The bile duct, which carries digestive fluids from the liver, through the gall bladder to the small intestines, has a unique community of resident bacteria that contribute to cancer.
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From the stomach, to the gut, and the breast — scientists have shown a link between cancer and the microbial communities living in various organs of our body. Now, researchers at A*STAR have made a new association between the microbes in the bile duct and fatal tumor formation.
“We don’t fully understand the risk factors or environmental causes for many cancers,” says Niranjan Nagarajan at the A*STAR Genome Institute of Singapore, who led the study. “Microbiome research allows us to figure out whether these cancers might have a microbial basis, and potentially intervene to prevent or reduce the risk.”
Bile duct cancer, or cholangiocarcinoma, affects only about one in every hundred thousand individuals worldwide, but incidence and mortality rates have increased in Southeast Asia and in Thailand they are as high as 85 in 100,000. A major risk factor associated with cholangiocarcinoma in the region is infection from the liver fluke parasite found in raw fish.
Nagarajan and colleagues wanted to know if the little studied bile duct microbiome also contributed to the disease. Using a technique known as 16S rRNA sequencing, they studied the bacterial composition in samples of healthy bile duct tissue and adjacent tumors taken from 60 patients, including those who had been infected with liver flukes.
Overall, they found that the bile duct microbiome was dominated by exotic species not typically seen in the human body. “The diversity was remarkable,” says Nagarajan. “Bile duct tissue has a unique microbial signature even compared to nearby organs like the liver.”
Comparative analyses presented more surprises. In samples not infected with liver fluke, tumor tissue had significantly higher levels of Stenotrophomonas bacteria. Several Stenotrophomonas species are known to trigger inflammation, which is a common mechanism by which bacteria cause cancer.
The researchers could not, however, clearly distinguish between normal and tumor tissue in liver-fluke-infected samples. But they did notice that, compared to the parasite-free subset, the infected samples had an abundance of intestinal Bifidobacteriaceae, Enterobacteriaceae and Enterococcaceae. Further computational analysis revealed that these bacteria metabolize ammonia and bile acids, which are known to promote colorectal cancer.
The researchers plan to conduct further genomic analyses on a much larger sample size and study these processes in cell culture experiments. “We want to grow human bile duct cell lines, expose them to the various bacteria and see how they respond,” says Nagarajan. “Even if it does not lead to the initiation of the cancer, bacteria could be accelerating the process of tumor formation.”
The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore. For more information about the team’s research, please visit the Nagarajan Lab webpage.
