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Cited by 164Meta-analysis and systematic reviewsProbiotics and Fermented FoodsStatistical Methods in Clinical Trials

Harms Reporting in Randomized Controlled Trials of Interventions Aimed at Modifying Microbiota: A Systematic Review

Bafeta, Aïda, Koh, Mitsuki, Riveros, Carolina, Ravaud, Philippe·2018·Annals of Internal Medicine
DOI 10.7326/m18-0343
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Abstract

Background: Probiotics, prebiotics, and synbiotics are used increasingly, although the safety and potential harms of these interventions are poorly understood. Purpose: To examine how harms-related information is reported in publications of randomized controlled trials (RCTs) of probiotics, prebiotics, and synbiotics. Data Sources: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science (without language restrictions) from 1 January 2015 to 20 March 2018. Study Selection: RCTs assessing the safety or efficacy of at least 1 intervention involving probiotics, prebiotics, or synbiotics alone or in combination with another intervention compared with any control (such as a placebo or an antibiotic) for any clinical condition. Data Extraction: 4 reviewers independently assessed study characteristics, the reporting of harms, and the presentation of safety results. Data Synthesis: Of 384 trials conducted in healthy volunteers (n = 136) or patients with any of several medical conditions (n = 248), 339 (88%) were published in specialty journals. Trials most often evaluated probiotics (n = 265 [69%]). Studies in persons with medical conditions enrolled outpatients (n = 195) and high-risk patients (n = 53). No harms-related data were reported for 106 trials (28%), safety results were not reported for 142 (37%), and the number of serious adverse events (SAEs) per study group was not given for 309 (80%). Of 242 studies mentioning harms-related results, 37% (n = 89) used only generic statements to describe AEs and 16% (n = 38) used inadequate metrics. Overall, 375 trials (98%) did not give a definition for AEs or SAEs, the number of participant withdrawals due to harms, or the number of AEs and SAEs per study group with denominators. Limitation: Journal publication processes may have affected the completeness of reporting; only English-language publications were examined. Conclusion: Harms reporting in published reports of RCTs assessing probiotics, prebiotics, and synbiotics often is lacking or inadequate. We cannot broadly conclude that these interventions are safe without reporting safety data. Primary Funding Source: No specific funding.

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  • The unknown incidence of probiotic-associated infections is due to lack of systematic reporting of adverse effects during clinical trials and inefficiency of post-registration harm detection.

    “This is due to the lack of systematic reporting on adverse effects during clinical trials and the inefficiency of existing mechanisms for detecting harm after probiotic product registration [78].”

    From Current Concepts in Probiotic Safety and Efficacy (2026) · cites this paper as [78]

  • The presence of such ARGs and VFs may have clinical relevance, particularly in immunocompromised individuals or those with disrupted gut barriers, where opportunities for opportunistic infection or horizontal gene transfer may be increased.

    “The presence of such ARGs and VFs may have clinical relevance, particularly in immunocompromised individuals or those with disrupted gut barriers, where opportunities for opportunistic infection or horizontal gene transfer may be increased.22,29-35”

    From Safety and efficacy concerns in Indian probiotics: Insights from whole-genome sequencing and <i>in vitro</i> assessment (2026) · cites this paper as [34]

  • Probiotic strains may carry transferable antibiotic resistance genes, and underreporting of adverse effects in trials hinders risk evaluation.

    “Probiotic strains may carry transferable antibiotic resistance genes,22,33 and underreporting of adverse effects in trials hinders risk evaluation.34”

    From Safety and efficacy concerns in Indian probiotics: Insights from whole-genome sequencing and <i>in vitro</i> assessment (2026) · cites this paper as [34]

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Authors
Bafeta, A., Koh, M., Riveros, C., & Ravaud, P.
Affiliations
  • Inserm (FR)
  • Columbia University (US)
ORCID
Venue
Annals of Internal Medicine
Publisher
American College of Physicians
Published
2018-08-21
Volume
169
Issue
4
Pages
240-247
ISSN
  • 0003-4819 (ISSN-L)
  • 1539-3704
DOI
10.7326/m18-0343
OpenAlex
W2883808454
Cited by
162
References
53
Citations by year
2026: 15 · 2025: 15 · 2024: 15 · 2023: 19 · 2022: 21 · 2021: 16 · 2020: 25 · 2019: 27 · 2018: 8 · 2017: 1
FWCI
3.74
Type
journal article
Language
en
Open access
closed
Licence
www.acpjournals.org/journal/aim/text-and-data-mining (tdm)
Locations
  • Annals of Internal Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Keywords
harms reporting, probiotics, prebiotics, synbiotics, adverse events, serious adverse events, safety reporting, reporting quality, randomized controlled trials, participant withdrawal
MeSH terms
Humans, Publishing, Research Design, Randomized Controlled Trials as Topic, Probiotics, Prebiotics, Synbiotics, Microbiota

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