflammatory IL-1β, IL-6, and TNF-α cytokines. Here, we show that omeprazole treatment suppresses the development of T cell-dependent inflammatory response using contact hypersensitivity (CHS) response, an animal model of allergic contact dermatitis (ACD), affecting up to 30% of the population. Two-week treatment with omeprazole before CHS induction, reduced inflammatory response in ears measured by ear swelling, ear biopsy weight, MPO activity, and proinflammatory cytokine production. These changes were associated with reduced frequency of TCR+ CD4+ IL-17A+ and TCR+ CD8+ IL-17A+ T cells and increased frequency of TCR+ CD4+ CD25+ FoxP3+ Treg, and TCR+ CD4+ IL-10+ Tr1 cells in peripheral lymphoid organs. Omeprazole treatment decreased the production of ROS, TNF-α, and IL-6, which supported Th17 cell induction, and increased the frequency of Clostridium cluster XIVab and Lactobacillus, implicated in Treg cell induction. The fecal microbiota transplantation (FMT) experiment confirmed the role of omeprazole-induced changes in gut microbiota profile in CHS suppression. Our data suggests that omeprazole ameliorates inflammatory response mediated by T-cells.

    Keywords: Proton Pump Inhibitors, Omeprazole, Contact hypersensitivity, Gut Microbiota, Dysbiosis, immunomodulation ACD -allergic contact dermatitis, ALNC -axillary and inguinal lymph nodes

    Received: 28 Feb 2024; Accepted: 07 Aug 2024.

    Copyright: © 2024 Strzępa, Marcińska, Kiecka, Majewska-Szczepanik and Szczepanik. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Marian Szczepanik, Jagiellonian University Medical College, Kraków, Poland

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.