Meta-Analysis
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2019; 25(33): 4999-5016
Published online Sep 7, 2019. doi: 10.3748/wjg.v25.i33.4999
Efficacy of Lactobacillus rhamnosus GG in treatment of acute pediatric diarrhea: A systematic review with meta-analysis
Ya-Ting Li, Hong Xu, Jian-Zhong Ye, Wen-Rui Wu, Ding Shi, Dai-Qiong Fang, Yang Liu, Lan-Juan Li
Ya-Ting Li, Jian-Zhong Ye, Wen-Rui Wu, Ding Shi, Dai-Qiong Fang, Lan-Juan Li, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Ya-Ting Li, Jian-Zhong Ye, Wen-Rui Wu, Ding Shi, Dai-Qiong Fang, Lan-Juan Li, Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Hong Xu, Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou 310003, Zhejiang Province, China
Yang Liu, Department of Orthopedics, Clinical Sciences, Lund, Lund University, Lund 22185, Sweden
Author contributions: Li YT, Xu H, and Ye JZ contributed equally to this work; Li YT and Xu H identified eligible articles and extracted applicable data; Li YT, Xu H, and Ye JZ contributed to the design of the study; Wu WR contributed to the analysis and interpretation of the outcomes; Liu Y, Fang DQ, and Shi D participated in writing and editing the article; all authors approved the final draft of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81330011.
Conflict-of-interest statement: None.
PRISMA 2009 Checklist statement: The guidelines of the PRISMA 2009 Statement have been adopted in this manuscript.
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: Lan-Juan Li, MD, PhD, Academic Research, Doctor, Professor, Senior Researcher, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou 310003, Zhejiang Province, China. ljli@zju.edu.cn
Telephone: +86-571-87236759 Fax: +86-571-87236459
Received: April 28, 2019
Peer-review started: April 28, 2019
First decision: May 30, 2019
Revised: July 4, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: September 7, 2019
Processing time: 132 Days and 15.4 Hours
ARTICLE HIGHLIGHTS
Research background

Diarrhea is a major infectious cause of childhood morbidity and mortality worldwide. Preventing or correcting dehydration through treatment with zinc or 0.9% saline solution is the main approach for diarrhea management; however, during diarrhea episodes, infectious symptoms are not fully alleviated by rehydration measures. Probiotics restore the gut microbiota and have been reported to reduce the duration of diarrhea.

Research motivation

Although previous studies have reported that Lactobacillus rhamnosus GG (LGG) is an effective therapeutic agent for acute diarrhea in children, a recent large, high-quality RCT found no adequate evidence of a beneficial effect of LGG treatment.

Research objectives

To evaluate the efficacy of LGG in treating acute diarrhea in children and provide some reference for future trials of treatments for diarrhea.

Research methods

The EMBASE, MEDLINE, PubMed, Web of Science databases, and the Cochrane Central Register of Controlled Trials were searched up to April 2019 for meta-analyses and randomized controlled trials (RCTs). Cochrane Review Manager was used to analyze the relevant data and primary outcomes, including the duration of diarrhea and diarrhea lasting ≥ 3 and ≥ 4 d. Secondary outcomes included the hospital stay duration, stool frequency, and improvement in stool consistency and vomiting.

Research results

The systematic review identified 19 RCTs that met the inclusion criteria and indicated that compared with the control group, LGG administration notably reduced the diarrhea duration [mean difference (MD) -24.02 h, 95% confidence interval (CI) (-36.58, -11.45)]. Greater reductions were detected at a high dose of ≥ 1010 CFU per day [MD -22.56 h, 95%CI (-36.41, -8.72)] and in LGG participants with diarrhea for less than 3 days at study enrollment [MD -15.83 h, 95%CI (-20.68, -10.98)]. The study locations contributed to differences in the reduction in the diarrhea duration in Asia and Europe [MD -24.42 h, 95%CI (-47.01, -1.82); MD -32.02 h, 95%CI (-49.26, -14.79), respectively]. High-dose LGG treatment was confirmed to effectively reduce the duration of rotavirus-induced diarrhea [MD -31.05 h, 95%CI (-50.31, -11.80)] and stool number [MD -1.08, 95%CI (-1.87, -0.28)].

Research conclusions

The following conclusions were cautiously established: compared to control children, children who received a course of LGG had better outcomes, including a markedly reduced duration of diarrhea, especially those with rotavirus-positive diarrhea, those who received no less than 1010 CFU per day, and those treated at the early stage. Furthermore, studies conducted in Asia and Europe reported greater treatment efficacy. The therapeutic effect of LGG supplementation on the stool number per day and hospital stay duration associated with rotavirus-induced diarrhea was high.

Research perspectives

Our study found better outcomes among children with acute diarrhea who were treated by LGG supplementation. Limited identification of pathogens, small sample sizes, and a lack of a standard clinical parameter format precluded further analyses across studies, thus weakening the evidence required to guide clinical practice. Investigations are required to assess the cost-effectiveness of treating diarrhea with probiotics.