Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2019; 25(22): 2706-2719
Published online Jun 14, 2019. doi: 10.3748/wjg.v25.i22.2706
Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified
Giovanni Bruno, Piera Zaccari, Giulia Rocco, Giulia Scalese, Cristina Panetta, Barbara Porowska, Stefano Pontone, Carola Severi
Giovanni Bruno, Piera Zaccari, Giulia Rocco, Giulia Scalese, Carola Severi, Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Sapienza University of Rome, Rome 00161, Italy
Cristina Panetta, Stefano Pontone, Department of Surgical Sciences, Sapienza University of Rome, Rome 00161, Italy
Barbara Porowska, Department of Cardio-Thoracic, Vascular Surgery and Transplants, Sapienza University of Rome, Rome 00161, Italy
Author contributions: Bruno G, Zaccari P and Rocco G performed the literature search and wrote the manuscript; Porowska B critically revised the manuscript; Scalese G and Panetta C designed and created the figures; Pontone S and Severi C provided scientific guidance and equally contributed to the manuscript as senior authors; all authors revised and approved the final version of this article.
Conflict-of-interest statement: No potential conflicts of interest to report.
Open-Access: This article is an open-access article which was selected byan 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:
Corresponding author: Stefano Pontone, MD, PhD, Research Assistant Professor, Department of Surgical Sciences, Sapienza University of Rome, V.le Regina Elena 324, Rome 00161, Italy.
Telephone: +39-06-49975503
Received: March 12, 2019
Peer-review started: March 13, 2019
First decision: March 27, 2019
Revised: April 2, 2019
Accepted: April 19, 2019
Article in press: April 20, 2019
Published online: June 14, 2019

Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastric parietal cells, are used in the treatment of several acid-related disorders. PPIs are generally well tolerated but, through the long-term reduction of gastric acid secretion, can increase the risk of an imbalance in gut microbiota composition (i.e., dysbiosis). The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Indeed, the resident gut bacteria are needed for multiple vital functions, such as nutrient and drug metabolism, the production of energy, defense against pathogens, the modulation of the immune system and support of the integrity of the gut mucosal barrier. The bacteria are collected in communities that vary in density and composition within each segment of the gastrointestinal (GI) tract. Therefore, every change in the gut ecosystem has been connected to an increased susceptibility or exacerbation of various GI disorders. The aim of this review is to summarize the recently available data on PPI-related microbiota alterations in each segment of the GI tract and to analyze the possible involvement of PPIs in the pathogenesis of several specific GI diseases.

Keywords: Proton pump inhibitors, Hypochloridria, Gut microbiota, Dysbiosis, Gastrointestinal tract, Cancer, Helicobacter pylori, Gastrointestinal infections

Core tip: The gut microbiota plays a fundamental role in the maintenance of human health. However, several drugs, including proton pump inhibitors, can cause dysbiosis, which in turn is responsible for different extra-intestinal and intestinal diseases. An up-to-date review of the literature was conducted to identify changes in gut microbiota composition related to chronic proton pump inhibitor therapy and to highlight the possible pathogenic involvement of dysbiosis in gastrointestinal disorders.