Opinion Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2019; 25(18): 2149-2161
Published online May 14, 2019. doi: 10.3748/wjg.v25.i18.2149
Alteration of the esophageal microbiota in Barrett's esophagus and esophageal adenocarcinoma
Jing Lv, Lei Guo, Ji-Jun Liu, He-Ping Zhao, Jun Zhang, Ji-Han Wang
Jing Lv, He-Ping Zhao, Ji-Han Wang, Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
Lei Guo, Ji-Jun Liu, Department of Spinal Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
Jun Zhang, Department of Gastroenterology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an 710004, Shaanxi Province, China
Author contributions: Lv J and Guo L searched and reviewed published articles and wrote the manuscript; Liu JJ and Zhao HP conducted online data searches, critically reviewed the article and made revisions to the manuscript; Wang JH and Zhang J made substantial contributions to the conception and design of the study and approved the final version of the article to be published.
Supported by: the National Natural Science Foundation of China, No. 81702067; Shaanxi Natural Science Foundation of China, No. 2018JQ8029; and Shaanxi Natural Science Foundation of China, No. 2017JQ8041.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ji-Han Wang, PhD, Doctor, Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, No.555 You Yi Dong Road, Xi'an 710054, Shaanxi Province, China. 513837742@qq.com
Telephone: +86-029-62818664 Fax: +86-029-87889576
Received: February 12, 2019
Peer-review started: February 14, 2019
First decision: March 20, 2019
Revised: March 27, 2019
Accepted: April 10, 2019
Article in press: April 11, 2019
Published online: May 14, 2019

The incidence of esophageal adenocarcinoma (EAC) has increased in recent decades, and its 5-year survival rate is less than 20%. As a well-established precursor, patients with Barrett's esophagus (BE) have a persistent risk of progression to EAC. Many researchers have already identified some factors that may contribute to the development of BE and EAC, and the identified risks include gastroesophageal reflux (GER), male sex, older age, central obesity, tobacco smoking, Helicobacter pylori (H. pylori) eradication, and the administration of proton pump inhibitors (PPIs) and antibiotics. The human gut harbors trillions of microorganisms, the majority of which are bacteria. These microorganisms benefit the human host in many ways, such as helping in digestion, assisting in the synthesis of certain vitamins, promoting the development of the gastrointestinal immune system, regulating metabolism and preventing invasion by specific pathogens. In contrast, microbial dysbiosis may play important roles in various diseases, such as inflammation and cancers. The composition of the microbiota located in the normal esophagus is relatively conserved without distinct microbial preferences in the upper, middle and lower esophagus. Six major phyla constitute the esophageal microbiota, including Firmicutes, Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and TM7, similar to the oral microbiota. Streptococcus dominates the esophageal microbiota. However, the microbiota varies in different esophageal diseases compared to that in the healthy esophagus. The type I microbiota, which is primarily composed of gram-positive bacteria, is closely associated with the normal esophagus, while type II microbiota has enriched gram-negative bacteria and is mainly associated with the abnormal esophagus. These increased gram-negative anaerobes/microaerophiles include Veillonella, Prevotella, Haemophilus, Neisseria, Granulicatella and Fusobacterium, many of which are associated with BE. The microbial diversity in the esophagus is decreased in EAC patients, and Lactobacillus fermentum is enriched compared to that in controls and BE patients. Furthermore, the microbiota may be associated with BE and EAC by interacting with their risk factors, including central obesity, GER, H. pylori, administration of PPIs and antibiotics. Therefore, a large gap in research must be bridged to elucidate the associations among these factors. Some studies have already proposed several potential mechanisms by which the microbiota participates in human carcinogenesis by complicated interactions with the human host immune system and signaling pathways. The activation of the LPS-TLR4-NF-κB pathway may contribute to inflammation and malignant transformation. This exciting field of gastrointestinal microbiota allows us to unravel the mystery of carcinogenesis from another perspective. Further studies are needed to explore whether the microbiota changes before or after disease onset, to improve our understanding of the pathogenesis, and to find novel targets for prevention, diagnosis and therapy, which could offer more cost-effective and relatively safe choices.

Keywords: Barrett's esophagus, esophageal adenocarcinoma, microorganisms, esophageal microbiota, alteration, dysbiosis

Core tip: Esophageal adenocarcinoma (EAC) is a malignancy with poor prognosis, and Barrett's esophagus (BE) is the only recognized precursor. As part of the human gut, the esophagus harbors distinctive microbiota, and dysbiosis may be related to BE/EAC. Many studies have attempted to characterize the esophageal microbiota in the normal esophagus and in different diseases, but more data are required. Studies on the esophageal microbiota in BE/EAC have mainly concentrated on these associations, and the underlying mechanisms remain blurred. This review focuses on the features and associations of esophageal microbiota and BE/EAC, which might provide some evidence of their relationships.