NAFLD*: intestinal dysbiosis and risk of liver cancer

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Impairments of the intestinal microbiota are thought to contribute to the risk of developing hepatocellular carcinoma in patients suffering from metabolic steatopathy.

 

Is there a relationship between the composition of the intestinal microbiota and hepatocarcinogenesis? This question has been addressed by an Italian research team, through the characterization of the bacterial populations and inflammatory reactions in subjects with metabolic steatopathy. The team studied three groups: 20 patients with cirrhotic NAFLD, 21 patients with both cirrhotic NAFLD and hepatocellular carcinoma, and 20 healthy controls. Through blood and stool samples, the microbiotas, intestinal membrane permeability (presumed to be increased in cases of hepatic steatosis), the inflammatory state, and the status of circulating monocytes were characterized.

NAFLD and higher levels of inflammatory markers

As expected, all NAFLD patients displayed greater intestinal permeability, synonymous with increased penetration by microorganisms and their secretions. In addition, individuals suffering from liver cancer presented with a particularly high level of fecal calprotectin and plasma cytokines (the interleukins IL-8, IL-13 and the chemokines CCL3, CCL4, CCL5), as well as activation of circulating monocytes. All are markers of systemic inflammation.

Involvement of the gut-liver axis in carcinogenesis

Analysis of the bacteria of the fecal microbiota in NAFLD patients revealed an overabundance of Enterobacteriaceae and Streptococcus and low levels of Akkermansia. Patients suffering from hepatocellular carcinoma also displayed increased levels of Bacteroides and Ruminococcaceae, coupled with a reduction in Bifidobacterium. All these data enabled the researchers to conclude that the gut-liver axis was involved in hepatocarcinogenesis, and that intestinal inflammation was both correlated with humoral and cellular parameters of systemic inflammation and influenced by the composition of the local microbiota. This observation could lead to the improvement of primary and/or secondary management of hepatic carcinomas by acting on the bacterial populations: intestinal decontamination, administration of probiotics and prebiotics, fecal transplant, etc.

 

* NAFLD = Non Alcoholic Fatty Liver Disease. Disorder characterized by an excessive accumulation of fat in the liver, in the form of  triglycerides

 

Sources:

F. Romana Ponziani, S. Bhoori, C. Castelli, et al. Hepatocellular Carcinoma is Associated with Gut Microbiota Profile and Inflammation in Non-Alcoholic Fatty Liver Disease. doi: 10.1002/hep.30036.