Vasile Soltesz

The role of bile and bile acids in bacterial translocation in obstructive jaundice in rats.

Male Sprague-Dawley rats were randomly divided into five groups in which group 1 received a sham operation (controls), groups 2-5 underwent common bile duct ligation and transection 14 days before the experiments. Two days prior to the studies, animals in groups 1 and 2 received saline orally, while groups 3-5 received an oral administration of either cholic acid, deoxycholic acid or whole bile. Specimens were taken for bacterial culture, and blood was collected for endotoxin assay. The rate of positive bacterial cultures from mesenteric lymph nodes in jaundiced saline-treated animals was significantly higher (p < 0.05) as compared with both controls and the other jaundiced animals treated with either bile or bile acids. Assays were positive for endotoxin in the jaundiced saline-treated group, whereas they were negative in both controls and bile- or bile-acid-treated animals. We conclude that oral administration of cholic acid, deoxycholic acid or whole bile inhibited bacterial translocation and endotoxin absorption in obstructive jaundice in the rat.

Gut Origin Sepsis, Macrophage Function, and Oxygen Extraction Associated with Acute Pancreatitis in the Rat

Abstract. It has been suggested that the gut plays a role in the development of bacterial complications, which are important contributors to morbidity and mortality in patients with acute pancreatitis. The present study evaluated the enteric bacterial translocation, bacterial homeostasis, and reticuloendothelial system function in experimental acute pancreatitis induced by intraductal injection of 5% sodium taurodeoxycholate in the rat. The incidence of bacterial translocation from the gut to mesenteric lymph nodes (MLNs) and lungs significantly increased after 12 hours and to the systemic circulation, ascites, and pancreas at 24 hours. The number of anaerobic bacteria and lactobacilli decreased in the colon and distal ileum from 6 or 12 hours, whereas the number ofEscherichia coli increased from 12 hours. The systemic uptake rate of radiolabeled bacteria decreased from 6 hours after induction of acute pancreatitis. The uptake of radiolabeled bacteria by Kupffer cells decreased from 6 hours, whereas the uptake by macrophages from blood, lungs, and the intestine increased. A decrease in macrophage killing capacity was noted, reflected by an increase in the number of cultured viable bacteria from isolated macrophages. The whole-body oxygen extraction rate increased 4 to 24 hours after induction of pancreatitis, whereas the gut oxygen extraction rate decreased at 2 and 4 hours, followed by an increase at 12 to 24 hours. These data show that translocation of enteric bacteria occurs during the early stage of acute pancreatitis and that the MLN–thoracic duct–circulation may be a major route of bacterial dissemination. Compromised gut oxygen metabolism, overexaggerated intestinal macrophages, and impaired host immune function may be involved in the development of infectious complications associated with acute pancreatitis.

Bacterial translocation in acute liver failure induced by 90 per cent hepatectomy in the rat

Bacterial infection and bacteraemia have been observed in patients with acute liver failure. The exact source of bacteria and nature of pathophysiological mechanisms explaining the development of infection remain unclear. In the present study, acute liver failure was induced by 90 per cent hepatectomy in the rat. The mesenteric lymph nodes and organs were harvested aseptically for bacteriological culture after sham operation or 90 per cent hepatectomy. Function of the liver and reticuloendothelial system (RES) was assayed; gut oxygen extraction was also measured. Translocation of enteric bacteria occurred 2 h after operation and increased with time following hepatectomy. Overgrowth of Escherichia coli in the distal small intestine started 2 h after operation. RES function decreased immediately after 90 per cent hepatectomy; uptake rates per gram tissue in other organs increased signicantly. These results indicate that bacterial translocation occurred early after 90 per cent hepatectomy, associated with a decrease in RES function and gut oxygen extraction, and overgrowth of intestinal bacteria.

Alterations in intestinal motility and microflora in experimental acute pancreatitis

SummaryConclusionA delay in intestinal transit time appears as an early event in acute pancreatitis, preceding intestinal bacterial overgrowth and translocation.BackgroundSeptic complications, primarily caused by bacteria of enteric origin, are frequent in severe acute pancreatitis. Impairment in intestinal motility probably plays a pathophysiological role in the development of bacterial overgrowth and ensuing translocation.MethodsIn the present study, the influence of acute pancreatitis on intestinal motility was evaluated by measuring small intestinal transit time in the rat. Acute pancreatitis was induced by the retrograde intraductal infusion of 0.2 mL taurodeoxycholate. Intestinal transit time was studied by intraduodenal injection of Krebs’ phosphate-buffered solution labeled with Na251CrCO4, and 1 h small intestinal transit was measured at 1, 3, 12, and 24 h, after induction of pancreatitis. Bacterial overgrowth was evaluated by measuringEscherichia coli counts in the colon and distal small intestine, and bacterial translocation to mesenteric lymph nodes, the liver, spleen, and pancreas was determined.ResultsA delayed small intestinal transit time was noted from 3 h on after induction of acute pancreatitis, with most of the radioactivity retained in the first two intestinal segments. Overgrowth ofE. coli was noted 12 h after induction of pancreatitis in both the colon and distal small intestine, and at the same time-point, a significant increase in the incidence of bacterial translocation to mesenteric lymph nodes was seen.

WATER-SOLUBLE ETHYLHYDROXYETHYL CELLULOSE PREVENTS BACTERIAL TRANSLOCATION INDUCED BY MAJOR LIVER RESECTION IN THE RAT

Enteric bacteria might act as pathogens, translocating across the intestinal barrier to extraintestinal sites after major liver resection. In the current study, water-soluble ethylhydroxyethyl cellulose (EHEC) was administered before hepatectomy to evaluate the influence on bacterial translocation induced by major liver resection, phagocytic capacity by visceral and circulating macrophages, enteric bacterial population, and bacterial adherence on the intestinal surface in rats subjected to sham operation or to 70% or 90% hepatectomy. Oral or intravenous (IV) administration of EHEC reduced the incidence of bacterial translocation to mesenteric lymph nodes (MLN) and blood after major liver resection. Oral EHEC appeared more effective than IV administration in protecting against bacterial translocation to MLN in animals with 90% hepatectomy. Ethylhydroxyethyl cellulose (oral and IV) significantly diminished intestinal macrophage uptake capacity of 125I-labeled, heat-killed Escherichia coli as compared with animals without EHEC administration. Overgrowth or colonization of enteric bacteria after major liver resection could be prevented by oral or IV EHEC. Adherence of 14C-labeled, alive E. coli on the intestinal mucosa decreased after EHEC treatment in animals subjected to major liver resection. Systemic arterial pressure and intestinal blood flow markedly decreased from 1 hour and on after 90% hepatectomy. Intravenous administration of EHEC did not improve these alterations. Bacterial hydrophobicity and surface negative charge were significantly reduced 1 hour after bacterial culture with EHEC. Thus, EHEC appears to be a potent agent preventing translocation of enteric bacteria from the gut after major liver resection, by altering the surface characters of enteric bacteria, balancing the enteric microflora, inhibiting bacterial attachment onto the intestinal surface, and blocking phagocytosis by intestinal macrophages.

Effect of a Platelet-Activating Factor Antagonist on Pancreatitis-Associated Gut Barrier Dysfunction in Rats

Platelet-activating factor (PAF) may play a critical and primary role in the pathogenesis of acute pancreatitis and pancreatitis-associated distant organ injury. The present study evaluated the effect of a PAF antagonist, lexipafant (an (S)-4-methyl-2 (methyl-imidazo {4,5-c} pyridin-l-ylmethyl)-benzenesulphonyl]-amino} pentanoic acid ethyl ester, BB-882; British Biotech Ltd.), on the potential prevention of gut barrier dysfunction, by measuring gut origin sepsis, bidirectional permeability of the intestinal barrier, and pancreatic capillary endothelial barrier integrity, in acute pancreatitis induced by intraductal infusion of 5% sodium taurodeoxycholate. Pancreatic endothelial permeability significantly increased in animals with acute pancreatitis, whereas pretreatment with lexipafant had a preventive effect (p <0.05 vs. pancreatitis with saline). Similarly, alterations noted in hematocrit and plasma levels of lipase and calcium were counteracted by the PAF antagonist. It also prevented the increase in albumin leakage from blood to the mucosal interstitium and from blood to the intestinal lumen in acute pancreatitis. Albumin passage from the gut lumen to blood in animals with pancreatitis pretreated with saline increased from 3 h and on, and lexipafant prevented alterations in mucosal epithelial permeability. Bacterial translocation was commonly seen in pancreatitis, whereas only a few positive cultures were observed in pancreatitis animals given lexipafant. Microthrombosis in intestinal villi seemed less frequent after lexipafant pretreatment. We conclude that (a) PAF may play a role in the pathogenesis of pancreatitis-associated intestional dysfunction, (b) PAF may be involved in the development of distant organ dysfunction by triggering endothelial barrier dysfunction, and (c) PAF antagonists may provide potential agents for preventing pancreatitis-associated gut barrier dysfunction.

The Role of Oral Administration of Oatmeal Fermented by Lactobacillus reuteri R2LC on Bacterial Translocation after Acute Liver Failure Induced by Subtotal Liver Resection in the Rat

BACKGROUND Previous experimental studies showed that a disturbed ecology of the enteric bacterial population might contribute to the occurrence of bacterial translocation from the gut in acute liver failure (ALF). METHODS In the present study the effects of oral administration of exogenous Lactobacillus reuteri R2LC and oat fiber on bacterial overgrowth and translocation and on enterocyte protein contents were investigated in rats with ALF induced by subtotal liver resection. The oatmeal soup base was anaerobically inoculated with L. reuteri R2LC and fermented for 15 h. The animals were then fed with fermented or unfermented oatmeal or saline daily for 6 days before the experimental procedure. RESULTS The incidence of bacterial translocation to the systemic circulation was nil and 17% in rats subjected to sham operation with saline or 90% hepatectomy with fermented oatmeal, respectively, and 80-90% and 34-50% in rats subjected to hepatectomy with saline or unfermented oatmeal. One rat treated with fermented oatmeal had positive bacterial growth in mesenteric lymph nodes (MLN), which was significantly lower than in hepatectomized rats with saline or unfermented oatmeal (80-100% and 50-67%). No significant differences was demonstrable between hepatectomized animals with oral administration of fermented or unfermented oatmeal as compared with sham-operated rats. The number of anaerobic bacteria, Gram-negative anaerobes, and Lactobacillus decreased significantly, and the number of Escherichia coli increased in the distal small intestine and colon in hepatectomized animals with saline or unfermented oatmeal, as compared with animals subjected to sham operation or hepatectomy with fermented oatmeal. CONCLUSIONS The occurrence of bacterial translocation from the gut in 90% hepatectomy-induced ALF could be prevented by fermented oatmeal, which implies possibilities for biologically balancing the enteric bacterial ecology.

Cisapride Prevents Enteric Bacterial Overgrowth and Translocation by Improvement of Intestinal Motility in Rats with Acute Liver Failure

Enteric bacterial overgrowth resulting from compromised gastrointestinal motility has been suggested to be important for the development of enteric bacterial translocation. In the present study, the effect of cisapride, a 5-hydroxytryptamine-4-receptor agonist and stimulant of intestinal motility, was evaluated concerning intestinal motility, as measured by intestinal transit time, enteric bacterial overgrowth, and bacterial translocation from the gut in rats with acute liver failure induced by 90% hepatectomy. The results demonstrated that (1) the incidence of bacterial translocation to the systemic and portal circulation as well as to the liver, spleen, kidneys, and lungs was nil, and 17-33% to MLN in hepatectomized animals treated with cisapride, i.e. significantly lower than in hepatectomized rats administered saline; (2) overgrowth of E. coli in the intestine was noted in hepatectomized animals given saline, but not following cisapride treatment; (3) cisapride improved the otherwise delayed intestinal transit time following hepatectomy as shown by an increase in the leading edge of isotopic propulsion and the linear slope of the cumulative percent of radioactivity through each intestinal segment. Thus, we conclude that intravenous administration of cisapride prevents enteric bacterial overgrowth and bacterial translocation by improving intestinal motility in rats with acute liver failure induced by subtotal hepatectomy.

Cholecystokinin Increases Small Intestinal Motility and Reduces Enteric Bacterial Overgrowth and Translocation in Rats with Surgically Induced Acute Liver Failure

Enteric bacterial translocation into extraintestinal sites has been proposed as a potential route for bacterial infection in acute liver failure. Bacterial overgrowth in the intestine plays an important role in the etiology of bacterial translocation from the gut. The aim of the present study was to evaluate the influence of exogenous cholecystokinin (CCK) on intestinal transit time, enteric bacterial overgrowth and translocation in experimental acute liver failure induced by 90% hepatectomy. A delayed intestinal transit time was noted in animals subjected by subtotal hepatectomy after 1 h, followed by enteric bacterial overgrowth and translocation into the systemic circulation, mesenteric lymph nodes, and systemic organs at 2 and 4 h. Intravenous infusion of CCK stimulated intestinal transit time in animals with sham operation and subtotal hepatectomy, though a restoration to sham levels could not be obtained in the later. Moreover, enteric bacterial overgrowth and translocation were prevented in hepatectomized animals. The present data imply that impaired intestinal motility, followed by enteric bacterial overgrowth and translocation in experimental acute liver failure, could be prevented by CCK infusion.

The Effect of Biliary Decompression on Bacterial Translocation in Jaundiced Rats

Patients with obstructive jaundice are prone to septic complications after biliary tract operations. Restoring bile flow to the intestine may help to decrease the complication rate. The present study is aimed at evaluating the effect of biliary decompression on bacterial translocation in jaundiced rats. Sixty-six male Sprague-Dawley rats were randomly allocated to six groups subjected to common bile duct ligation (CBDL) and transection (groups 2–6) or sham operation (group 1). In groups and 2 the incidence of enteric bacterial translocation was determined 2 weeks after sham operation or CBDL. In groups 3–6, biliary decompression was achieved by performing a choledochoduodenostomy after 2 weeks of biliary decompression. Bacterial translocation was then studied 1,2,3 and 5 weeks following biliary decompression. The rate of bacterial translocation to mesenteric lymph nodes in obstructive jaundice was significantly higher as compared with controls, and decreased with time to nil three weeks following biliary decompression. The incidence of bacterial translocation was closely correlated (r = 0.844; p = 0.034) with serum alkaline phosphatase activity and seemed to fit with the morphological changes noted in the small intestine. The decrease in bacterial translocation, however, lags behind the recovery of liver function as measured by routine liver function tests and antipyrine clearance. Obstructive jaundice thus promotes bacterial translocation in the rat. Biliary decompression gradually decreases the rate of bacterial translocation.