The effects of probiotic supplementation on experimental acute pancreatitis: a systematic review and meta-analysis

PLoS One. 2012;7(11):e48811. doi: 10.1371/journal.pone.0048811. Epub 2012 Nov 13.


Background: In February 2008, the results of the PRObiotics in PAncreatitis TRIAl (PROPATRIA) were published. This study investigated the use of probiotics in patients suffering from severe acute pancreatitis. No differences between the groups were found for any of the primary endpoints. However, mortality in the probiotics group was significantly higher than in the placebo group. This result was unexpected in light of the results of the animal studies referred to in the trial protocol. We used the methods of systematic review and meta-analysis to take a closer look at the relation between the animal studies on probiotics and pancreatitis and the PROPATRIA-trial, focussing on indications for harmful effects and efficacy.

Methods and results: Both PubMed and Embase were searched for original articles concerning the effects of probiotics in experimental acute pancreatitis, yielding thirteen studies that met the inclusion criteria. Data on mortality, bacterial translocation and histological damage to the pancreas were extracted, as well as study quality indicators. Meta-analysis of the four animal studies published before PROPATRIA showed that probiotic supplementation did not diminish mortality, reduced the overall histopathological score of the pancreas and reduced bacterial translocation to pancreas and mesenteric lymph nodes. Comparable results were found when all relevant studies published so far were taken into account.

Conclusions: A more thorough analysis of all relevant animal studies carried out before (and after) the publication of the study protocol of the PROPATRIA trial could not have predicted the harmful effects of probiotics found in the PROPATRIA-trial. Moreover, meta-analysis of the preclinical animal studies did show evidence for efficacy. It may be suggested, however, that the most appropriate animal experiments in relation to the design of the human trial have not yet been conducted, which compromises a fair comparison between the results of the animal studies and the PROPATRIA trial.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Acute Disease
  • Animals
  • Bacterial Translocation
  • Disease Models, Animal
  • Humans
  • Lymph Nodes / microbiology
  • Mesentery
  • Odds Ratio
  • Pancreatitis / mortality
  • Pancreatitis / pathology
  • Pancreatitis / therapy*
  • Probiotics / adverse effects*
  • Probiotics / therapeutic use
  • Publication Bias
  • Risk Assessment

Grants and funding

The ZonMW program 'Dierproeven begrensd' in the Netherlands (ZonMW is a scientific organization for health research and development); Grant No. 114000089 and 114000103 funded this project. ZonMW had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.