Translocated intenstinal bacteria cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiologic evidence

Llovet, Josep M.; Bartolı́, Ramón; March, Francesca; Planas, Ramón; Viñado, Belén; Cabré, Eduard; Arnal, J; Coll, Pere; Ausina, V.; Gassull, Miquel A.

doi:10.1016/0168-8278(88)80018-7

Cited by 141 publications

(96 citation statements)

References 25 publications

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“…One study demonstrated gut bacterial flora in mesenteric lymph nodes of 30.8% of patients with Child's Pugh C cirrhosis, compared with less than 10% in non-cirrhotic patients. 88 These translocated bacteria can either become a direct source of infection, 89 or translocated bacterial products including endotoxins can become a source of chronic inflammation by inducing an immune response. 90 One study showed endotoxemia, without sepsis, was seen in 92.3% of patients with cirrhosis and was completely absent in healthy controls with higher levels of endotoxemia seen in those with HE, and a high level predicted mortality.…”

Section: Systemic Inflammation and Immune Dysfunction In Acute And Chmentioning

confidence: 99%

Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

Aldridge

Tranah

Shawcross

2015

Journal of Clinical and Experimental Hepatology

235

190

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The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. ( J CLIN EXP HEPATOL 2015;5:S7-S20) H epatic encephalopathy (HE) is the term used to encapsulate the broad spectrum of neuropsychiatric disturbances associated with both acute and chronic liver failure (ALF and CLF, respectively), as well as porto-systemic bypass in the absence of hepatocellular disease. The clinical manifestations of HE can be extremely heterogeneous in nature, with symptoms presenting anywhere on a continuum spanning from seemingly normal cognitive performance, right the way through to states of confusion, stupor and coma. In between these extremes, patients with HE may exhibit signs such as inattentiveness, blunted affect, impairment of memory or reversal of the sleep-wake cycle, as well as physical manifestations such as tremor, myoclonus, asterixis and deep tendon hyperreflexia.ALF is defined by the onset of coagulopathy alongside any degree of encephalopathy in patients with no evidence of pre-existing liver disease. 1 The presence of HE in those with ALF is prognostic, with up to a quarter of cases developing raised intracranial pressure. 2 Patients presenting with ALF are at risk of developing its cardinal, lifethreatening feature, cerebral edema. Left untreated, cerebral edema can rapidly progress to cause herniation of the uncus through the falx cerebri, leading to compression of the brainstem and, ultimately, death. H...

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Section: Systemic Inflammation and Immune Dysfunction In Acute And Chmentioning

confidence: 99%

Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

Aldridge

Tranah

Shawcross

2015

Journal of Clinical and Experimental Hepatology

235

190

View full text Add to dashboard Cite

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“…2 BT is considered to be present either in patients or in animal models of cirrhosis when the culture of mesenteric lymph nodes (MLN) shows the growth of at least one bacterial species. 3 The genetic identity of bacteria isolated in ileal content, MLNs, and infected ascitic fluid (AF) in rats with experimental cirrhosis 4 has been shown, which supports the contention of a continuum among intestinal lumen, translocation to MLN, and eventual induction of spontaneous bacterial peritonitis. However, the study of BT is logically difficult in patients with cirrhosis.…”

mentioning

confidence: 94%

The detection of bacterial DNA in blood of rats with CCl4-induced cirrhosis with ascites represents episodes of bacterial translocation

Guarner¹,

González‐Navajas

Sánchez³

et al. 2006

Hepatology

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B acterial translocation (BT) is considered a key event in the pathogenesis of bacterial infections in patients with advanced cirrhosis, 1 and spontaneous bacterial peritonitis is probably the most relevant infection in this setting. 2 BT is considered to be present either in patients or in animal models of cirrhosis when the culture of mesenteric lymph nodes (MLN) shows the growth of at least one bacterial species. 3 The genetic identity of bacteria isolated in ileal content, MLNs, and infected ascitic fluid (AF) in rats with experimental cirrhosis 4 has been shown, which supports the contention of a continuum among intestinal lumen, translocation to MLN, and eventual induction of spontaneous bacterial peritonitis. However, the study of BT is logically difficult in patients with cirrhosis.We have shown that roughly 30% of patients with advanced cirrhosis and AF show the simultaneous presence in blood and AF of fragments of bacterial DNA (bactDNA), mostly from the same type of bacteria, 5 and that these fragments may last in blood during variable periods. 6 The identity of the nucleotide sequences detected in a given patient during the study period, together with the fact that bactDNA may disappear and then reAbbreviations: BT, bacterial translocation; MLN, mesenteric lymph nodes; AF, ascitic fluid; PCR, polymerase chain reaction; TNF-␣, tumor necrosis factor alpha; NOx sum of NO metabolites, nitrite and nitrate. From the

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“…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.…”

mentioning

confidence: 99%

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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Translocated intenstinal bacteria cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiologic evidence

Cited by 141 publications

References 25 publications

Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

The detection of bacterial DNA in blood of rats with CCl4-induced cirrhosis with ascites represents episodes of bacterial translocation

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

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