An international group of researchers has found a link between gut bacteria in the bile duct and a raised risk of developing bile duct cancer. The team hopes the finding will lead to new, more targeted therapies for the rare and aggressive disease.

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The researchers profiled the microbiomes of fluke-associated (Ova) versus non-associated (non-Ova) tumor (T) and normal (N) bile duct tissues, and found differences in relative proportions of bacteria species.
Image credit: Genome Institute of Singapore

The team, including researchers from Khon Kaen University in Thailand and the Genome Institute of Singapore, reports the discovery in the journal EBioMedicine.

It is a well-established fact that disease arises from interactions between our cells and our environment.

However, what is becoming increasingly clear is that a significant amount of this cell-environment interaction occurs inside the body, where cells interact with our microbiome – the trillions of bacteria that live inside us.

One of the study’s senior and corresponding authors, Dr. Niranjan Nagarajan, who heads a group developing statistical and computing tools for analyzing the human microbiome at the Genome Institute of Singapore, says:

“Until recently, our understanding of bacterial communities resident in our body and their association with diseases has been limited.”

While their role in the development of colon and gastrointestinal cancers is now better understood, this cannot be said of the involvement of bacteria in the development of bile duct cancer, note the authors.

Bile duct cancer, or cholangiocarcinoma, is cancer that starts in the bile duct, a series of thin tubes that transports bile from the liver and gallbladder to the small intestine to help digest fats in food.

Bile duct cancer is not common. In the United States, about 2,000-3,000 people develop it each year. The risk of developing the cancer is linked to presence of cysts and inflammations that block the bile duct.

The cancer is more common in Southeast Asia because infection by the liver fluke parasite – which causes chronic inflammation of the bile duct – is much more common there.

Because symptoms often do not present in the early stages of bile duct cancer, most people are not diagnosed with the disease until it is advanced, making it much harder to treat successfully. Thus, the 5-year survival prognosis is much less optimistic than for many cancers, ranging from 5-30 percent, depending on the type of bile duct cancer.

Our digestive system is home to trillions of microbes – collectively known as the gut microbiome – without which it could not digest food, defend against disease, and even send signals to brain that affect mood and behavior.

As we learn about the gut microbiome, we are discovering that imbalances among the types of bacteria are linked to higher risk for diseases of the gut, including cancer.

The researchers wanted to find out whether this might be true of the bile duct as it is for other parts of the digestive system.

For their study, Dr. Nagarajan and colleagues profiled the bile duct microbiomes of bile duct cancer tissue sampled from liver fluke-infected and non-infected people.

The team found that compared with healthy tissue, cancerous bile duct tissue from non-fluke-infected patients had different proportions of bacteria species, the most significant being higher numbers of a species called Stenotrophomonas.

Also, compared with non-fluke-infected bile duct cancer tissue, fluke-infected cancer tissue contained gut bacteria whose metabolic outputs (bile acids and ammonia) have been previously linked to the formation of cancer.

The authors note that when taken together, the results show “how the unique microbial communities resident in the bile duct, parasitic infections and the tissue microenvironment can influence each other, and contribute to cancer.”

Although the research is still in its early stages, the team believes the findings will pave the way for new therapies to treat bile duct cancer by addressing the microbiome, something that is easier to manipulate than the genome.

The associations detected in this study provide a smoking gun for the role of bacteria in bile duct cancer, and we hope that this discovery will accelerate our search for a cure for cholangiocarcinoma.”

Dr. Niranjan Nagarajan

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