Clinical Trials Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2019; 25(40): 6129-6144
Published online Oct 28, 2019. doi: 10.3748/wjg.v25.i40.6129
Prebiotic UG1601 mitigates constipation-related events in association with gut microbiota: A randomized placebo-controlled intervention study
Jae Ryang Chu, Saem-Yi Kang, Sung-Eun Kim, Sol-Ji Lee, Young-Chul Lee, Mi-Kyung Sung
Jae Ryang Chu, Saem-Yi Kang, Sung-Eun Kim, Sol-Ji Lee, Mi-Kyung Sung, Department of Food and Nutrition, Sookmyung Women’s University, Seoul 04310, South Korea
Young-Chul Lee, Unigen, Inc., Cheonan 31257, South Korea
Author contributions: Sung MK designed and supervised the research; Chu JR, Kang SY, Kim SE and Lee SJ performed the research; Lee YC provided materials; Chu JR and Kim SE analyzed and interpreted the data; Chu JR prepared the original draft; Kim SE and Sung MK critically revised the manuscript for important intellectual content; Kang SY and Sung MK administered the research; and all authors read and approved the final manuscript.
Supported by the Unigen, Inc.; the Mid-Career Research Program of the National Research Foundation of Korea, No. 2015R1A2A2A01004607; the Basic Science Research Program of the National Research Foundation of Korea, No. NRF-2016R1A6A3A11934151.
Institutional review board statement: This study was performed according to the ethical recommendations of the Declaration of Helsinki and approved by the Institutional Review Board of Sookmyung Women’s University.
Clinical trial registration statement: This study is registered at https://cris.nih.go.kr. The registration identification number is KCT0002422.
Informed consent statement: Written informed consent was obtained from all participants.
Conflict-of-interest statement: Lee YC is an employee of Unigen, Inc. and provided materials for this intervention study. The other authors have no conflicts of interest or financial arrangements that could potentially influence this research. The terms of this arrangement have been reviewed and approved by the Sookmyung Women’s University in accordance with its policy on objectivity in research.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: CONSORT 2010 checklist of information to include when reporting a randomized trial has been completed.
Open-Access: This 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: Mi-Kyung Sung, PhD, Full Professor, Department of Food and Nutrition, Sookmyung Women’s University, 100 Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, South Korea. mksung@sookmyung.ac.kr
Telephone: +82-2-7109395 Fax: +82-2-7109453
Received: July 25, 2019
Peer-review started: July 25, 2019
First decision: August 17, 2019
Revised: September 17, 2019
Accepted: September 27, 2019
Article in press: September 28, 2019
Published online: October 28, 2019
Processing time: 95 Days and 1.5 Hours
Abstract
BACKGROUND

Constipation is a common functional gastrointestinal disorder and its etiology is multifactorial. Growing evidence suggests that intestinal dysbiosis is associated with the development of constipation. Prebiotics are subjected to bacterial fermentation in the gut to produce short-chain fatty acids (SCFAs), which can help relieve constipation symptoms. The prebiotic UG1601 consists of inulin, lactitol, and aloe vera gel, which are known laxatives, but randomized, controlled clinical trials that examine the effects of this supplement on gut microbiota composition are lacking.

AIM

To assess the efficacy of the prebiotic UG1601 in suppressing constipation-related adverse events in subjects with mild constipation.

METHODS

Adults with a stool frequency of less than thrice a week were randomized to receive either prebiotics or a placebo supplement for 4 wk. All participants provided their fecal and blood samples at baseline and at the end of intervention. Gastrointestinal symptoms and stool frequency were evaluated. The concentrations of serum endotoxemia markers and fecal SCFAs were determined. The relative abundance of SCFA-producing bacteria and the gut microbial community in the responders and non-responders in the prebiotics supplementation group were evaluated.

RESULTS

There were no significant differences in gastrointestinal symptoms between groups, although the prebiotic group showed greater symptom improvement. However, after prebiotic usage, serum cluster of differentiation (CD) 14 and lipopolysaccharide (LPS) concentrations were significantly decreased (CD14, P = 0.012; LPS, P < 0.001). The change in LPS concentration was significantly larger in the prebiotic group than in the placebo group (P < 0.001). Fecal SCFAs concentrations did not differ between groups, while the relative abundance of Roseburia hominis, a major butyrate producer, was significantly increased in the prebiotic group (P = 0.045). The abundances of the phylum Firmicutes and the family Lachnospiraceae (phylum Firmicutes, class Clostridia) (P = 0.009) were decreased in the responders within the prebiotic group. In addition, the proportions of the phylum Firmicutes, the class Clostridia, and the order Clostridiales were inversely correlated with several fecal SCFAs (P < 0.05).

CONCLUSION

Alterations in gut microbiota composition, including a decrease in the phylum Firmicutes and an increase in butyrate-producing bacteria, following prebiotic UG1601 supplementation might help alleviate symptom scores and endotoxemia.

Keywords: Prebiotics; Constipation; Gut microbiota; Endotoxemia; Short-chain fatty acids

Core tip: This randomized clinical study assessed the efficacy of the prebiotic UG1601 in suppressing constipation-related adverse events in subjects with mild constipation. Forty adults with a stool frequency of less than thrice a week were received either prebiotics or placebo supplements for 4 wk. Serum endotoxemia markers were decreased and Roseburia hominis, a major butyrate producer was increased after prebiotic usage. The abundance of Firmicutes was deceased in the responders within the prebiotic group representing the inverse associations with several fecal short-chain fatty acids. Thus, alterations in gut microbiota composition following prebiotic UG1601 supplementation might contribute to alleviation of symptom scores and endotoxemia.