Elsevier

Surgery

Volume 141, Issue 4, April 2007, Pages 470-480
Surgery

Original communication
Modification of intestinal flora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis

Part of this work was presented at the 13th United European Gastroenterology Week (Copenhagen, Denmark) and was published as an abstract (Gut 2005; suppl VII (54):A24).
https://doi.org/10.1016/j.surg.2006.10.007Get rights and content

Background

Infection of pancreatic necrosis by gut bacteria is a major cause of morbidity and mortality in patients with severe acute pancreatitis. Use of prophylactic antibiotics remains controversial. The aim of this experiment was assess if modification of intestinal flora with specifically designed multispecies probiotics reduces bacterial translocation or improves outcome in a rat model of acute pancreatitis.

Methods

Male Sprague-Dawley rats were allocated into 3 groups: (1) controls (sham-operated, no treatment), (2) pancreatitis and placebo, and (3) pancreatitis and probiotics. Acute pancreatitis was induced by intraductal glycodeoxycholate and intravenous cerulein infusion. Daily probiotics or placebo was administered intragastrically from 5 days prior until 7 days after induction of pancreatitis. Tissue and fluid samples were collected for microbiologic and quantitative real-time PCR analysis of bacterial translocation.

Results

Probiotics reduced duodenal bacterial overgrowth of potential pathogens (Log10 colony-forming units [CFU]/g 5.0 ± 0.7 [placebo] vs 3.5 ± 0.3 CFU/g [probiotics], P < .05), resulting in reduced bacterial translocation to extraintestinal sites, including the pancreas (5.38 ± 1.0 CFU/g [placebo] vs 3.1 ± 0.5 CFU/g [probiotics], P < .05). Accordingly, health scores were better and late phase mortality was reduced: 27% (4/15, placebo) versus 0% (0/13, probiotics), respectively, P < .05.

Conclusions

This experiment supports the hypothesis that modification of intestinal flora with multispecies probiotics results in reduced bacterial translocation, morbidity, and mortality in the course of experimental acute pancreatitis.

Section snippets

Animals

Male, pathogen-free Sprague-Dawley rats, 250 to 350 grams, (Harlan, Horst, The Netherlands) were kept under constant housing conditions (temperature, 22°C; relative humidity, 60%; and a 12-hour light/dark cycle) and had free access to water and food (RMH 1110, Hope Farms, Woerden, The Netherlands) throughout the experiment. Rats were allowed to adjust to these conditions for 1 week prior to surgery. The experimental design shown in Fig 1 was approved by the institutional animal care committee

Morbidity and mortality

After the start of daily placebo or probiotic administrations, physical behavior of all rats remained normal, resulting in maximal health scores from day -5 until day 0. The clinical response of the rats after induction of experimental pancreatitis followed a biphasic course. During the first 72 hours, the animals exhibited decreased grooming or motility and, to some extent, behavior associated with pain, despite analgesic administration during the first 48 hours. From days 3 to 5, surviving

Discussion

This is the first study to assess the potential of a specifically designed multispecies probiotic mixture to reduce bacterial translocation during acute pancreatitis. In this paper, we demonstrate that modification of intestinal flora with this probiotic mixture alters the course of experimental acute pancreatitis. Administration of the selected probiotic mixture resulted in the following: (1) reduced duodenal overgrowth of pathogens, such as E. coli; (2) reduced bacterial translocation to

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    Supported in part by Astra Zeneca, Research & Development, Mölndal, Sweden (L.P.M.); Winclove Bio Industries B.V., Amsterdam, The Netherlands (H.M.T.); and Senter, an agency of the Dutch Ministry of Economic Affairs (grant number: TSGE3109). Supporting institutions were not involved in design, performance or publication of this study.

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