Review
Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials

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Summary

To evaluate the evidence for the use of probiotics in the prevention of acute diarrhoea, we did a meta-analysis of the available data from 34 masked, randomised, placebo-controlled trials. Only one trial was community based and carried out in a developing country. Most of the remaining 33 studies were carried out in a developed country in a health-care setting. Evaluating the evidence by types of acute diarrhoea suggests that probiotics significantly reduced antibiotic-associated diarrhoea by 52% (95% CI 35–65%), reduced the risk of travellers' diarrhoea by 8% (−6 to 21%), and that of acute diarrhoea of diverse causes by 34% (8–53%). Probiotics reduced the associated risk of acute diarrhoea among children by 57% (35–71%), and by 26% (7–49%) among adults. The protective effect did not vary significantly among the probiotic strains Saccharomyces boulardii, Lactobacillus rhamnosus GG, Lactobacillus acidophilus, Lactobacillus bulgaricus, and other strains used alone or in combinations of two or more strains. Although there is some suggestion that probiotics may be efficacious in preventing acute diarrhoea, there is a lack of data from community-based trials and from developing countries evaluating the effect on acute diarrhoea unrelated to antibiotic usage. The effect on acute diarrhoea is dependent on the age of the host and genera of strain used.

Introduction

Each year 4 billion diarrhoeal episodes occur worldwide, accounting for 4% of all deaths and 5% of days lost to disability. At an individual level, acute diarrhoea causes impairment in intestinal absorption of both micronutrients and macronutrients, malnutrition, and growth faltering.1, 2 Prevention of acute diarrhoea is an important public-health challenge. A ubiquitous, simple, safe, and cost-effective intervention to prevent acute diarrhoea and its adverse health effects would have considerable public-health implications.

Hand washing is known to reduce the risk of acute diarrhoea. However, attempts to improve hand washing rates are limited by inadequate evidence of its cost-effectiveness, lack of evidence for its effectiveness, and the inevitable complexity of modifying human behaviours.3, 4 Improving sanitary conditions, drinking water, and food preservation and handling methods can also prevent acute diarrheoa. However, it is unlikely that substantial improvement in these areas will be achieved in most developing countries in the near future.5, 6 More recently, vaccines have been proposed as potential candidates to prevent acute diarrhoea, but an effective and affordable vaccine to prevent diarrhoea at the population level is not yet available.7

There is growing evidence that zinc8 and probiotics, either singly or in a combination, can effectively prevent diarrhoea. Probiotics are either monocultures or mixed cultures of live organisms that, applied to animals or human beings, beneficially affect the host by improving the properties of indigenous microflora, hampering the growth of diarrhoeal pathogens, and boosting cellular and humoral immunity.9 Although there is evidence for the therapeutic benefits of probiotics in viral or antibiotic-associated diarrhoea among children,10, 11 evidence for the role of probiotics in preventing acute diarrhoea is not clear. Two previously published meta-analyses included trials mostly carried out in developed countries and provide data on the efficacy of Saccharomyces boulardii and Lactobacillus acidophilus in preventing only antibiotic-associated diarrhoea.12, 13 Two recently published reviews mainly focused on trials done in high-income countries in hospital settings, and were restricted to infants and children only.2, 14

We did a comprehensive analysis of data from all the currently available trials to evaluate the evidence for the efficacy of probiotics in preventing acute diarrhoea, and evaluated the efficacy of probiotics by strain, age groups, causes of acute diarrhoea, and varied formulations.

Section snippets

Search strategy and selection criteria

We searched the PubMed, Medline, Embase, and Cochrane Controlled Trials Registry (CENTRAL) databases using the keywords “probiotic”, “diarrhea”, “acute diarrhea”, “antibiotic associated diarrhea”, “traveler's diarrhea”, “bacterial diarrhea”, “nosocomial diarrhea”, “diarrhea prophylaxis”, “S boulardii”, “L rhamnosus GG”, “L acidophilus”, “L bulgaricus”, “Bifidobacterium”, “Lactobacilli”, and “Sacchromyces” in different combinations. Publications in both English and French published up to

Search results

Our original search yielded 690 publications. 28 of these trials fulfilled the eligibility criteria for inclusion in our analysis (figure 1 and table 1). Webappendix 2 contains a list of the 25 studies that were excluded following detailed evaluation. Five of the included trials27, 34, 37, 46, 50 presented two or more independently analysable results that were distinctly different from each other; hence, we considered them as individual trials. Therefore a total of 34 trials were used for

Discussion

To our knowledge, this is the only comprehensive meta-analysis that examines the preventive role of probiotics by different age groups, setting, cause of acute diarrhoea, probiotic strains, and commonly used probiotic formulation(s). Our results highlight the fact that very few trials have been carried out in the community setting. There has been only one community-based trial to evaluate the efficacy of probiotics in preventing acute diarrhoea among young children in developing countries,

Search strategy and selection criteria

Details of the search strategy and selection criteria can be found in the Methods section.

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