Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, the Netherlands.
Department of Surgery, Division of Pediatric Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands.
Nat Biotechnol. 2016 Jan;34(1):55-63. doi: 10.1038/nbt.3436.
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.
PROPATRIA（益生菌治疗胰腺炎试验）是一项多中心、双盲、安慰剂对照的临床试验，旨在通过肠内使用多种益生菌制剂来减少预测为重症急性胰腺炎患者的感染性并发症。令人惊讶的是，在接受益生菌治疗的 152 名患者中有 24 名（16%）死亡，而在安慰剂组的 144 名患者中有 9 名（6%）死亡。与之前较小的研究和我们对短肠综合征（SSB）患者肠道中丰富的乳酸杆菌的观察结果相比，益生菌治疗组的高死亡率形成了强烈对比。我们认为，主要的蛋白水解胰腺酶和益生菌治疗的致命组合导致了 PROPATRIA 试验的高死亡率，而细菌发酵碳水化合物产生的乳酸水平升高是一个关键的促成因素。我们建议，只要未来的临床研究（i）在疾病症状首次出现后立即开始益生菌治疗，（ii）限制可发酵碳水化合物的供应，（iii）防止患者自身肠道菌群的细菌过度生长，（iv）大量增加益生菌细菌的剂量，那么益生菌治疗可能不会对预防与急性胰腺炎相关的继发性感染产生禁忌。
