A reassessment of the PROPATRIA study and its implications for probiotic therapy

Abstract

The PROPATRIA (Probiotics in Pancreatitis Trial) study was a multicenter, double-blind, placebo-controlled clinical trial that aimed to reduce infectious complications in patients with predicted severe acute pancreatitis by the enteral use of a multispecies probiotic preparation. An unprecedented 24 of 152 patients (16%) in the group receiving probiotics died versus 9 of 144 (6%) in the placebo group. This high mortality rate in the probiotic-treated group contrasts strongly with observations from a previous smaller study and from our observations regarding the effects of abundant intestinal lactobacilli in patients with short small bowel (SSB) syndrome. We argue here that a lethal combination of mainly proteolytic pancreas enzymes and probiotic therapy resulted in the high mortality rate of the PROPATRIA trial and that elevated levels of lactic acid produced by bacterial fermentation of carbohydrates were a key contributing factor. We suggest that probiotic therapy may not be counter-indicated for the prevention of secondary infections associated with acute pancreatitis, provided that future clinical studies (i) start probiotic therapy immediately after first onset of disease symptoms, (ii) limit the supply of fermentable carbohydrates, (iii) prevent bacterial (over)growth of patient's own intestinal flora and (iv) massively increase the dose of probiotic bacteria.

Microbiota-Oriented Diagnostics and Therapy in Sepsis: Utopia or Necessity?

“…The colleagues associated high mortality in PROPATRIA study with lethal combination of proteolytic enzymes of pancreas and high level of lactic acid caused by bacterial fermentation of carbohydrates as a key factor related to intake of probiotics. Nevertheless, authors suggest that a probiotic therapy may not be counterindicated for the prevention of secondary infections associated with acute pancreatitis, provided that future clinical studies start probiotic therapy early as possible and prevent bacterial overgrowth not only of patient's own intestinal flora but also the dose of probiotic bacteria [38].…”

Prospects for microbiota-oriented therapy in neurorehabilitology

“…Коллеги ассоциировали высокую летальность в исследовании PROPATRIA со смертельной комбинацией протеолитических ферментов поджелудочной железы и высоким уровнем молочной кислоты в результате бактериальной ферментации углеводов как ключевого фактора, связанного с приемом пробиотиков. При этом авторы считают, что пробиотическая терапия не является противопоказанием для профилактики вторичных инфекций, связанных с острым панкреатитом, при соблюдении ряда условий: раннего начала пробиотической терапии (сразу после первого появления симптомов болезни), ограничения поставки ферментируемых углеводов и предотвращения чрезмерного роста собственной кишечной флоры пациента [24].…”

Acid lactic lactobacilli as a biotechnological toll to improve food quality and human health

“…A wrong administration or dose for patients with a compromised immune system may cause bacterial sepsis by blood infection . Some studies have reported an increase in human mortality due to the consumption of multispecies probiotic foods (Figure ) . However, their beneficial effects can still be the future of biotechnology.…”

“…105 Some studies have reported an increase in human mortality due to the consumption of multispecies probiotic foods (Figure 3). 106,107 However, their beneficial effects can still be the future of biotechnology.…”