Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis

Bauer, Tilman; Steinbrückner, Bernhard; Brinkmann, Folke; Ditzen, Anette; Schwacha, H; Aponte, John J.; Pelz, Klaus; Kist, Manfred; Blum, Hubert E.

doi:10.1111/j.1572-0241.2001.04668.x

Cited by 229 publications

(75 citation statements)

References 27 publications

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“…More recently, the chronic use of PPI has been associated with community-acquired Clostridium difficile colitis [11] and a meta-analysis found an association with acid suppression and enteric infection [12]. Similarly, in two retrospective human studies, the crude odds ratio for development of spontaneous bacterial peritonitis among PPI users versus nonusers ranged from 1.22 to 7.0 [8,13]. A human study by Narula et al found that transgastric instrumentation contaminates the peritoneal cavity and those patients on PPIs have a higher bacterial load compared with nonusers [7].…”

Section: Discussionmentioning

confidence: 99%

The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures

et al. 2009

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Background During transgastric natural orifice transluminal endoscopic surgery (NOTES), there is an iatrogenic perforation of the gastric wall with leakage of gastric contents into the peritoneal cavity. The aim of this study is to determine the effect of proton-pump inhibitors (PPI) and alterations of gastric pH on infection during transgastric surgery. Methods Thirty 250-g male Sprague-Dawley rats were divided into a study group (SG, n = 15) and a control group (CG, n =15). SG were given 5 mg/kg pantoprazole for 3 days before procedure and another dose 1 h before. CG received saline at similar time points. A mini-laparotomy with gastrotomy was performed. Aspiration of 2.0 cc gastric contents was removed from the stomach and injected into the peritoneal cavity of both groups. Gastric pH and peritoneal pH levels were obtained. Gastric aspirate was sent for culture. White blood cell counts (WBC) were obtained on postoperative days 1, 7, and 14, and C-reactive protein (CRP) levels were obtained on postoperative day 1. At day 14, a necropsy was performed and aerobic and anaerobic cultures of the peritoneal cavity were obtained. Results There were no deaths in either group. The average gastric pH in the SG was 5.13 versus 3.26 (p = 0.03) in the CG. The average peritoneal pH was similar in both groups. The WBC in the SG was 4.5 vs. 3.5 (1,000 cells/ mm) in the CG. There was no elevation in CRP levels in either group. Bacterial cultures were positive in 3/15 (20%) rats in the CG and in 9/15 (60%) in the SG (p = 0.008). Intra-abdominal abscesses were found in 2/15 (13%) rats in the CG and in 5/15 (33%) in the SG (p = 0.08). Conclusions Pretreatment with a PPI resulted in a higher rate of peritoneal bacterial contamination and abscess formation. The acidic environment of the stomach appears to be protective against infection when intraperitoneal contamination occurs as a result of gastrotomy.

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Section: Discussionmentioning

confidence: 99%

The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures

et al. 2009

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“…Increased fecal counts of streptococci, comparable to those of coliforms, and a high prevalence of small intestinal bacterial overgrowth with Gram-positive bacteria have been reported in patients with cirrhosis. [24][25][26] Increased extraintestinal translocation of Gram-positive bacterial antigens would be expected in such circumstances, given experiences in experimental animals. 43,44 Indeed, lipoteichoic acid, a component of Gram-positive bacteria, has recently been found in liver tissue of cirrhotic patients, presumably as a consequence of extraintestinal translocation from the gut lumen.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Blood Mononuclear Cell Expression of Toll–Like Receptors and Relation to Cytokine Levels in Cirrhosis

et al. 2003

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Activation of macrophages by endotoxin is assumed responsible for increased circulating tumor necrosis factor ␣ (TNF-␣) and soluble TNF receptor (sTNFR) levels in cirrhosis. Relevant to this is expression of Toll-like receptor (TLR) 4 and TLR2, which is critically involved in production of TNF-␣ in response to endotoxin and Gram-positive microbial stimuli, respectively. The first studies on this in cirrhosis are reported here. In 36 cirrhotic patients and 32 controls, we measured (1) circulating endotoxin, TNF-␣, and sTNFR levels; (2) peripheral blood mononuclear cell (PBMC) expression of TLR4 and TLR2, and (3) in vitro TNF-␣ production by PBMCs stimulated with endotoxin or Staphylococcus aureus enterotoxin B (SEB). PBMC expression of TLR2, circulating TNF-␣ levels, and in vitro TNF-␣ production were reassessed after supplementation with a synbiotic regimen known to increase intestinal levels of Gram-positive bacteria. Endotoxin, TNF-␣, and sTNFR levels were significantly increased in cirrhosis. Endotoxin levels did not correlate significantly with other parameters. PBMC expression of TLR2 but not TLR4 was significantly up-regulated in cirrhosis and correlated significantly with serum TNF-␣ and sTNFR levels. In vitro TNF-␣ production by PBMCs stimulated by SEB was significantly blunted. Supplementation with the synbiotic regimen resulted in significant up-regulation of PBMC expression of TLR2. Serum TNF-␣ levels were further increased and in vitro TNF-␣ production further reduced in most patients. In conclusion, up-regulation of PBMC expression of TLR2 but not TLR4 occurs in cirrhosis, which implies, contrary to previous assumptions, an important stimulatory role for Gram-positive microbial components but not endotoxin. TLR2 likely contributes to increased circulating TNF-␣ and sTNFR levels in cirrhosis.

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“…In cirrhotic patients, in addition, there is bacterial overgrowth in the small intestine. [11][12][13][14][15] Bacteria deconjugate bile acids, 16 and bacterial deconjugation should result in a further reduction in bile acid concentration because unconjugated bile acids are rapidly absorbed by nonionic diffusion. Finally, studies have indicated there is increased small intestinal permeability in cirrhosis, [17][18][19][20] raising the possibility that even conjugated bile acids, which are membrane-impermeable in health, might be absorbed passively.…”

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confidence: 99%

Oral Bile Acids Reduce Bacterial Overgrowth, Bacterial Translocation, and Endotoxemia in Cirrhotic Rats

et al. 2003

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Experiments were performed to test whether conjugated bile acid administration would decrease bacterial overgrowth, bacterial translocation, and endotoxemia in ascitic cirrhotic rats. Cholylsarcosine, a deconjugation-dehydroxylation resistant and cholylglycine, a deconjugation-dehydroxylation susceptible bile acid were used. Rats with CCl 4 -induced cirrhosis and ascites were fed cholylsarcosine, cholylglycine (both at 70 mg/kg/d), or placebo for 2 weeks. Healthy rats, as controls, were treated similarly. In cirrhotic rats receiving placebo, bile secretion from an acute biliary fistula was lower than in healthy rats (27.2 ؎ 6.5 vs. 53.0 ؎ 3.1 L/kg/min; mean ؎ SE, P < .05). The administration of conjugated bile acids to cirrhotic rats normalized bile secretion (cholylsarcosine, 51.8 ؎ 6.29; cholylglycine, 52.72 ؎ 8.9 L/kg/min). Total ileal bacterial content was 6-fold higher in ascitic cirrhotic rats than in healthy rats. Conjugated bile acid administration reduced bacterial content to normal levels. Bacterial translocation was less in cirrhotic animals receiving conjugated bile acids (cholylsarcosine, 33%; cholylglycine, 26%) than in animals receiving placebo (66%). Endotoxemia was decreased in cirrhotic rats by conjugated bile acid feeding (cholylsarcosine, 0.098 ؎ 0.002; cholylglycine 0.101 ؎ 0.007 EU/mL) compared with placebo (0.282 ؎ 0.124, P < .001). Survival was greater in animals receiving conjugated bile acids (cholylsarcosine, 10/15; cholylglycine, 11/15; placebo, 5/15). In conclusion, the administration of conjugated bile acids to ascitic cirrhotic rats increased bile acid secretion, eliminated intestinal bacterial overgrowth, decreased bacterial translocation, decreased endotoxemia, and increased survival. Oral conjugated bile acids may be useful in preventing bacterial translocation, endotoxemia, and spontaneous bacterial perotonitis in cirrhotic patients. (HEPATOLOGY 2003;37:551-557.)

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Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis

Cited by 229 publications

References 27 publications

The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures

The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures

Peripheral Blood Mononuclear Cell Expression of Toll–Like Receptors and Relation to Cytokine Levels in Cirrhosis

Oral Bile Acids Reduce Bacterial Overgrowth, Bacterial Translocation, and Endotoxemia in Cirrhotic Rats

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