The presence of families Ruminococcaceae and genus Porphyromonadaceae in the gut microbiome might decrease the risk of primary liver cancers such as cholangiocarcinoma (CCA) and hepatocellular carcinoma, according to a recently published study in Liver International.

The incidence of CCA has steadily risen in the last 2 decades because, in most cases, diagnosis occurs at advanced stages, and the mortality associated with the disease is quite high, thus creating a real necessity for effective preventive measures that could decrease CCA incidence.

The fact that the gut microbiome plays an important role in human health and homeostasis is now widely accepted. There is abundant evidence that suggests that the human microbiome is linked to a great variety of diseases, such as diabetes, neurological diseases, obesity, and autoimmune diseases, among others. 

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Although some observational studies suggest a link between gut microbiome alterations and primary liver cancer, reverse causality, as well as potential confounding factors, it is difficult to confirm the correlation. 

Therefore, the authors aimed to assess the causality between primary liver cancer and gut microbiome alterations through a 2 sample Mendelian randomization (MR) method. The relationship was further validated by data sequencing from a case-control study.

“MR uses summary statistics from genome-wide association studies (GWAS) of large amounts of genetic variation to extract single nucleotide polymorphisms associated with exposure and outcome variables, further revealing clear causal relationships between the exposure and outcome,” the authors wrote.

In the studies, MR was based using data from GWAS dealing with the gut microbiome, CCA, and hepatocellular carcinoma.

The case-control study included 280 patients from the department of hepatobiliary surgery at the First Affiliated Hospital of Wenzhou Medical University, China. The genomic DNA of the gut microbiome of each patient was extracted from frozen stool samples. The comparison between bacteria from patients with liver cancer and healthy controls was performed using the Mann-Whitney test.

Results showed that the family Ruminococcaceae and genus Porphyromonadaceae were more abundant among healthy controls than in patients with hepatocellular carcinoma, suggesting that these microbiomes could be associated with less risk for hepatocellular carcinoma. On the other side, the family Porphyromonadaceae and genus Bacteroidetes appeared to reduce the risk for CCA.

“These gut microbes could be potential for hepatocellular carcinoma and ICC prevention and treatment,” the study team wrote. “At the same time, the bi-directional causal relationship between gut microbes and liver cancer requires higher quality GWAS data, and further investigations into the underlying mechanisms are necessary.”


Ma J, Li J, Jin C, et al. Association of gut microbiome and primary liver cancer: a two‐sample mendelian randomization and case‐control study. Liver Int. Published online October 27, 2022. doi:10.1111/liv.15466