Complications in Cirrhosis

Patients with cirrhosis are at high risk for dysbiosis due to pathological interactions between the liver and GI tract.2

Gut-Liver Interactions

Portal hypertension, alterations in gut microbiota, and inflammation can increase intestinal permeability and the risk for bacterial translocation.2,6

During disease progression, bile acid production in the liver and secretion into the intestine is suppressed due to inflammation caused by bacterial translocation and gut microbiota-derived metabolites. Decreased bile acid secretion into the intestine favors the overgrowth of pathogenic and proinflammatory microbiota, further perpetuating gut dysbiosis.2,3

Once cirrhosis develops, alterations in gut microbial composition and function progress to a point in which they contribute to cirrhotic complications.1

Changes Throughout Progression of CLD3

Examples of cirrhotic complications that may be related to gut microbial imbalance:

HE

HE is a common complication of cirrhosis characterized by cognitive impairment.6 Gut microbiota may contribute to the development of HE via the production of ammonia, a neurotoxin and inflammatory mediator.2 Gut microbial changes in patients with HE have been noted early on and throughout disease progression.1,4 Bacterial translocation across the gut epithelial barrier and SIBO also occur, contributing to endotoxemia and systemic inflammatory response that predispose patients to symptoms of covert and overt HE.2

SBP

Gut microbial activity plays an integral role in the development of SBP. An imbalance in gut microbiota may further predispose patients to this complication of liver disease.1 In patients with cirrhosis, bacterial overgrowth, increased intestinal permeability, and GI immune dysfunction allow bacteria to migrate to mesenteric lymph nodes and then to the systemic circulation, resulting in SBP.1,2 Studies show a high abundance of gram-negative bacteria of the Enterobacteriaceae family in ascitic fluid cultures, which is also highly abundant in the gut of patients with cirrhosis.1

ACLF

Patients with ACLF often have a significant imbalance in gut microbiota. This has been associated with a higher level of endotoxemia and an increase in gram-negative bacteremia on stool microbiome analysis. Gut microbial imbalance in patients with ACLF has also been identified as an independent predictor of mortality.1

progression of symptoms across liver health: healthy, compensated, decompensated, ACLF, post-transplant

Adapted, with permission, from: Acharya C, Bajaj JS. Altered microbiome in patients with cirrhosis and complications. Clin Gastroenterol Hepatol. 2019;17:307-321.

TARGETING GUT MICROBIOTA IN CLD
GI = gastrointestinal
CLD = chronic liver disease
HE = hepatic encephalopathy
SIBO = small intestinal bacterial overgrowth
SBP = spontaneous bacterial peritonitis
ACLF = acute-on-chronic liver failure
 
 

References

  1. Acharya C, Bajaj JS. Gut microbiota and complications of liver disease. Gastroenterol Clin North Am. 2017;46(1):155-169.
  2. Oikonomou T, Papatheodoridis GV, Samarkos M, Goulis I, Cholongitas E. Clinical impact of microbiome in patients with decompensated cirrhosis. World J Gastroenterol. 2018;24(34):3813-3820.
  3. Acharya C, Bajaj JS. Altered microbiome in patients with cirrhosis and complications. Clin Gastroenterol Hepatol. 2019;17:307-321.
  4. Bajaj JS, Heuman DM, Hylemon PB, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol. 2014;60(5):940-947.
  5. Minemura M, Shimizu Y. Gut microbiota and liver diseases. World J Gastroenterol. 2015;21(6):1691-1702.
  6. Boursier J, Mueller O, Barret M, et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology. 2016;63(3):764-775.
  7. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715-735.
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