Clinical Trials Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2019; 25(17): 2110-2121
Published online May 7, 2019. doi: 10.3748/wjg.v25.i17.2110
Beneficial effect of probiotics supplements in reflux esophagitis treated with esomeprazole: A randomized controlled trial
Qing-Hua Sun, Hong-Yan Wang, Shi-Dong Sun, Xin Zhang, Han Zhang
Qing-Hua Sun, Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
Hong-Yan Wang, Shi-Dong Sun, Xin Zhang, Han Zhang, Department of Gastroenterology, PKUCare Luzhong Hospital, Zibo 255400, Shandong Province, China
Author contributions: Sun SD designed the research; Wang HY, Zhang X, and Zhang H performed the research; Sun SD and Wang HY contributed new reagents and analytic tools; Wang HY analyzed the data; Sun QH wrote the paper.
Supported by Shandong Provincial Medical and Health Technology Development Project, No. 2014ws0020.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of PKUCare Luzhong Hospital [2015-KY-003].
Clinical trial registration statement: This study is registered on the Chinese Clinical Trial Registry (No. ChiCTR1800018218).
Informed consent statement: All study participants, or their legal guardian, provided written informed consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data.
CONSORT 2010 statement: CONSORT 2010 checklist of information to include when reporting a randomized trial has been completed.
Open-Access: This article is an open-access article which 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: Shi-Dong Sun, Director, Vice President of Hospital, Department of Gastroenterology, PKUCare Luzhong Hospital, No. 65, Taigong Road, Linzi District, Zibo 255400, Shandong Province, China. sunshidong@163.com
Telephone: +86-533-7698006 Fax: +86-533-7698019
Received: January 11, 2019
Peer-review started: January 11, 2019
First decision: January 30, 2019
Revised: February 15, 2019
Accepted: February 22, 2019
Article in press: February 23, 2019
Published online: May 7, 2019
Processing time: 115 Days and 23.4 Hours
ARTICLE HIGHLIGHTS
Research background

Profound changes have been observed in the gastric and intestinal microbiota of proton pump inhibitor users. Probiotics are commonly administered to patients with intestinal flora abnormalities. No prior studies have been conducted to evaluate the therapeutic effects of probiotics [Bacillus subtilis (B. subtilis) and Enterococcus faecium (E. faecium)] on patients with reflux esophagitis (RE).

Research motivation

We conducted a randomized controlled clinical trial to evaluate the impact of disordered gut microbiota on RE as well as the therapeutic effect of probiotics supplements on patients with RE.

Research objectives

This clinical trial aimed to study the RE patients treated with the combination of probiotic (B. subtilis and E. faecium) and esomeprazole.

Research methods

This study included 134 patients with RE who met the criteria. In phase 1, patients were divided into two groups. The probiotics group was given esomeprazole and live combined B. subtilis and E. faecium enteric-coated capsules for eight weeks, and the placebo group was given esomeprazole and placebo for eight weeks. Endoscopic evaluation, gastrointestinal symptom rating scale (GSRS), reflux diagnostic questionnaire (RDQ), and lactulose hydrogen breath test (LHBT) were performed at the end of the treatment. In phase 2, patients who achieved endoscopic and clinical cure (RDQ < 12) entered the follow-up. RDQ and LHBT were completed at the follow-up endpoint.

Research results

After eight-week treatment, the GSRS diarrhea syndrome score was decreased significantly in the probiotics group, and the small intestinal bacterial overgrowth (SIBO) negative rate in the probiotics group was significantly higher than that in the placebo group. Furthermore, the therapy had a significant influence on relapse time, and the risk of relapse in the probiotics group was lower than that in the placebo group at any time point during the 12-wk follow-up (hazard ratio = 0.52). However, only B. subtilis and E. faecium as probiotics were studied on gut microbiota in our study. More kinds of probiotics should be studied.

Research conclusions

The combined administration of probiotics (B. subtilis and E. faecium) and esomeprazole could reduce the incidence of SIBO and improve abdominal symptoms in patients with RE. It may also prolong the time to relapse, showing the potential of probiotics (B. subtilis and E. faecium) for the treatment and management of RE.

Research perspectives

The limitation of this study is the fact that we did not use jejunal cultures for SIBO assessment and did not perform endoscopy on asymptomatic patients after primary healing was achieved. Additional randomized controlled trials are needed to study more probiotics and different dosages, and prolong the follow-up time to evaluate the long-term effect.