Intestinal permeability in a patient with liver cirrhosis

Valadez, Jonathan Manuel Aguirre; Rivera-Espinosa, Liliana; Méndez-Guerrero, Osvely; Chávez‐Pacheco, Juan Luis; Juárez, Ignacio; Torre, Aldo

doi:10.2147/tcrm.s115902

Cited by 38 publications

(29 citation statements)

References 142 publications

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“…Patients with cirrhosis and upper gastrointestinal hemorrhage have increased risk of bacterial infections, particularly SBP, during the first 7 days. 81 Plasma endotoxin levels and intestinal permeability were reported to be increased after variceal hemorrhage. 36 , 82 The latter was identified as an independent predictor for proven or possible infections by multivariate analysis.…”

Section: Gut Impact On Various Cirrhotic Complicationsmentioning

confidence: 99%

Gut Microbiome-based Therapeutics in Liver Cirrhosis: Basic Consideration for the Next Step

Fukui

2017

JCTH

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Infections account for significant morbidity and mortality in liver cirrhosis and most are related to the gut microbiome. Fecal dysbiosis, characterized by an overgrowth of potentially pathogenic bacteria and a decrease in autochthonous non-pathogenic bacteria, becomes prominent with the progression of liver cirrhosis. In cirrhotic patients, disruption of the intestinal barrier causes intestinal hyperpermeability (i.e. leaky gut), which is closely related to gut dysmotility, dysbiosis and small intestinal bacterial overgrowth and may induce pathological bacterial translocation. Although the involved microbial taxa are somewhat different between the cirrhotic patients from the East and the West, the common manifestation of a shortage of bacteria that contribute to the production of short-chain fatty acids and secondary bile acids may facilitate intestinal inflammation, leaky gut and gut dysbiosis. Translocated endotoxin and bacterial DNA are capable of provoking potent inflammation and affecting the metabolic and hemodynamic systems, which may ultimately enhance the progression of liver cirrhosis and its various complications, such as hepatic encephalopathy (HE), variceal bleeding, infection and renal disturbances. Among studies on the microbiome-based therapeutics, findings of probiotic effects on HE have been contradictory in spite of several supportive results. However, the effects of synbiotics and prebiotics are substantially documented. The background of their effectiveness should be evaluated again in relation to the cirrhosis-related changes in gut microbiome and their metabolic effects. Strict indications for the antibiotic rifaximin remain unestablished, although its effect is promising, improving HE and other complications with little influence on microbial populations. The final goal of microbiome-based therapeutics is to adjust the gut-liver axis to the maximal benefit of cirrhotic patients, with the aid of evolving metagenomic and metabolomic analyses.

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Section: Gut Impact On Various Cirrhotic Complicationsmentioning

confidence: 99%

Gut Microbiome-based Therapeutics in Liver Cirrhosis: Basic Consideration for the Next Step

Fukui

2017

JCTH

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“…Liver TLRs are reported to be important determinants of HE severity and are intimately related to arterial ammonia concentration and levels of circulating pro-inflammatory mediators[ 37 - 39 ]. Additionally, tight junction proteins (Occludin and Claudins) are implicated in the regulation of intestinal permeability[ 40 , 41 ].…”

Section: Resultsmentioning

confidence: 99%

Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction

Wang

Zhang

Huang

et al. 2017

WJG

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AIMTo investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl4)-induced acute hepatic dysfunction.METHODSA rat model of HE was established with CCl4. Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was examined.RESULTSFMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating pro-inflammatory factors such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment.CONCLUSIONFMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.

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“…However, in patients with hepatic impairment (especially patients with Child‐Pugh C or MELD >25), systemic absorption increases 5. The reasons behind this are multifactorial, including increased intestinal permeability due to alterations in the mucosal barrier, inflammation, and changes in the gut microbiota 6. Cirrhosis also alters the functional ability of p‐glycoprotein, an important efflux pump that transports drugs and toxins out of cells and into the GI lumen, renal tubule, and bile duct 7.…”

Section: Discussionmentioning

confidence: 99%