Intestinal barrier dysfunction in a randomized trial of a specific probiotic composition in acute pancreatitis.
OBJECTIVE
To determine the relation between intestinal barrier dysfunction, bacterial translocation, and clinical outcome in patients with predicted severe acute pancreatitis and the influence of probiotics on these processes.


BACKGROUND
Randomized, placebo-controlled, multicenter trial on probiotic prophylaxis (Ecologic 641) in patients with predicted severe acute pancreatitis (PROPATRIA).


METHODS
Excretion of intestinal fatty acid binding protein (IFABP, a parameter for enterocyte damage), recovery of polyethylene glycols (PEGs, a parameter for intestinal permeability), and excretion of nitric oxide (NOx, a parameter for bacterial translocation) were assessed in urine of 141 patients collected 24 to 48 h after start of probiotic or placebo treatment and 7 days thereafter.


RESULTS
IFABP concentrations in the first 72 hours were higher in patients who developed bacteremia (P = 0.03), infected necrosis (P = 0.01), and organ failure (P = 0.008). PEG recovery was higher in patients who developed bacteremia (PEG 4000, P = 0.001), organ failure (PEG 4000, P < 0.0001), or died (PEG 4000, P = 0.009). Probiotic prophylaxis was associated with an increase in IFABP (median 362 vs. 199 pg/mL; P = 0.02), most evidently in patients with organ failure (P = 0.001), and did not influence intestinal permeability. Overall, probiotics decreased NOx (P = 0.05) but, in patients with organ failure, increased NOx (P = 0.001).


CONCLUSIONS
Bacteremia, infected necrosis, organ failure, and mortality were all associated with intestinal barrier dysfunction early in the course of acute pancreatitis. Overall, prophylaxis with this specific combination of probiotic strains reduced bacterial translocation, but was associated with increased bacterial translocation and enterocyte damage in patients with organ failure.
Besselink
Marc G
MG
Department of Surgery, University Medical Center Utrecht, Utrecht.
van Santvoort
Hjalmar C
HC
Renooij
Willem
W
de Smet
Martin B
MB
Boermeester
Marja A
MA
Fischer
Kathelijn
K
Timmerman
Harro M
HM
Ahmed Ali
Usama
U
Cirkel
Geert A
GA
Bollen
Thomas L
TL
van Ramshorst
Bert
B
Schaapherder
Alexander F
AF
Witteman
Ben J
BJ
Ploeg
Rutger J
RJ
van Goor
Harry
H
van Laarhoven
Cornelis J
CJ
Tan
Adriaan C
AC
Brink
Menno A
MA
van der Harst
Erwin
E
Wahab
Peter J
PJ
van Eijck
Casper H
CH
Dejong
Cornelis H
CH
van Erpecum
Karel J
KJ
Akkermans
Louis M
LM
Gooszen
Hein G
HG
D000208:Acute Disease; D016470:Bacteremia / Q000150:complications / Q000175:diagnosis / Q000517:prevention & control; D018988:Bacterial Translocation; D004311:Double-Blind Method; D020895:Enterocytes / Q000473:pathology; D050556:Fatty Acid-Binding Proteins / Q000652:urine; D006801:Humans; D007422:Intestines / Q000473:pathology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000652:urine; D010195:Pancreatitis / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*; D010539:Permeability; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D019936:Probiotics / Q000627:therapeutic use*
D050556:Fatty Acid-Binding Proteins; D009569:Nitric Oxide; D011092:Polyethylene Glycols