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

Carlijn R Hooijmans, Rob B M de Vries, Maroeska M Rovers, Hein G Gooszen, Merel Ritskes-Hoitinga, Carlijn R Hooijmans, Rob B M de Vries, Maroeska M Rovers, Hein G Gooszen, Merel Ritskes-Hoitinga

Abstract

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flow diagram of the systematic…
Figure 1. Flow diagram of the systematic review and meta-analysis literature search results.
Figure 2. Risk of bias, averaged per…
Figure 2. Risk of bias, averaged per item.
yes = low risk of bias, no = high risk of bias, ? = unclear risk of bias, n.a. = not applicable.
Figure 3. Effects of probiotic supplementation on…
Figure 3. Effects of probiotic supplementation on mortality in experimental acute pancreatitis.
Forest plot of the data of three included studies. The forest plot displays the OR, 95% confidence interval and relative weight of the individual studies. The diamond indicates the global estimate and its 95% confidence interval.
Figure 4. Effects of probiotic supplementation on…
Figure 4. Effects of probiotic supplementation on histopathological damage to the pancreas in experimental acute pancreatitis.
(a) Forest plot and (b) subgroup analysis of the data of six included studies. The forest plot displays the SMD, 95% confidence interval and relative weight of the individual studies. The diamond indicates the global estimate and its 95% confidence interval.
Figure 5. Effects of probiotic supplementation on…
Figure 5. Effects of probiotic supplementation on bacterial translocation to the pancreas in experimental acute pancreatitis.
(a) Forest plot and (b) subgroup analysis of the data of five included studies. The forest plot displays the OR, 95% confidence interval and relative weight of the individual studies. The diamond indicates the global estimate and its 95% confidence interval. (c) effectsizes and 95% confidence interval of three studies presenting continuous data which were not included in meta-analysis in order to reduce heterogeneity.
Figure 6. Effects of probiotic supplementation on…
Figure 6. Effects of probiotic supplementation on bacterial translocation to the mesenteric lymph nodes (MLN) in experimental acute pancreatitis.
(a) Forest plot and (b) subgroup analysis of the data of eight included experiments. The forest plot displays the OR, 95% confidence interval and relative weight of the individual studies. The diamond indicates the global estimate and its 95% confidence interval. (c) effectsizes and 95% confidence interval of three studies presenting continuous data which were not included in meta-analysis in order to reduce heterogeneity.

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Source: PubMed

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