Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats

Úbeda, María; Lario, M.; Muñoz, L.; Borrero, M.J.; Rodríguez‐Serrano, Macarena; Sánchez-Díaz, Ana Maria; Campo, Rosa del; Lledó, Lourdes; Pastor, Óscar; García‐Bermejo, Laura; Díaz, David; Álvarez‐Mon, Melchor; Albillos, Agustı́n

doi:10.1016/j.jhep.2015.12.010

Cited by 152 publications

(151 citation statements)

References 36 publications

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“…Notably, these results largely confirm and strengthen earlier findings in a cholestatic model of chronic liver disease using bile duct ligation . Similarly to Ubeda et al, an up‐regulation of occludin and zonulin‐1 was observed, but, additionally, the earlier study also documented an abundant ileal expression of the pore‐ forming claudin‐2, which was countered by overexpression of the pore‐ closing claudin‐1 after treatment with OCA . In conjunction to these structural changes, evidence was not only provided for a functional restoration of the intestinal barrier (by measuring transepithial resistance and dextran permeability in full‐thickness intestinal tissue), but the study also confined the effect of FXR agonism to the ileum.…”

supporting

confidence: 88%

“…A recent translational study by Ubeda et al using a rodent model of decompensated cirrhosis has boosted the contemporary growing body of literature substantiating a central role for FXR in the impaired gut‐liver axis and moreover opened the door to therapeutic intervention. The Spanish group used rats with CCl 4 ‐induced cirrhosis with ascites as a model for decompensated cirrhosis with BT (present in 80% of the animals).…”

mentioning

confidence: 99%

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Evolving insights in the pathophysiology of complications of cirrhosis: The farnesoid X receptor (FXR) to the rescue?

2016

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supporting

confidence: 88%

mentioning

confidence: 99%

Evolving insights in the pathophysiology of complications of cirrhosis: The farnesoid X receptor (FXR) to the rescue?

2016

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“…OCA also decreases intestinal infl ammation in various colitis animal models [110]. In an animal model with advanced cirrhosis, treatment with OCA signifi cantly reduced gut bacterial translocation [111]. Additional miR-21 ablation with FXR activation by OCA ameliorated NASH suggesting that a multi-receptor targeting therapy could be the most effective treatment strategy [112].…”

Section: Role Of Fxr Agonist In Nafld Treatmentmentioning

confidence: 99%

Farnesoid X Receptor Agonist as a new treatment option for Non-Alcoholic Fatty Liver disease: A Review

Singh¹,

Kharbanda²

2017

Arch Hepat Res

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“…FXR plays a crucial role in preserving intestinal epithelial integrity and protection from inflammation presumably by repression of NF-κB signaling and modulation of antimicrobial peptide release [108,109]. The commercially available FXR agonist obeticholic acid has recently been reported to improve intestinal antibacterial defense and permeability as well as to reduce gut BT in CCl 4 -induced [110] and bile-duct-ligated cirrhotic rodents [111]. In addition, in two different cirrhotic animal models obeticholic acid has shown clear portal hypotensive action mediated by lowering intrahepatic vascular resistance [111,112].…”

Section: Potential Mechanisms Of Intestinal Barrier Dysfunction In CImentioning

confidence: 99%

Changes of Intestinal Functions in Liver Cirrhosis

2016

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Background: Understanding of the gut-liver axis is important for the up-to-date management of liver cirrhosis, and changes of intestinal functions form the core of this interesting research field. Summary: Most investigators noted small intestinal dysmotility in their patients with liver cirrhosis. Marked changes in the contraction pattern were observed in early manometric studies. The orocecal transit time, particularly small intestinal transit, has generally been reported to be prolonged, which has been demonstrated in multiple investigations to be related to the severity of the liver disease (e.g., Child-Pugh class), the presence of small intestinal bacterial overgrowth (SIBO) and hepatic encephalopathy (HE) as well as a history of spontaneous bacterial peritonitis. Bacteriologically proven SIBO in proximal jejunal aspiration has been reported to be present in up to 59% of cirrhotic patients and is associated with systemic endotoxemia. Clinical and experimental studies suggest that delayed small bowel transit in liver cirrhosis may lead to SIBO, which could contribute to the symptoms of abdominal pain and diarrhea. In addition to autonomic neuropathy, metabolic derangements and diabetic state, SIBO itself may delay intestinal transit in cirrhotic patients. Several studies, both from the West and the East, have shown that the gut microbiota is altered in cirrhotic patients and particularly those with HE. Further, a quantitative change in Bacteroides/Firmicutes ratio, with a prevalence of potentially pathogenic bacteria (e.g., Enterobacteriaceae) and reduction in specific commensals (e.g., Lachnospiraceae), has been described. Structural and functional changes in the intestinal mucosa that contribute to increases in intestinal permeability for bacteria and their products have been observed in patients with liver cirrhosis, which is considered as an important pathogenetic factor for several complications. The mechanism of intestinal barrier dysfunction in cirrhosis is multifactorial, including alcohol, portal hypertension (vascular congestion and dysregulation), endotoxemia, SIBO, local inflammation and, most likely, immunological factors and medications. Key Messages: This review summarizes major achievements regarding intestinal dysfunction in cirrhosis for future gastroenterology research. The question of whether this intestinal barrier dysfunction is accompanied and/or at least partly caused by structural and functional changes in the epithelial tight junction proteins is as yet unsolved. Development of new strategies to modulate gut-liver interaction is urgently needed.

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Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats

Cited by 152 publications

References 36 publications

Evolving insights in the pathophysiology of complications of cirrhosis: The farnesoid X receptor (FXR) to the rescue?

Evolving insights in the pathophysiology of complications of cirrhosis: The farnesoid X receptor (FXR) to the rescue?

Farnesoid X Receptor Agonist as a new treatment option for Non-Alcoholic Fatty Liver disease: A Review

Changes of Intestinal Functions in Liver Cirrhosis

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