The intestinal microbiota could be used for early detection of hepatocellular carcinoma

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Specific alterations of the intestinal microbiota could be warning signs of hepatocellular carcinoma. New early diagnosis tools might be derived from this finding to improve the prognosis of this type of cancer, which is among the deadliest ones.

 

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death in the world. It is diagnosed late in most cases, once signs of impaired hepatic function become visible (jaundice, ascites) in the context of hepatitis B or C, alcoholism, or non-alcoholic steatohepatitis (NASH). A Chinese team tried to determine whether specific changes within the intestinal microbiota reflected the transition from cirrhosis to early cancer, in order to expedite diagnosis and treatment. Recent discoveries revealed the existence of a gut-liver axis involved in the correlation between alterations of intestinal microbiota and liver inflammatory process.

Activation of the tumoral process

The researchers first analyzed stool samples from 40 subjects with cirrhosis, 75 patients with early HCC, and 75 healthy individuals, all enrolled from different regions of China (East, Center, North‑West). Cirrhosis has been proven to be associated with a decreased bacterial abundance and diversity compared to that of control subjects. On the contrary, the intestinal microbiota of patients with early HCC was significantly more diversified and more abundant than that of cirrhotic patients: decrease in butyrate-producing bacteria (butyrate is a short-chain fatty acid contributing to the integrity of the intestinal mucosa) such as Coprococcus, Ruminococcus, Faecalibacterium; increase in proinflammatory lipopolysaccharides(LPS)-producing bacteria such as Klebsiella and Haemophilus; decrease in Akkermansia muciniphila that promotes the production of intestinal mucosa. All these events suggest that the cancerous process is triggered through the gut-liver axis, and thus indicate the shift from cirrhosis to early HCC.

A robust diagnostic model

More detailed statistical analyses revealed 30 operational taxonomic units (OTU)* that the team used to build a diagnostic model which was then tested in a second phase including 56 control subjects, 30 patients with early HCC and 45 patients with advanced HCC, as well as 18 patients from Xinjiang (North-West) and 80 from Zhengzhou (Center). The trial was a success: the model was validated, and further confirmed by the multicenter nature of this cohort. These results still need to be assessed in different populations to confirm the potential of the intestinal microbiota as a non-invasive diagnostic tool for early detection of HCC. This avenue is already being explored for other conditions such as pancreatic carcinoma, liver transplant, as well as type 2 diabetes mellitus and colorectal cancer.

 

*OTU refers to bacterial “species” that are phylogenetically very close

 

Sources:

Z Ren et al, Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma, Gut, 25 July 2018