Jong-Myon Bae

doi:10.4178/epih.e2018043

Articles

Page Path: HOME > Epidemiol Health > Volume 40; 2018 > Article

Brief Communication Prophylactic efficacy of probiotics on travelers’ diarrhea: an adaptive meta-analysis of randomized controlled trials: Jong-Myon Bae; Epidemiol Health 2018;40:e2018043.
DOI: https://doi.org/10.4178/epih.e2018043
Published online: August 29, 2018

Department of Preventive Medicine, Jeju National University School of Medicine, Jeju, Korea

Correspondence: Jong-Myon Bae Department of Preventive Medicine, Jeju National University School of Medicine, 102 Jejudaehak-ro, Jeju 63243, Korea E-mail: jmbae@jejunu.ac.kr

• Received: August 1, 2018 • Accepted: August 29, 2018

This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

prev next

16,821 Views
457 Download
20 Web of Science
18 Crossref
27 Scopus

Full Article

Download PDF

Abstract
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
NOTES
SUPPLEMENTARY MATERIALS
REFERENCES

Abstract

OBJECTIVES
The 2017 guideline for the prevention of travelers’ diarrhea (TD) by the International Society of Travel Medicine suggested that ‘there is insufficient evidence to recommend the use of commercially available prebiotics or probiotics to prevent or treat TD.’ However, a meta-analysis published in 2007 reported significant efficacy of probiotics in the prevention of TD (summary relative risk [sRR], 0.85, 95% confidence interval [CI], 0.79 to 0.91). This study aimed to synthesize the efficacy of probiotics on TD by updating the meta-analysis of double-blind, placebo-controlled, randomized human trials.
METHODS
The search process was conducted by the adaptive meta-analysis method using the ‘cited by’ and ‘similar articles’ options provided by PubMed. The inclusion criteria were double-blind, placebo-controlled, randomized human trials with hypotheses of probiotics as intervention and TD as an outcome. The adaptive meta-analysis was conducted using Stata software using the csi, metan, metafunnel, and metabias options.
RESULTS
Eleven articles were selected for the meta-analysis. The sRR was 0.85 (95% CI, 0.79 to 0.91) and showed statistical significance. There was no heterogeneity (I-squared=28.4%) and no publication bias.
CONCLUSIONS
Probiotics showed statistically significant efficacy in the prevention of TD.
Keywords: Probiotics, Diarrhea, Randomized controlled trials, Meta-analysis

INTRODUCTION

While environmental hygiene has improved more than before, travelers’ diarrhea (TD) remains one of the most important public health issues in the international community as more and more people travel around the world [1]. Although it might be possible to consider administering antibiotics to prevent TD, given that bacteria account for more than 80% of the pathogens that cause TD [2], this causes the problem of antibiotic resistance [3]. According to the guideline published in 2017 by the International Society of Travel Medicine (ISTM) [1], antibiotics are contraindicated for the prevention of TD among the general population.

The guideline also states that there is insufficient evidence to recommend the use of commercially available prebiotics or probiotics to prevent or treat TD. Among 2 meta-analysis studies cited in the guideline [4,5], Sazawal et al. [4] selected 4 articles that published randomized, placebo-controlled trial results [6-9], and revealed that there was no significant difference in prevention efficacy (summary relative risk [sRR], 0.92; 95% confidence interval [CI], 0.80 to 1.06). However, McFarland’s study [5], which was published a year later in 2007, added three articles to the four aforementioned articles, selected 7 in total [6-12], and reported that probiotics were effective in preventing TD (sRR, 0.85; 95% CI, 0.79 to 0.91). In addition, a meta-analysis published in 2012 [13] included only 4 articles selected by Sazawal et al. [4] and demonstrated that their systemic review was incomplete.

Accordingly, what needs to be considered first and foremost for this discrepancy regarding the prevention efficacy of probiotics against TD between meta-analysis results and guidelines is that a systematic review should be adapted. The purpose of this study was to reevaluate the prevention efficacy of probiotics against TD using an adaptive meta-analysis.

MATERIALS AND METHODS

Given that this study updated the existing meta-analysis, an adaptive meta-analysis was conducted [14]. This involved creating a list that synthesized articles by ‘cited by’ and ‘similar articles’ provided by PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) for 2 meta-analysis studies [4,5] and their selected seven randomized trial articles [6-12].

The following are exclusion criteria applied to the synthesized list: (1) the subjects were not healthy adults, (2) the study design was not a randomized, placebo-controlled trial, (3) the treatment intervention was not a probiotic, and (4) the outcome was not the efficacy of TD prevention.

Data regarding the total number of subjects and the number of the subjects who developed TD in treatment and control groups were extracted from the finally selected articles. By applying the command csi in the Stata/SE version 14 (StataCorp., College Station, TX, USA), the relative risks (RRs) and 95% CIs were calculated for each article, after which a meta-analysis was conducted by calculating the sRR using the command metan [15]. Heterogeneity among the articles was assessed using the I-squared value (%), and this study applied a fixed effect model when there was no heterogeneity. To identify the existence of publication bias, this study applied the options metafunnel and metabias.

RESULTS

As of July 27, 2018, a list of 1,227 articles was created from the search, and 11 articles were finally selected when the four exclusion criteria were applied (Figure 1) [3,6-10,12,16-19]. Four more articles were selected in addition to the 7 articles chosen in the 2 existing meta-analysis studies. Furthermore, among the 7 articles selected in McFarland’s 2007 study [5], the article published by Kollaritsch et al. [11] was replaced by another article published by Kollaritsch & Wiedermann [19], which contained more detailed information. Table 1 shows the RRs and 95% CIs calculated based on information extracted from 11 articles.

Among the 11 selected articles, only two published since 2006 [16,18] presented intention-to-treat (ITT) and per-protocol (PP) separately. In this regard, when the RRs calculated by PP only were applied, there was efficacy in TD prevention while homogeneity was ensured (I-squared= 28.4%; sRR, 0.85; 95% CI, 0.79 to 0.91) (Figure 2). Statistical significance was ensured even when the value was replaced by ITT (sRR, 0.86; 95% CI, 0.80 to 0.92) (not shown). As a result of funnel plot, Begg’s test, and Egger’s test, it was confirmed that there was no publication bias (Figure 3).

DISCUSSION

While the 2017 ISTM guideline [1] stated that there was insufficient evidence regarding the efficacy of probiotics in the prevention of TD, these results added evidence that probiotics had efficacy in preventing TD. Compared to McFarland’s effect size of 0.85 (95% CI, 0.79 to 0.91) from the seven selected articles [5], that of this study, which added 4 more articles, showed a similar level (sRR, 0.85; 95% CI, 0.79 to 0.91). Given that 2 out of the 4 added articles [3,16] produced the same effect size despite the lack of statistical significance in their RR, it provides evidence for the efficacy of probiotics in preventing TD.

As probiotics are already known to be effective for the management of acute infectious diarrhea and antibiotic-associated diarrhea [20], this meta-analysis in which they also showed prevention efficacy on TD would make it more necessary to conduct a follow-up study in the future. Nonetheless, considering that there were different types of probiotics that also differed in their routes of administration, the observation period varied among the articles, and the results were not classified according to PP and ITT, it would be necessary to ensure more consistency in performing clinical trials.

NOTES

The author has no conflicts of interest to declare for this study.

SUPPLEMENTARY MATERIALS

Supplementary Material: Korean version is available at (http://www.e-epih.org/).

epih-40-e2018043-supplementary.pdf

Figure 1.

Flow chart of articles’ selection.

Figure 2.

Forest plot from 11 selected articles. FA_RN, first author & reference number; ES, effect size.

Figure 3.

Funnel plot (Begg’s test: p=0.94; Egger’s test: p =0.83). SE, standard error; RR, relative risk.

Table 1.

Summaries of 11 selected articles for adaptive meta-analysis

First author [RN]	Publication year	Treatment		Placebo		RR (95% CI)	Probiotics
First author [RN]	Publication year	n	TD	n	TD	RR (95% CI)	Probiotics
de dios Pozo-Olano [6]	1978	26	9	24	7	1.19 (0.52, 2.69)	L. acidophilus & L. bulgaricus
Black [10]	1989	47	20	47	33	0.61 (0.41, 0.89)	Mixed
Kollaritsch [19]	1989	1,148	437	712	321	0.84 (0.76, 0.94)	S. boulardii
Oksanen [7]	1990	373	153	383	178	0.88 (0.75, 1.04)	L. rhamnosus GG
Kollaritsch [12]	1993	655	208	361	141	0.81 (0.69, 0.96)	S. boulardii
Katelaris [8]	1995	181	45	101	24	1.05 (0.68, 1.61)	L. acidophilus & L. fermentum
Hilton [9]	1997	126	5	119	9	0.52 (0.18, 1.52)	L. rhamnosus GG
Briand [16]	2006	79	30	72	22	1.24 (0.79, 1.95)	L. acidophilus
Drakoularakou [17]	2010	81	19	78	30	0.61 (0.38, 0.99)	GO
Virk [3]	2013	94	52	102	55	1.03 (0.79, 1.32)	Mixed
Hasle [18]	2017	167	32	167	48	0.67 (0.45, 0.99)	GO

RN, reference number; TD, travelers’ diarrhea; RR, relative risk; CI, confidence interval; L, Lactobacillus; S, Saccharomyces; GO, galacto-oligosaccharide.

REFERENCES

1. Riddle MS, Connor BA, Beeching NJ, DuPont HL, Hamer DH, Kozarsky P, et al. Guidelines for the prevention and treatment of travelers’ diarrhea: a graded expert panel report. J Travel Med 2017;24:S57-S74.Article PDF
2. Gascón J. Epidemiology, etiology and pathophysiology of traveler’s diarrhea. Digestion 2006;73 Suppl 1:102-108.Article PubMed
3. Virk A, Mandrekar J, Berbari EF, Boyce TG, Fischer PR, Kasten MJ, et al. A randomized, double blind, placebo-controlled trial of an oral synbiotic (AKSB) for prevention of travelers’ diarrhea. J Travel Med 2013;20:88-94.Article PubMed PDF
4. Sazawal S, Hiremath G, Dhingra U, Malik P, Deb S, Black RE. Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infect Dis 2006;6:374-382.Article PubMed
5. McFarland LV. Meta-analysis of probiotics for the prevention of traveler’s diarrhea. Travel Med Infect Dis 2007;5:97-105.Article PubMed
6. de dios Pozo-Olano J, Warram JH Jr, Gómez RG, Cavazos MG. Effect of a lactobacilli preparation on traveler’s diarrhea. A randomized, double blind clinical trial. Gastroenterology 1978;74:829-830.Article PubMed
7. Oksanen PJ, Salminen S, Saxelin M, Hämäläinen P, Ihantola-Vormisto A, Muurasniemi-Isoviita L, et al. Prevention of travellers’ diarrhoea by Lactobacillus GG. Ann Med 1990;22:53-56.Article PubMed
8. Katelaris PH, Salam I, Farthing MJ. Lactobacilli to prevent traveler’s diarrhea? N Engl J Med 1995;333:1360-1361.Article
9. Hilton E, Kolakowski P, Singer C, Smith M. Efficacy of Lactobacillus GG as a diarrheal preventive in travelers. J Travel Med 1997;4:41-43.Article PubMed PDF
10. Black FT, Anderson PL, Orskov J, Orskov F, Gaarslev K, Laulund S. Prophylactic efficacy of Lactobacilli on traveler’s diarrhea. Travel Med 1989;7:333-335.Article
11. Kollaritsch H, Kremsner P, Wiedermann G, Scheiner O. Prevention of traveller’s diarrhea: comparison of different non-antibiotic preparations. Travel Med Int 1989;6:9-17.
12. Kollaritsch H, Holst H, Grobara P, Wiedermann G. Prevention of traveler’s diarrhea with Saccharomyces boulardii. Results of a placebo controlled double-blind study. Fortschr Med 1993;111:152-156 (German).PubMed
13. Ritchie ML, Romanuk TN. A meta-analysis of probiotic efficacy for gastrointestinal diseases. PLoS One 2012;7:e34938.Article PubMed PMC
14. Bae JM, Kim EH. Citation discovery tools for conducting adaptive meta-analyses to update systematic reviews. J Prev Med Public Health 2016;49:129-133.Article PubMed PMC PDF
15. Shim SR, Shin IS, Bae JM. Intervention meta-analysis using STATA software. J Health Info Stat 2016;41:123-134 (Korean).Article PDF
16. Briand V, Buffet P, Genty S, Lacombe K, Godineau N, Salomon J, et al. Absence of efficacy of nonviable Lactobacillus acidophilus for the prevention of traveler’s diarrhea: a randomized, doubleblind, controlled study. Clin Infect Dis 2006;43:1170-1175.Article PubMed PDF
17. Drakoularakou A, Tzortzis G, Rastall RA, Gibson GR. A doubleblind, placebo-controlled, randomized human study assessing the capacity of a novel galacto-oligosaccharide mixture in reducing travellers’ diarrhoea. Eur J Clin Nutr 2010;64:146-152.Article PubMed PDF
18. Hasle G, Raastad R, Bjune G, Jenum PA, Heier L. Can a galactooligosaccharide reduce the risk of traveller’s diarrhoea? A placebo-controlled, randomized, double-blind study. J Travel Med 2017;doi: https://doi.org/10.1093/jtm/tax057.Article
19. Kollaritsch HH, Wiedermann G. Prevention of traveler’s diarrhea: a double-blind randomized trial with Saccharomyces cerevisiae Hansen CBS 5926. Travel Med 1989;7:328-332.Article
20. Wilkins T, Sequoia J. Probiotics for gastrointestinal conditions: a summary of the evidence. Am Fam Physician 2017;96:170-178.PubMed

Figure & Data

References

Citations

Citations to this article as recorded by

The Potential Impact of Probiotics on Human Health: An Update on Their Health-Promoting Properties
Nicoleta-Maricica Maftei, Cosmin Raducu Raileanu, Alexia Anastasia Balta, Lenuta Ambrose, Monica Boev, Denisa Batîr Marin, Elena Lacramioara Lisa
Microorganisms.2024; 12(2): 234. CrossRef
Next generation probiotics: Engineering live biotherapeutics
Sanjeeva Kumar Murali, Thomas J. Mansell
Biotechnology Advances.2024; 72: 108336. CrossRef
Bismuth subsalicylate, probiotics, rifaximin and vaccines for the prevention of travelers’ diarrhea: a systematic review and network meta-analysis
Hao Fan, I-Chun Liu, Lei Gao, Lanka Wu
Frontiers in Pharmacology.2024;[Epub] CrossRef
Haben Probiotikastämme einen nachweisbaren Stellenwert?
Jonas Früh
Flugmedizin · Tropenmedizin · Reisemedizin - FTR.2024; 31(03): 110. CrossRef
Controlling Intestinal Infections and Digestive Disorders Using Probiotics
Sanjeev Kumar, Md Faruque Ahmad, Priyakshi Nath, Rubina Roy, Rudrarup Bhattacharjee, Eman Shama, Indira Gahatraj, Manisha Sehrawat, Vaishali Dasriya, Harmeet Singh Dhillon, Monica Puniya, Mrinal Samtiya, Tejpal Dhewa, Rotimi E. Aluko, Gulab D. Khedkar, An
Journal of Medicinal Food.2023; 26(10): 705. CrossRef
Antibiotic treatment to reduce the duration and severity of travellers’ diarrhoea
Romeo Toriro, William Nevin, Rebecca Kuehn, Hannah Ryan, Nicholas Beeching, Tom Fletcher, Dan Burns
Cochrane Database of Systematic Reviews.2023;[Epub] CrossRef
Phenotypic Assessment of Probiotic and Bacteriocinogenic Efficacy of Indigenous LAB Strains from Human Breast Milk
Senbagam Duraisamy, Fazal Husain, Senthilkumar Balakrishnan, Aswathy Sathyan, Prabhu Subramani, Prahalathan Chidambaram, Selvaraj Arokiyaraj, Wahidah H. Al-Qahtani, Jothiramalingam Rajabathar, Anbarasu Kumarasamy
Current Issues in Molecular Biology.2022; 44(2): 731. CrossRef
Probiotics, their prophylactic and therapeutic applications in human health development: A review of the literature
Bantayehu Addis Tegegne, Bekalu Kebede
Heliyon.2022; 8(6): e09725. CrossRef
Probiotics and rifaximin for the prevention of travelers’ diarrhea: A systematic review and network meta-analysis
Hao Fan, Lei Gao, Zidan Yin, Sheng Ye, Hua Zhao, Qi Peng
Medicine.2022; 101(40): e30921. CrossRef
Gut Microbiota-targeted Interventions for Reducing the Incidence, Duration, and Severity of Respiratory Tract Infections in Healthy Non-elderly Adults
J Philip Karl
Military Medicine.2021; 186(3-4): e310. CrossRef
The effects of probiotics, prebiotics and synbiotics on the reduction of IBD complications, a periodic review during 2009–2020
A. Darb Emamie, M. Rajabpour, R. Ghanavati, P. Asadolahi, S. Farzi, B. Sobouti, A. Darbandi
Journal of Applied Microbiology.2021; 130(6): 1823. CrossRef
Pediatric Digestive Health and the Gut Microbiome: Existing Therapies and a Look to the Future
Samantha Saul, Jessika Fuessel, Joseph Runde
Pediatric Annals.2021;[Epub] CrossRef
A Brief Overview on Probiotics: The Health Friendly Microbes
Sanjukta Mishra, Swastik Acharya
Biomedical and Pharmacology Journal.2021; 14(4): 1869. CrossRef
Therapeutic, Prophylactic, and Functional Use of Probiotics: A Current Perspective
Maria Aponte, Nicoletta Murru, Mahtab Shoukat
Frontiers in Microbiology.2020;[Epub] CrossRef
Probiotics: Reiterating What They Are and What They Are Not
Gregor Reid, Azza A. Gadir, Raja Dhir
Frontiers in Microbiology.2019;[Epub] CrossRef
Probiotics and prebiotics in clinical tests: an update
Harald Brüssow
F1000Research.2019; 8: 1157. CrossRef
A successful history: probiotics and their potential as antimicrobials
Luigi Santacroce, Ioannis Alexandros Charitos, Lucrezia Bottalico
Expert Review of Anti-infective Therapy.2019; 17(8): 635. CrossRef
Emerging concepts in the diagnosis, treatment, and prevention of travelers’ diarrhea
Lorne Schweitzer, Bhagteshwar Singh, Priscilla Rupali, Michael Libman
Current Opinion in Infectious Diseases.2019; 32(5): 468. CrossRef

PubReader
ePub Link
Cite

CITE

export Copy Format

Close

XML Download

Figure

Prophylactic efficacy of probiotics on travelers’ diarrhea: an adaptive meta-analysis of randomized controlled trials

Figure 1. Flow chart of articles’ selection.

Figure 2. Forest plot from 11 selected articles. FA_RN, first author & reference number; ES, effect size.

Figure 3. Funnel plot (Begg’s test: p=0.94; Egger’s test: p =0.83). SE, standard error; RR, relative risk.

Figure 1.

Figure 2.

Figure 3.

Prophylactic efficacy of probiotics on travelers’ diarrhea: an adaptive meta-analysis of randomized controlled trials

First author [RN]	Publication year	Treatment		Placebo		RR (95% CI)	Probiotics
First author [RN]	Publication year	n	TD	n	TD	RR (95% CI)	Probiotics
de dios Pozo-Olano [6]	1978	26	9	24	7	1.19 (0.52, 2.69)	L. acidophilus & L. bulgaricus
Black [10]	1989	47	20	47	33	0.61 (0.41, 0.89)	Mixed
Kollaritsch [19]	1989	1,148	437	712	321	0.84 (0.76, 0.94)	S. boulardii
Oksanen [7]	1990	373	153	383	178	0.88 (0.75, 1.04)	L. rhamnosus GG
Kollaritsch [12]	1993	655	208	361	141	0.81 (0.69, 0.96)	S. boulardii
Katelaris [8]	1995	181	45	101	24	1.05 (0.68, 1.61)	L. acidophilus & L. fermentum
Hilton [9]	1997	126	5	119	9	0.52 (0.18, 1.52)	L. rhamnosus GG
Briand [16]	2006	79	30	72	22	1.24 (0.79, 1.95)	L. acidophilus
Drakoularakou [17]	2010	81	19	78	30	0.61 (0.38, 0.99)	GO
Virk [3]	2013	94	52	102	55	1.03 (0.79, 1.32)	Mixed
Hasle [18]	2017	167	32	167	48	0.67 (0.45, 0.99)	GO

Table 1. Summaries of 11 selected articles for adaptive meta-analysis

RN, reference number; TD, travelers’ diarrhea; RR, relative risk; CI, confidence interval; L, Lactobacillus; S, Saccharomyces; GO, galacto-oligosaccharide.