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Cited by 154Probiotics and Fermented FoodsGastrointestinal motility and disordersInfant Nutrition and Health

Probiotics for treating acute infectious diarrhoea

Open access
Collinson, Shelui, Deans, Andrew, Padua-Zamora, April, Gregorio, Germana V, Li, Chao, Dans, Leonila F, Allen, Stephen J·2020·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd003048.pub4PMC PMC8166250
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Abstract

BackgroundProbiotics may be effective in reducing the duration of acute infectious diarrhoea. ObjectivesTo assess the effects of probiotics in proven or presumed acute infectious diarrhoea. Search methodsWe searched the trials register of the Cochrane Infectious Diseases Group, MEDLINE, and Embase from inception to 17 December 2019, as well as the Cochrane Controlled Trials Register (Issue 12, 2019), in the Cochrane Library, and reference lists from studies and reviews.We included additional studies identified during external review. Selection criteriaRandomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent. Data collection and analysisTwo review authors independently applied inclusion criteria, assessed risk of bias, and extracted data.Primary outcomes were measures of diarrhoea duration (diarrhoea lasting ≥ 48 hours; duration of diarrhoea).Secondary outcomes were number of people hospitalized in community studies, duration of hospitalization in inpatient studies, diarrhoea lasting ≥ 14 days, and adverse events. Main resultsWe included 82 studies with a total of 12,127 participants.These studies included 11,526 children (age < 18 years) and 412 adults (three studies recruited 189 adults and children but did not specify numbers in each age group).No cluster-randomized trials were included.Studies varied in the definitions used for "acute diarrhoea" and "end of the diarrhoeal illness" and in the probiotic(s) tested.A total of 53 trials were undertaken in countries where both child and adult mortality was low or very low, and 26 where either child or adult mortality was high.Probiotics for treating acute infectious diarrhoea (Review)

AI snapshot

Written from the paper’s full text.

TL;DR

This Cochrane review of 82 randomized trials found that, in trials at low risk of bias, probiotics probably make little or no difference to whether acute infectious diarrhoea lasts ≥48 hours, and it is uncertain whether they shorten diarrhoea duration. The authors conclude that current evidence does not support using probiotics to treat acute infectious diarrhoea.

Key findings

  • In low-risk-of-bias trials, probiotics vs control showed no difference in diarrhoea lasting ≥48 hours (RR 1.00, 95% CI 0.91 to 1.09; 2 trials, 1770 participants; moderate-certainty evidence).
  • In low-risk-of-bias trials, mean duration of diarrhoea was 8.64 hours shorter with probiotics, but the 95% CI ranged from 29.4 hours shorter to 12.1 hours longer (6 trials, 3058 participants; very low-certainty evidence).
  • Across all trials, pooled estimates suggested benefit (diarrhoea ≥48 hours RR 0.64, 95% CI 0.52 to 0.79; duration MD 21.3 hours shorter, 95% CI 15.7 to 26.9), but heterogeneity was very high and funnel plots suggested publication bias.
  • Duration of hospitalization was shorter in probiotic groups (MD −18.03 hours, 95% CI −27.28 to −8.78; 24 trials, 4056 participants; I² = 96%), but no clear differences were detected for diarrhoea lasting ≥14 days or hospitalization in community studies; no serious adverse events were attributed to probiotics.

Methods

  • Cochrane systematic review and meta-analysis of randomized controlled trials comparing a specified probiotic with placebo or no probiotic in adults and children with acute diarrhoea presumed or proven to be infectious; searches ran to 17 December 2019.
  • Included 82 trials with 12,127 participants (11,526 children and 412 adults; 189 participants of unclear age group), with two reviewers independently assessing eligibility, risk of bias, and extracting data.
  • Primary outcomes were diarrhoea lasting ≥48 hours and duration of diarrhoea; analyses used random-effects models because of marked heterogeneity, with GRADE certainty assessment, prespecified subgroup analyses, and sensitivity analyses limited to trials at low risk of bias.

Limitations

  • The paper states that many included studies had high or unclear risk of bias, statistical heterogeneity was marked and largely unexplained, and funnel plots indicated publication bias.
  • The paper notes that most participants were children, adult data were sparse, definitions of acute diarrhoea and recovery varied widely, and probiotic identity/viability was confirmed in only a few trials; adverse-event reporting was limited.
  • The most robust analysis was restricted to only 2 trials for diarrhoea lasting ≥48 hours and 6 trials for duration, and GRADE certainty was moderate for the former and very low for the latter.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1002/14651858.cd003048.pub4

Cites

202 of 203 references verified0 citation errors · 1 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

26 of 44 cited sources checked · 19 supported · 2 flagged · accuracy not yet measured

  • Interpretationcitation

    The very marked heterogeneity between studies in this and other reviews argues against 'core' properties shared by different probiotics that are effective against diarrhoea due to many different infectious agents and its occurrence in different populations and regions.

    “The very marked heterogeneity between studies in this and other reviews argues against “core” properties shared by different probiotics that are effective against diarrhoea due to many different infectious agents and its occurrence in different populations and regions (Hill 2014).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Hill 2014 source

      The Core benefits section (p. 3) takes the opposite position: the panel says evidence supports ‘core’ benefits of certain probiotics and explicitly contrasts that view with the idea that every strain produces a different outcome. The Consensus statements (p. 3) also include infectious diarrhoea among the outcomes considered in support of general digestive-tract benefits. The paper does not use study heterogeneity to argue against shared properties. (LLM, conf=0.89)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Interpretationreasoning

    Our findings do not support recommendations for the use of specific probiotics for acute infectious diarrhoea in children.

    “Our findings do not support recommendations for the use of specific probiotics for acute infectious diarrhoea in children (Floch 2015; Guarino 2018; Sniffen 2018).”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites Floch 2015 source
    • cites Guarino 2018 source
    • cites Sniffen 2018 source

      The Discussion (page unavailable) says the opposite: it finds strong evidence of efficacy for several specific probiotics in treating pediatric acute diarrhea, and moderate evidence for another formulation. The Results section also reports that S. boulardii reduced diarrhea duration in children. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    In children from middle- and high-income countries, probiotics reduced stool frequency on day two by 13.1% (95% CI 0.8% to 25.3%).

    “In children from middle‐ and high‐income countries, probiotics reduced diarrhoea duration by 14% (95% CI 3.8% to 24.2%) and stool frequency on day two by 13.1% (95% CI 0.8% to 25.3%; Applegate 2013).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Applegate 2013 source
  • Premisecitation

    Due to substantive heterogeneity of effect size between studies, evidence was insufficient to show a specific probiotic regimen as more effective than another.

    “However, due to substantive heterogeneity of effect size between studies, evidence was insufficient to show a specific probiotic regimen as more effective than another (Allen 2010).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Allen 2010 source
  • Premisecitation

    In children from middle- and high-income countries, probiotics reduced diarrhoea duration by 14% (95% CI 3.8% to 24.2%).

    “In children from middle‐ and high‐income countries, probiotics reduced diarrhoea duration by 14% (95% CI 3.8% to 24.2%) and stool frequency on day two by 13.1% (95% CI 0.8% to 25.3%; Applegate 2013).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Applegate 2013 source
  • May combine two claims. 65
  • Classified as probably not a substantial claim. 19
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingcitation

    Two recently conducted large trials in children did not show a probiotic effect for the number of children with diarrhoea lasting ≥ 48 hours or for mean duration of diarrhoea.

    “A notable finding was that two recently conducted large trials undertaken in children did not show a probiotic effect for the number of children with diarrhoea lasting ≥ 48 hours (Analysis 1.1) or for mean duration of diarrhoea (Analysis 1.2; Freedman 2018a; Schnadower 2018).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Freedman 2018a

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Schnadower 2018 source

      The Results > Secondary Outcomes section reports no significant difference in diarrhea duration between the probiotic and placebo groups. The Abstract > Results gives median durations, not mean durations. Our copy does not report a comparison of the number of children whose diarrhea lasted at least 48 hours; its 48-hour subgroup concerns symptoms before treatment. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Two recent studies each recruited a large number of participants, potentially making a significant contribution to the evidence base.

    “Finally, two recent studies each recruited a large number of participants, potentially making a significant contribution to the evidence base (Freedman 2018a; Schnadower 2018).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Freedman 2018a

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Schnadower 2018 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Two review authors independently assessed risk of bias for each trial using the Cochrane Risk of bias assessment tool.

    “Two review authors independently assessed the risk of bias for each trial using the Cochrane ’Risk of bias’ assessment tool (Higgins 2012).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Higgins 2012 source

      The Introduction (page unavailable) identifies this paper’s subject as inconsistency in network meta-analysis, not the Cochrane Risk of Bias tool. Searches for the tool and for independent trial-level risk-of-bias assessment found no passage in our copy that identifies the tool or describes the cited assessment procedure. (LLM, conf=0.77)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    Schnadower 2018 reported similar rates of adverse events in the two groups, except wheezing was more common in children receiving L rhamnosus GG than controls (5/472 versus 0/479; P = 0.03), and serious adverse events occurred in a similar number in each group.

    “Schnadower 2018 reported similar rates of adverse events in the two groups, except that wheezing was more common in children receiving L rhamnosus GG than in controls (5/472 versus 0/479 children; P = 0.03; borderline statistical significance in view of multiple comparisons); SAEs occurred in a similar number of children in each group.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Schnadower 2018 source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    The identity and viability of probiotic organisms were evaluated by bacteriology and molecular methods in seven studies, and independently of the study team in two of these.

    “The identity and viability of probiotic organisms were evaluated by bacteriology and molecular methods in seven studies (Freedman 2015; Freedman 2018a; Hong Chau 2018; Mao 2008; Rosenfeldt 2002a; Rosenfeldt 2002b; Schnadower 2018), and were evaluated independently of the study team in two of these studies (Freedman 2015; Schnadower 2018).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Freedman 2015 source
    • cites Freedman 2018a

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Schnadower 2018 source

      The Methods section (“Testing of Stool Samples and L. rhamnosus GG Testing”; page not provided) says the trial’s probiotic capsules were independently tested for contaminants and viability. The Results section reports colony-forming-unit measurements. Our copy does not say that molecular methods were used to verify the probiotic’s identity; its PCR testing concerned stool pathogens. This paper also does not establish the citing sentence’s totals of seven studies and two independently evaluated studies. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The Lactobacillus casei group comprises closely related species L casei, L paracasei, and L rhamnosus, including L rhamnosus GG, and these species are difficult to differentiate.

    “The Lactobacillus casei group comprises the closely related species L casei, L paracasei, and L rhamnosus, including L rhamnosus GG, and it is difficult to differentiate between these species (Hill 2018).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Hill 2018 source

  • May combine two claims.

    Findingcitation

    Fifty studies reported that no adverse events were attributed to the probiotic(s), and two studies stated that no serious adverse events were attributed to the probiotic.

    “Fifty studies reported that no adverse events (AEs) were attributed to the probiotic(s), and two studies stated that no serious AEs (SAEs) were attributed to the probiotic (Phavichitr 2013; Simadibrata 2013).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Phavichitr 2013

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Simadibrata 2013 source

  • May combine two claims.

    Premisecitation

    A systematic review of L reuteri DSM 17938 for treating acute gastroenteritis in children reported marked statistical heterogeneity and very low certainty of evidence for both duration of diarrhoea and duration of hospitalization.

    “A systematic review of L reuteri DSM 17938 for treating acute gastroenteritis in children reported marked statistical heterogeneity and very low certainty of evidence for both duration of diarrhoea and duration of hospitalization (Patro‐Gołab 2019).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Patro‐Gołab 2019 source

  • May combine two claims.

    Premisecitation

    A recent systematic review and network meta-analysis of interventions for acute diarrhoea in children reported high statistical heterogeneity for duration of diarrhoea for L rhamnosus GG, S boulardii, and other probiotics grouped together versus standard treatment, and certainty of evidence was graded as low or very low.

    “A recent systematic review and network meta‐analysis of interventions for acute diarrhoea in children reported high statistical heterogeneity for duration of diarrhoea for L rhamnosus GG, S boulardii, and other probiotics grouped together versus standard treatment and certainty of evidence was graded as low or very low (Florez 2018).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Florez 2018 source

  • May combine two claims.

    Premisecitation

    A recent systematic review that summarised trials of S boulardii in children with rotavirus diarrhoea (n = 548 children; five RCTs) reported a modest reduction in diarrhoea duration (MD -0.57 days; 95% CI -0.83 to -0.30) with consistency in findings (I2 = 0%) and moderate certainty evidence.

    “A recent systematic review that summarised trials of S boulardii in children with rotavirus diarrhoea (n = 548 children; five RCTs) reported a modest reduction in diarrhoea duration (MD –0.57 days; 95% CI –0.83 to –0.30) with consistency in findings (I2 = 0%) and moderate certainty evidence (Padayachee 2019).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Padayachee 2019 source

      Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    The review included 82 randomized controlled trials with a total of 12,127 participants.

    “We included 82 studies with a total of 12,127 participants.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Heterogeneity was not explained by types of participants (age, nutritional/socioeconomic status captured by mortality stratum, region of the world where studies were undertaken), diarrhoea in children caused by rotavirus, exposure to antibiotics, and the few studies of children who were also treated with zinc.

    “Heterogeneity also was not explained by types of participants (age, nutritional/socioeconomic status captured by mortality stratum, region of the world where studies were undertaken), diarrhoea in children caused by rotavirus, exposure to antibiotics, and the few studies of children who were also treated with zinc.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Pre-specified subgroup analyses included analyses limited to the probiotics Lactobacillus rhamnosus GG and Saccharomyces boulardii.

    “These included analyses limited to the probiotics Lactobacillus rhamnosus GG and Saccharomyces boulardii.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Of the included trials, 53 were undertaken in countries where both child and adult mortality was low or very low, and 26 where either child or adult mortality was high.

    “A total of 53 trials were undertaken in countries where both child and adult mortality was low or very low, and 26 where either child or adult mortality was high.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Effect size was similar and marked heterogeneity persisted in pre-specified subgroup analyses of the primary outcomes that included all studies.

    “Effect size was similar and marked heterogeneity persisted in pre‐specified subgroup analyses of the primary outcomes that included all studies.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    No cluster-randomized trials were included.

    “No cluster‐randomized trials were included.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no clear differences in effect size for the primary outcomes in post hoc analyses according to decade of publication of studies and whether or not trials had been registered.

    “In addition, there were no clear differences in effect size for the primary outcomes in post hoc analyses according to decade of publication of studies and whether or not trials had been registered.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    The included studies varied in the definitions used for 'acute diarrhoea' and 'end of the diarrhoeal illness' and in the probiotic(s) tested.

    “Studies varied in the definitions used for “acute diarrhoea” and “end of the diarrhoeal illness” and in the probiotic(s) tested.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Of the included studies, 41 (50.0%) were low risk for generation of allocation sequence, 12 (14.6%) for concealment of allocation, 36 (43.9%) for blinding of participants and personnel, 30 (36.6%) for blinding of outcome assessment, 65 (79.3%) for loss to follow-up, and 71 (86.6%) for selective reporting.

    “Forty‐one (50.0%) studies were considered low risk for generation of the allocation sequence, 12 (14.6%) for concealment of allocation, 36 (43.9%) for blinding of participants and personnel, 30 (36.6%) for blinding of outcome assessment, 65 (79.3%) for loss to follow‐up, and 71 (86.6%) for selective reporting (Figure).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The review included 82 studies with a total of 12,127 participants.

    “In total, 82 studies met the inclusion criteria (Characteristics of included studies).”
    • Also stated in: § Summary of main results · plain
      “This review included 82 studies with a total of 12,127 participants.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The included studies comprised 11,526 children (age < 18 years) and 412 adults, with three studies recruiting 189 adults and children but not specifying numbers in each age group.

    “These studies included 11,526 children (age < 18 years) and 412 adults (three studies recruited 189 adults and children but did not specify numbers in each age group).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The 82 selected studies recruited 11,526 children (age < 18 years) and 412 adults.

    “The 82 selected studies recruited a total of 12,127 participants, including 11,526 children (age < 18 years) and 412 adults.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In six trials (433 participants) of Lactobacillus reuteri, there was consistency amongst findings (I2 = 0%).

    “In six trials (433 participants) of Lactobacillus reuteri, there was consistency amongst findings (I² = 0%)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Effect size was similar in the sensitivity analysis and marked heterogeneity persisted.

    “Effect size was similar in the sensitivity analysis and marked heterogeneity persisted.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In seven trials (2333 participants) of acute diarrhoea in the community, probiotics did not reduce the risk of hospitalization (RR 1.21, 95% CI 0.86 to 1.69) with consistency between studies (I2 = 0%).

    “In seven trials (2333 participants) of acute diarrhoea in the community, probiotics did not reduce the risk of hospitalization (RR 1.21, 95% CI 0.86 to 1.69) with consistency in findings between studies (I² = 0%; Analysis 2.1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The effect estimate for probiotics on duration of diarrhoea in children treated with zinc was similar to the main analysis, and marked heterogeneity persisted.

    “The effect estimate for probiotics on the duration of diarrhoea in children treated with zinc was similar to that in the main analysis, and marked statistical heterogeneity persisted (Analysis 10.1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For both diarrhoea lasting ≥ 48 hours and mean duration of diarrhoea, effect estimates were similar in studies where participants may have been exposed to antibiotics before recruitment and marked heterogeneity persisted.

    “For both diarrhoea lasting ≥ 48 hours and mean duration of diarrhoea, effect estimates were similar in studies where participants may have been exposed to antibiotics before recruitment and marked statistical heterogeneity between studies persisted (Analysis 9.1; Analysis 9.2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no clear differences in effect sizes when primary outcomes were analysed according to decade of publication or trial registration, and heterogeneity persisted.

    “However, there were no clear differences in effect sizes in these analyses, and heterogeneity persisted.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    When analysis was restricted to studies where all indicators of risk of bias were low, there was no heterogeneity and consistent estimates of null effect in the two large studies for number of participants with diarrhoea lasting ≥ 48 hours (RR 1.00, 95% CI 0.91 to 1.09; I2 = 0%; two trials, 1770 participants).

    “When analysis was restricted to studies where all indicators of risk of bias were low, there was no heterogeneity with consistent estimates of null effect in the two large studies meeting these criteria for number of participants with diarrhoea lasting ≥ 48 hours between study arms (RR 1.00, 95% CI 0.91 to 1.09; I² = 0%; two trials, 1770 participants; Analysis 11.1: subgroup 7).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For trials reporting mean duration of diarrhoea that were at low risk of bias for all six indices, no difference was demonstrated between intervention and control (MD 8.6 hours less, 95% CI 29.4 less to 12.1 hours more; 6 trials, 3058 participants), with heterogeneity persisting (I2 = 97%).

    “Similarly, for trials reporting mean duration of diarrhoea that were at low risk of bias for all six indices of study quality, no difference was demonstrated between intervention and control (MD 8.6 hours less, 95% CI 29.4 less to 12.1 hours more; 6 trials, 3058 participants). Heterogeneity persisted (I² = 97%; Analysis 11.2: subgroup 7).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In nine trials (2928 participants), probiotics did not reduce the risk of diarrhoea lasting ≥ 14 days (RR 0.49, 95% CI 0.16 to 1.53) with heterogeneity between studies (I2 = 60%).

    “In nine trials (2928 participants), probiotics did not reduce the risk of diarrhoea lasting ≥ 14 days (RR 0.49, 95% CI 0.16 to 1.53) with heterogeneity in findings between studies (I² = 60%; Analysis 2.3).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The remaining 17 studies did not report on adverse events.

    “The remaining 17 studies did not report on adverse events.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For rotavirus diarrhoea, the effects of probiotics were similar to those in the main analyses, but with marked statistical heterogeneity and risk of bias in many studies.

    “For this diarrhoeal pathogen, the effects of probiotics were similar to those in the main analyses, but again with marked statistical heterogeneity and risk of bias in many studies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Although most studies reported absence of adverse events due to probiotics, few studies provided a description of the methods used for detecting and classifying adverse events and few reported specific data on adverse events.

    “Although most studies reported absence of adverse events due to probiotics, few studies provided a description of the methods used for detecting and classifying adverse events and few reported specific data on adverse events.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Effect sizes were similar and heterogeneity persisted in pre-planned subgroup analyses according to probiotic strain, rotavirus diarrhoea, age, severity of illness, country mortality stratum or region, exposure to antibiotics, treatment with zinc in children, and risk of bias.

    “Effect sizes were similar and heterogeneity persisted in our pre‐planned subgroup analyses according to probiotic strain, diarrhoea caused by rotavirus, age, severity of illness, country mortality stratum or region, exposure to antibiotics, treatment with zinc in children, and risk of bias.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was great variability in the methodological quality of trials, but this did not appear to have contributed to heterogeneity.

    “There was great variability in the methodological quality of trials, but this did not appear to have contributed to heterogeneity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Funnel plots were suggestive of publication bias for diarrhoea lasting ≥ 48 hours (Harbord test t = -4.57, P < 0.001) and possibly also for mean duration of diarrhoea (Egger's test t = -3.33, P = 0.002).

    “The funnel plots are suggestive of publication bias for diarrhoea lasting ≥ 48 hours (Figure; Habord test; t = ‐4.57, P < 0.001) and possibly also mean duration of diarrhoea (Figure; Egger’s test; t = ‐3.33, P = 0.002).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Most study participants were children, and available data for adults are sparse.

    “However, most study participants were children, and available data for adults are sparse.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Heterogeneity was not resolved in sensitivity analysis according to individual parameters of risk of bias nor in subgroup analysis of trials where risk of bias for all six parameters was low.

    “Heterogeneity was not resolved in sensitivity analysis according to individual parameters of risk of bias nor in subgroup analysis of trials where risk of bias for all six parameters was low.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For children younger than five years, the effect estimate for diarrhoea lasting ≥ 48 hours was lower than in the main analysis (26 studies, 5033 children; RR 0.72, 95% CI 0.59 to 0.88) and marked heterogeneity persisted (I2 = 97%).

    “For children younger than five years, the effect estimate for diarrhoea lasting ≥ 48 hours was lower than in the main analysis (26 studies, 5033 children; RR 0.72, 95% CI 0.59 to 0.88) and marked statistical heterogeneity persisted (I² = 97%; Analysis 5.1: subgroup 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Great variability in reported outcomes is evident, which limited data available for meta-analysis for the primary outcomes.

    “Also great variability in reported outcomes is evident, which limited data available for meta‐analysis for the primary outcomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Fifteen studies were registered in a trial database; for both primary outcomes, effect estimates were similar to the main analysis in these studies and marked heterogeneity persisted.

    “Fifteen studies were registered in a trial database. For both primary outcomes, effect estimates were similar to the main analysis in these studies, and marked statistical heterogeneity persisted (Analysis 13.1; Analysis 13.2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Diarrhoea lasting ≥ 48 hours was reported in 21 studies (2354 participants) of participants who required admission; the effect estimate (RR 0.62, 95% CI 0.52 to 0.74) was similar to all studies and marked heterogeneity persisted (I2 = 75%).

    “Diarrhoea lasting ≥ 48 hours was reported in 21 studies (2354 participants) of participants who required admission and therefore were likely to have more severe illness. The effect estimate in these trials (RR 0.62, 95% CI 0.52 to 0.74) was similar to all studies, and marked heterogeneity in findings persisted (I² = 75%; Analysis 6.1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In fewer studies, the effect estimate for L reuteri in reducing duration of diarrhoea was similar to the main analysis but with less heterogeneity (6 studies/433 participants; MD 22.8 hours, 95% CI 13.7 to 32.0; I2 = 48%).

    “In fewer studies, the effect estimate for L reuteri in reducing the duration of diarrhoea was similar to that in the main analysis but with less heterogeneity across studies (6 studies/433 participants; MD 22.8 hours, 95% CI 13.7 to 32.0; I² = 48%; Analysis 3.2: subgroup 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In 20 studies (1414 participants, all children), the reduction in duration of diarrhoea was similar to the main analysis and marked heterogeneity persisted (MD 22.1 hours, 95% CI 14.2 to 29.9; I2 = 84%).

    “In 20 studies (1414 participants, all of whom were children), the reduction in duration of diarrhoea was similar to that in the main analysis, and marked statistical heterogeneity between studies persisted (MD 22.1 hours, 95% CI 14.2 to 29.9; I² = 84%; Analysis 4.1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Pooled estimates of probiotic effect for Lactobacillus rhamnosus GG, Saccharomyces boulardii, and Lactobacillus reuteri were similar to the overall findings, and statistical heterogeneity persisted for L rhamnosus GG and S boulardii.

    “Pooled estimates of probiotic effect for these strains were similar to our overall findings, and statistical heterogeneity persisted for the first two strains.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among participants taking S boulardii, the effect estimate for diarrhoea lasting ≥ 48 hours was similar to the main analysis but not statistically significant and with marked heterogeneity (RR 0.70, 95% CI 0.37 to 1.33; 9 studies, 1823 participants; I2 = 99%).

    “The effect estimate for diarrhoea lasting ≥ 48 hours among participants taking S boulardii was similar to the main analysis but was not statistically significant and findings show marked heterogeneity (RR 0.70, 95% CI 0.37 to 1.33; 9 studies, 1823 participants; I² = 99%; Analysis 3.1: subgroup 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Trials that evaluated L reuteri had less heterogeneity but risk of bias was present in all included studies.

    “Trials that evaluated L reuteri had less heterogeneity but risk of bias was present in all included studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among trials of adults, there was greater consistency (I2 = 0%), but only a few trials were included and risk of bias was present in many.

    “Although there was greater consistency among trials of adults (I² = 0%), only a few of these trials were included in this analysis and risk of bias was present in many.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Mean duration of diarrhoea was reported in 36 inpatient studies (5071 participants) and 8 outpatient studies (828 participants); effect estimates were similar and marked heterogeneity was present in both (I2 = 97% and 94%).

    “Mean duration of diarrhoea was reported in 36 inpatient studies (5071 participants) and in 8 outpatient studies (828 participants). The effect estimate was similar in these two groups, and marked heterogeneity was present in both analyses (I² = 97% and 94%, respectively; Analysis 6.2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among participants taking S boulardii, the reduction in duration of diarrhoea was similar to the main analysis and marked heterogeneity persisted (MD 24.6 hours, 95% CI 14.0 to 35.3; 11 studies, 1617 participants; I2 = 89%).

    “The reduction in duration of diarrhoea was similar to that in the main analysis, and marked statistical heterogeneity persisted (MD 24.6 hours, 95% CI 14.0 to 35.3; 11 studies, 1617 participants; I² = 89%; Analysis 3.2: subgroup 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In 24 inpatient trials (4056 participants), duration of hospitalization was reduced in the probiotic arm (MD 18.0 hours, 95% CI 8.8 to 27.3) with marked statistical heterogeneity (I2 = 95%).

    “In 24 inpatient trials (4056 participants), duration of hospitalization was reduced in the probiotic arm (MD 18.0 hours, 95% CI 8.8 to 27.3) but with marked statistical heterogeneity (I² = 95%; Analysis 2.2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Effect estimates were similar when studies were grouped according to geographical region, and statistical heterogeneity persisted except in studies done in the Eur-A region (I2 = 27%).

    “Effect estimates were also similar when studies were grouped according to geographical region. Statistical heterogeneity persisted in these analyses with the exception of studies done in the Eur‐A region (Analysis 8.1: subgroup 3; I² = 27%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among all trials included in this review, there was evidence of publication bias in trials reporting numbers of participants with diarrhoea lasting 48 hours or longer, with a greater number of smaller studies reporting a positive effect of probiotics.

    “Among all trials included in this review, there was evidence of publication bias in trials reporting numbers of participants with diarrhoea lasting 48 hours or longer, with a greater number of smaller studies reporting a positive effect of probiotics (Figure).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The effect estimate for diarrhoea lasting ≥ 48 hours was similar according to decade of publication, with a borderline statistically significant difference in the most recent studies (from 2010; 15 trials/3972 participants; RR 0.78, 95% CI 0.63 to 0.98).

    “The effect estimate for diarrhoea lasting ≥ 48 hours was similar according to decade of publication (Analysis 12.1), and the difference between groups was of borderline statistical significance in the most recent studies (from 2010; 15 trials/3972 participants; RR 0.78, 95% CI 0.63 to 0.98; Analysis 12.1; subgroup 4).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Diarrhoea aetiology was determined in only a minority of studies, and meta-analysis was possible only for rotavirus diarrhoea.

    “In keeping with clinical management, diarrhoea aetiology was determined in only a minority of studies and meta‐analysis was possible only for rotavirus diarrhoea.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In adults (≥ 18 years; 5 studies, 393 participants), probiotics reduced the RR of diarrhoea lasting ≥ 48 hours to a lesser degree than in the main analysis but with consistency between studies (RR 0.62, 95% CI 0.54 to 0.71; I2 = 0%).

    “in fewer studies of adults (≥ 18 years; 5 studies, 393 participants), probiotics reduced the RR of diarrhoea lasting ≥ 48 hours to a lesser degree than in the main analysis but with consistency between studies (RR 0.62, 95% CI 0.54 to 0.71; I² = 0%; Analysis 5.1: subgroup 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Analysis limited to trials at low risk of bias changed our conclusion because these trials do not provide evidence of probiotic efficacy.

    “Analysis of these trials has changed our conclusion as they do not provide evidence of probiotic efficacy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Heterogeneity persisted in analyses by WHO world region and country mortality stratum, except in studies done in the Eur-A region.

    “Heterogeneity persisted in these analyses with the exception of studies done in the Eur‐A region”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Marked statistical heterogeneity and presence of risk of bias were evident in studies that included people exposed to antibiotics and in the few studies of children treated with zinc.

    “Marked statistical heterogeneity and presence of risk of bias were also evident in studies that included people exposed to antibiotics and in the few studies of children treated with zinc.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In analysis limited to trials evaluating the same probiotic strain, there was marked heterogeneity in findings and risk of bias in many of the included trials.

    “In analysis limited to trials evaluating the same probiotic strain, there was marked heterogeneity in findings and risk of bias in many of the included trials.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Two review authors independently reviewed titles and abstracts to identify potentially relevant studies.

    “Two review authors independently reviewed the titles of articles and, when available, abstracts generated by the search to identify potentially relevant studies.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    We did not include quasi-randomized and unpublished studies to keep results as robust as possible.

    “To maximize the use of available data, we included participants of all ages and non‐blinded (open) studies; however, to keep results as robust as possible, we did not include quasi‐randomized and unpublished studies.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Eligibility was assessed independently by two review authors using a standard form.

    “Eligibility was assessed independently by these two people using a standard form and based on the information presented in the article.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Two review authors independently extracted data using standard forms and compared the results.

    “Two review authors independently extracted data using standard forms and compared the results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Two review authors independently applied inclusion criteria, assessed risk of bias, and extracted data.

    “Two review authors independently applied inclusion criteria, assessed risk of bias, and extracted data.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given

    This analysis is based on large trials with low risk of bias.

    “This analysis is based on large trials with low risk of bias.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Trial reports were scrutinized to ensure that multiple publications from the same trial were included only once.

    “Trial reports were scrutinized to ensure that multiple publications from the same trial were included only once.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    We attempted to identify all relevant studies regardless of language.

    “We attempted to identify all relevant studies regardless of language.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Between-study heterogeneity may be due to other differences between trials such as the definitions used for acute diarrhoea and the end of the diarrhoeal episode.

    “Between‐study heterogeneity may be due to other differences between trials such as the definitions used for “acute diarrhoea” and “the end of the diarrhoeal episode.””
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Differences in causes of diarrhoea likely account for some of the statistical heterogeneity between studies and have likely changed over time.

    “Differences in causes of diarrhoea likely account for some of the statistical heterogeneity between studies and have likely changed over time, for example, as a result of immunization programmes such as those for rotavirus.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Probiotics were not associated with adverse events, but reporting was limited.

    “Probiotics were not associated with adverse events, but reporting was limited.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The included trials were undertaken in many different countries from different world regions and were adequate to address the main research question.

    “The included trials were undertaken in many different countries from different world regions and, therefore, were adequate to address the main research question.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A recent review found no evidence that the source of funding for trials of probiotics in diarrhoea had affected trial results.

    “However, a recent review found no evidence that the source of funding for trials of probiotics in diarrhoea had affected trial results (Saa 2019).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Saa 2019 source

  • May combine two claims.

    Interpretationown data

    Probiotics did not prevent hospitalization with acute diarrhoea, with consistency in study findings.

    “Probiotics did not prevent hospitalization with acute diarrhoea, with consistency in study findings.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Marked statistical heterogeneity in the duration of diarrhoea was reported in another recent review of L rhamnosus GG in paediatric diarrhoea.

    “Similarly, marked statistical heterogeneity in the duration of diarrhoea was reported in another recent review of L rhamnosus GG in paediatric diarrhoea (Li 2019).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Li 2019

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Correspondence following this review highlighted that the effect of the probiotic was not statistically significant when analysis was limited to studies at low risk of bias, and that marked heterogeneity persisted in these analyses.

    “Correspondence following this review highlighted that the effect of the probiotic was not statistically significant when analysis was limited to studies at low risk of bias (Schnadower 2019b), and that marked heterogeneity persisted in these analyses (Szajewska 2019b).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Schnadower 2019b

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Szajewska 2019b

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Marked variability in study design likely contributed to the high level of statistical heterogeneity.

    “Marked variability in study design likely contributed to the high level of statistical heterogeneity.”
    Quote in the paperNot a substantial claim
78 of 78

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting heterogeneity estimates for L reuteri trials

    Major

    The abstract reports I2 = 0% for six L reuteri trials with 433 participants, but the results report I2 = 48% for six trials with the same participant count.

  • Conflicting results for hospitalization in community studies

    Major

    The abstract gives six studies, 2283 participants, and RR 1.26, while the results give seven trials, 2333 participants, and RR 1.21 for the same outcome. The text does not identify these as different analyses.

  • Conflicting heterogeneity estimates for hospitalization duration

    Minor

    For the same 24 inpatient trials and 4056 participants, the abstract reports I2 = 96%, whereas the results report I2 = 95%.

  • Adult risk ratio is described as a smaller reduction

    Minor

    The adult subgroup RR of 0.62 represents a greater relative reduction than the main-analysis RR of 0.64, not a reduction "to a lesser degree."

4 of 4

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.1002/14651858.cd001264

    Major

    The cited work was retracted on 1998-10-26 (notice 10.1002/14651858.cd001264.pub2), before this paper was published (2020-12-08). Its authors could have known.

    Cited work 10.1002/14651858.cd001264 · retracted 1998-10-26 · notice 10.1002/14651858.cd001264.pub2 · this paper published 2020-12-08

1 of 1

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 44

  1. Azim, 2014, Efficacy of probiotics (Saccharomyces bulardii) in acute watery diarrhoea in children, Journal of Rawalpindi Medical College (JRMC), 18, 213
  2. Burki, 2017, Efficacy of Saccharomyces boullardii in children with acute diarrhoea, Medical Forum, 28, 112
  3. Cetina-Sauri, 1994, Evaluation of Saccharomyces boulardii in children with acute diarrhea, Annales de Pediatrie, 41, 397
  4. D'Apuzzo, 1982, The treatment of acute diarrhoea in paediatrics using Streptococcus faecium: results of a double blind trial, Therapeutische Umschau, 39, 1033
  5. Hernandez, 1998, Clinical therapeutic effect of Saccharomyces boulardii on children with acute diarrhea, Revista de Enfermedades Infecciosas en Pediatria, 11, 87
  6. Höchter, 1990, Saccharomyces boulardii in the treatment of acute adult diarrhoea., Münchener Medizinische Wochenschrift, 132, 188
  7. Jasinski, 2002, Efficacy of Lactobacillus GG in oral rehydration solution, Pediatrika, 22, 231
  8. Javeed, 2018, Effect of oral Saccharomyces boulardii supplementation on the duration of acute watery diarrhea in children, Pakistan Journal of Medical and Health Sciences, 12, 212
  9. Khan, 2017, Efficacy of Lactobacillus reuteri in acute watery diarrhea, Medical Forum, 28, 7
  10. Kowalska-Duplaga, 1999, Lactobif, a marketed probiotic product containing Bifidobacterium ruminantium, was not effective in the treatment of acute rotavirus diarrhoea in infants, Gut, 44, 17
  11. Kowalska-Duplaga, 2004, Efficacy of Trilac® in the treatment of acute diarrhoea in infants and young children - a multicentre, randomised, double blind placebo-controlled study, Pediatria Wspolczesna, Gastroenterologia, Hepatologia i Zywienie Dziecka, 6, 295
  12. Sirsat, 2017, Role of Saccharomyces boulardii in management of acute diarrhoea of children - A randomized controlled trial, MedPulse International Journal of Pediatrics, 4, 68
  13. Urganci, 2001, Evaluation of the efficacy of Saccharomyces boulardii in children with acute diarrhoea, Archives of Gastroenterohepatology, 20, 81
  14. Ahmadipour, 2018, Probiotic or zinc, which is more effective in treatment of diarrhea in children?, Journal of Pediatric Gastroenterology and Nutrition Conference: 51st Annual Meeting European Society for Paediatric Gastroenterology, Hepatology and Nutrition, 66, 332
  15. Bellomo, 1979, A new approach for the treatment of enteritides in paediatrics, Médecine et Hygiène, 37, 3781
  16. Bellomo, 1982, Controlled study of Enterococcus LAB strain SF68 in acute enteritis in children with concomitant respiratory infection, Clinica Pediatrica, 64, 219
  17. 1995, Controlled clinical trial of Lacteol Fort Sachet versus furazolidone or berberine in treatment of acute diarrhoea in children, Annales de Pediatrie, 42, 396
  18. Boulloche, 1994, Management of acute diarrhoea in infants and young children. Controlled study of the anti-diarrheal efficacy of killed L. acidophilus (LB strain) versus a placebo and a reference drug (loperamide), Annales de Pediatrie, 41, 457
  19. Cetina-Sauri, 1990, Therapeutic evaluation of children with acute diarrhea, Tribuna Medica, 81, 141
  20. Costa-Ribeiro, 2000, Use of Lactobacillus GG in the treatment of severe, acute diarrhoea in adverse environmental conditions, Journal of Pediatric Gastroenterology and Nutrition, 31 Suppl 2, 251
  21. Costa-Ribeiro, 2000, Prophylactic administration of Lactobacillus GG to children in a daycare center, Journal of Pediatric Gastroenterology and Nutrition, 31 Suppl 2, 252
  22. 2004, Efficacy of Bacillus coagulans tablets in the treatment of acute and chronic diarrhoea, International Journal of Immunotherapy, 20, 17
  23. Frigerio, 1986, A lactic acid producer enterococcus in the prevention of antibiotic-associated diarrhoea and in the treatment of acute diarrhoeal disorders: a double-blind multicentre placebo-controlled clinical trial (Abstract), Digestive Diseases and Sciences, 31 Suppl, 496
  24. Girola, 1995, Efficacy of probiotic preparation with living, freeze-dried lactic acid bacteria and yeast on child diarrhoea, Archivio di Medicina Interna, 47, 61
  25. Grandy, 2010, Probiotics in the treatment of acute rotavirus diarrhoea. A randomized, double-blind, controlled trial using two different probiotic preparations in Bolivian children, BMC Infectious Diseases, 10, 253, 10.1186/1471-2334-10-253 · DOI
  26. Hafeez, 2002, The efficacy of Saccharomyces boulardii in the treatment of acute watery diarrhoea in children: a multicentre randomized controlled trial, Journal of College of Physicians and Surgeons Pakistan, 12, 432
  27. Henker, 2007, Acute diarrhoea in infants and small children. Successful adjuvant therapy with the probiotic Mutaflor, Pädiat. Prax, 71, 605
  28. Jimenez-Rodriguez C Jimenez-Diaz J Hernandez-Martinez F Rodriguez-De-vera B Efficacy of probiotics against acute diarrhoea in warm areas Annals of Nutrition and Metabolism Conference: 9th workshop probiotics and prebiotics 2018
  29. Khan, 2012, Clinical efficacy of use of probiotic “Saccharomyces boulardii” in children with acute watery diarrhea, Pakistan Pediatric Journal, 36, 122
  30. Lahiri, 2015, Beneficial role of probiotic in acute childhood diarrhoea, Journal of Harmonized Research in Medical and Health Science, 2, 26
  31. Mazo, 2006, Efficacy and safety of milk fermented by lactobacillus (kumis) in nutritional recovery of undernourished children and control of their diarrhoea episodes, Revista Facultad Nacional de Salud Pública, 24, 83
  32. Moraes, 2001, A multicentric, randomised, investigator-blind, parallel group study to assess the efficacy, safety and tolerability of Racecadotril versus Saccharomyces boulardii in the treatment of acute diarrhoea in adults, Revista Brasileira de Medicina, 58, 65
  33. Perez, 2019, Coddle study: Bacillus clausii as an adjunctive treatment of acute community-acquired diarrhoea in Filipino children, Journal of Pediatric Gastroenterology and Nutrition, 68, 477
  34. Satoh, 1984, Effect of Bifidobacterium breve administration on clinical course and intestinal flora in children with acute diarrhea [Abstract], Nippon Shonikagakkai Zasshi, 88, 2178
  35. Sepp, 1995, Impact of a Lactobacillus probiotic on the faecal microflora in children with shigellosis, Microecology and Therapy, 23, 74
  36. Simakachorn, 2000, Erratum, Journal of Pediatric Gastroenterology, 30, 228
  37. Singh, 2018, Comparison of clinical efficacy of Saccharomyces boulardii with yogurt in acute watery diarrhea in children, Pakistan Paediatric Journal, 42, 167
  38. Sugita, 1994, Efficacy of Lactobacillus preparation bioloactis powder in children with rotavirus enteritis, Japan Journal of Pediatrics, 47, 2755
  39. Táborská, 1997, Smecta and Lactobacillus acidophilus ND in the treatment of acute diarrhoea in children, Ceskoslovenská Pediatrie, 52, 29
  40. Zareen, 2018, Effects of probiotics in shortening the duration of acute diarrhea; a randomized control study, Pakistan Journal of Medical and Health Sciences, 12, 471
  41. Clarke M Oxman A Optimal search strategy. Cochrane Reviewers' Handbook 4.2 [updated March 2003]; Appendix 5c In: The Cochrane Library. The Cochrane Collaboration. Chichester, UK: John Wiley & Sons, Ltd.; 2003, Issue 3
  42. Schnadower, 2019, Letter: Lactobacillus rhamnosus GG offers no benefit over placebo in children with acute gastroenteritis, Alimentary Pharmacology & Therapeutics, 50, 620, 10.1111/apt.15418 · DOI
  43. Division of Diarrhoeal and Acute Respiratory Disease Control, 1990, The Treatment of Diarrhoea. A Manual for Physicians and Other Senior Health Workers
  44. Department of Child and Adolescent Health and Development, 2005, The Treatment of Diarrhoea: A Manual for Physicians and Other Senior Health Workers

Cited by

Sorted by citations

Related

Authors
Collinson, S., Deans, A., Padua-Zamora, A., Gregorio, G. V., Li, C., Dans, L. F., & Allen, S. J.
Affiliations
  • Liverpool School of Tropical Medicine (GB)
  • Urgent Care; Team Medical; Paraparaumu New Zealand
  • Philippine General Hospital (PH)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2020-12-08
Volume
2020
Issue
12
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd003048.pub4
PMC
PMC8166250
OpenAlex
W4211012807
Semantic Scholar
f70de0a0060e62224515a25e2e66c788a97b0e88
Cited by
153
References
202
Citations by year
2026: 15 · 2025: 26 · 2024: 37 · 2023: 27 · 2022: 25 · 2021: 19 · 2020: 1 · 2012: 1
FWCI
10.47
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
Funders
London School of Hygiene and Tropical Medicine
Topics
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
Keywords
probiotics, acute infectious diarrhea, diarrhea duration, paediatric diarrhoea, hospitalization, adverse events, Lactobacillus, Bifidobacterium, diarrhea treatment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-18.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-18.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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