Small Intestine Dysmotility and Bacterial Overgrowth in Cirrhotic Patients With Spontaneous Bacterial Peritonitis

Chang, Chi-Sen; Chen, Gran‐Hum; Lien, Han‐Chung; Yeh, Hong‐Zen

doi:10.1002/hep.510280504

Cited by 242 publications

(174 citation statements)

References 44 publications

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“…20 Furthermore, the prevalence of SBP was found to be significantly higher in cirrhotic patients with IBO than in those without IBO, 17 and in a recent study the incidence of bacterial overgrowth of the small intestine was significantly higher in cirrhotic patients with SBP than in those without SBP. 25 In the present experimental study, we have observed that total, gram-positive, and gram-negative jejunal IBO and total cecal bacterial overgrowth, were significantly higher in ascitic cirrhotic rats with BT than in those without BT. Moreover, we have observed that BT of a specific organism was almost always associated with IBO of that organism; only one of the bacteria (16%) detected in MLN was not overgrowing in the jejunal contents at the time of laparotomy.…”

Section: Discussionsupporting

confidence: 49%

Effect of cisapride on intestinal bacterial overgrowth and bacterial translocation in cirrhosis

et al. 2000

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Deranged intestinal motility, which occurs in cirrhosis, may facilitate the development of intestinal bacterial overgrowth (IBO), which can lead to bacterial translocation (BT). To assess the effect of cisapride on IBO and BT in cirrhosis, cirrhotic rats received cisapride or a placebo for 7 days, and measurements of jejunal bacterial content and BT studies were performed. In addition, jejunal fluid from 46 cirrhotic patients was obtained for quantitative bacterial culture. Those patients in whom gram-negative IBO was detected were randomized to receive or not to receive cisapride (20 mg twice per day) for 1 week. Cisapride significantly reduced IBO in cirrhotic rats. In addition, no BT was documented in treated animals, whereas it occurred in 40% in nontreated cirrhotic rats. Total IBO was documented in 23 of 46 cirrhotic patients, which was caused by gram-negative organisms in 10 cases. Orocecal transit time (OCT) significantly decreased after cisapride therapy, and was associated with the abolishment of bacterial overgrowth caused by gram-negative organisms in 4 out of 5 treated patients, whereas it persisted in nontreated cases. Cisapride administration to cirrhotic rats resulted in a reduction of the IBO, which is associated with a marked decrease in BT. On the other hand, cisapride facilitates the abolition of IBO caused by gram-negative organisms in cirrhotic patients. (HEPATOLOGY 2000;31:858-863.)

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Section: Discussionsupporting

confidence: 49%

Effect of cisapride on intestinal bacterial overgrowth and bacterial translocation in cirrhosis

et al. 2000

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“…Intestinal hypomotility had not been previously reported in rats with cirrhosis, but our finding agrees with the observation of prolonged small intestinal transit in rats with portal vein stenosis and in patients with cirrhosis. 11,18,22 Moreover, cirrhotic patients with a history of SBP show higher incidence of IBO and more severe small intestine dismotility than cirrhotic patients without a history of SBP. 11 The pathogenesis of these abnormalities in small bowel motility remains speculative and is probably of multifactorial origin.…”

Section: Discussionmentioning

confidence: 99%

“…11,18,22 Moreover, cirrhotic patients with a history of SBP show higher incidence of IBO and more severe small intestine dismotility than cirrhotic patients without a history of SBP. 11 The pathogenesis of these abnormalities in small bowel motility remains speculative and is probably of multifactorial origin. Sympathetic stimulation, as present in cirrhosis with ascites, delays intestinal transit, an effect that seems to be modulated by a ␤-adrenoceptor-mediated pathway.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, intestinal bacterial overgrowth (IBO) by gram-negative aerobes has been observed in patients with alcohol-induced cirrhosis and in ascitic cirrhotic rats with BT, 9,10 and its possible relationship with gut motor dysfunction has recently been suggested. 11 Portal hypertension in itself also causes structural changes in the bowel wall that may disrupt the gut barrier and favor BT. 6,8,12 Strategies to reduce the enteric bacterial load of the bowel and the rate of BT in patients and in experimental models of cirrhosis have mainly involved selective intestinal decontamination.…”

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confidence: 99%

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Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites

et al. 2000

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Bacterial translocation appears to be an important mechanism in the pathogenesis of spontaneous infections in cirrhosis. Cirrhotic patients are commonly treated with ␤-adrenoceptor blockers, but the impact of this treatment in the factors promoting bacterial translocation has not been investigated. This study was aimed at investigating in cirrhotic rats with ascites the effect of propranolol on intestinal bacterial load, transit, and permeability of the bowel and on the rate of bacterial translocation. Bacterial translocation to mesenteric lymph nodes and intestinal bacterial overgrowth, permeability (urinary excretion of 99m Tc-diethylenetriaminepentaacetic acid [ 99m Tc-DTPA]), and transit (geometric center ratio of 51 Cr) were assessed in 29 rats with carbon tetrachloride (CCl 4 ) cirrhosis and 20 controls. These variables were then measured in 12 placebo-and in 13 propranolol-treated ascitic cirrhotic rats. Bacterial translocation was present in 48% of the cirrhotic rats and in none of the controls. Cirrhotic rats with intestinal bacterial overgrowth had a significantly higher rate of translocation and slower intestinal transit than those without it. Among the 15 rats with overgrowth and a 99m Tc-DTPA excretion greater than 10%, 15 had translocation and 2 had bacterial peritonitis. Only 1 of the 14 rats with either intestinal overgrowth or a 99m Tc-DTPA excretion greater than 10% presented translocation. Compared with the placebo group, propranolol-treated animals had significantly lower portal pressure, faster intestinal transit, and lower rates of bacterial overgrowth and translocation. In ascitic cirrhotic rats, bacterial translocation results from intestinal overgrowth and severe damage to gut permeability. In this setting, intestinal overgrowth is associated with intestinal hypomotility. Propranolol accelerates the intesti- Cirrhotic patients are prone to bacterial infections, with spontaneous bacterial peritonitis (SBP) being the most characteristic. Clinical and experimental evidence indicates that translocation of bacteria from the intestinal lumen to the bloodstream is directly involved in the pathogenesis of these spontaneous infections. SBP is caused predominantly by enteric organisms, 1 and selective intestinal decontamination lowers the rate of first or recurrent SBP in cirrhotic patients. 2 Studies in carbon tetrachloride (CCl 4 )-induced cirrhotic rats have shown the frequent, simultaneous presence of bacterial translocation (BT) and SBP caused by enteric organisms, 3-5 a higher rate of BT in ascitic than in nonascitic animals, 6 frequent genotype identity between ileal flora and bacteria colonizing the mesenteric lymph nodes (MLN), 7 and a reduction, by selective intestinal decontamination, in the incidence of BT after hemorrhagic shock. 8 The factors that favor BT in cirrhosis are incompletely understood. Proposed mechanisms include disruption of the equilibrium of normal intestinal bacterial flora, increased permeability of the intestinal mucosal barrier, and deficiencies in host immune def...

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“…11 Cirrhosis is also associated with increased permeability of the intestinal mucosal barrier and facilitated bacterial translocation into the portal vein. 12,13 We previously reported that human HSCs expressed TLR4 and CD14, and showed a strong inflammatory reaction in response to lipopolysaccharide (LPS), a major cellular component of gram-negative bacteria. 14 LPS-induced HSC and Kupffer cell activation is now regarded as an important mechanism of liver injury, especially in alcoholic liver diseases.…”

mentioning

confidence: 99%

Hepatic stellate cells primed with cytokines upregulate inflammation in response to peptidoglycan or lipoteichoic acid

Paik

Lee

et al. 2006

Laboratory Investigation

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Gram-positive bacterial products such as peptidoglycan (PGN) and lipoteichoic acid (LTA) are potent stimulators of innate inflammatory responses. We previously reported that lipopolysaccharide (LPS), a major biologically active agent of gram-negative bacteria, induces a proinflammatory response via the Toll-like receptor (TLR) 4 in hepatic stellate cells (HSCs). Here we investigated the mechanism of proinflammatory action by PGN and LTA in activated human HSCs. Following treatment with either TNF-a or IL-1b, expression of TLR2 and CD14 was determined by real-time PCR and Western blotting. NF-jB activation was assessed by NF-jBdriven luciferase assay and electrophoretic mobility shift assay. Interleukin-8 (IL-8) from culture supernatant was measured by ELISA. Activated human HSCs express TLR2 and CD14, which are receptors for PGN and LTA signaling. TNF-a and IL-1b significantly upregulated the expression of TLR2 mRNA and protein in HSCs. PGN and LTA induced NF-jB activation and stimulated production of IL-8 in HSCs. Pretreatment with TNF-a or IL-1b augmented NF-jB activation and IL-8 production in response to PGN or LTA. Both PGN-and LTA-induced NFjB activation and IL-8 secretion were completely inhibited by anti-TLR2 blocking antibody (T2.5). These findings suggest that TNF-a or IL-1b primed HSCs enhance the production of IL-8 in response to PGN and LTA through augmentation of the TLR2 system.

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Small Intestine Dysmotility and Bacterial Overgrowth in Cirrhotic Patients With Spontaneous Bacterial Peritonitis

Cited by 242 publications

References 44 publications

Effect of cisapride on intestinal bacterial overgrowth and bacterial translocation in cirrhosis

Effect of cisapride on intestinal bacterial overgrowth and bacterial translocation in cirrhosis

Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites

Hepatic stellate cells primed with cytokines upregulate inflammation in response to peptidoglycan or lipoteichoic acid

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