Colorectal cancer ‘signature’ transcends culture and diet

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Patients with colorectal cancer have the same consistent changes in their gut bacteria across continents, cultures, and diets, according to a new study.

Scientists hope to one day use the findings to develop a new method of diagnosing the disease.

Researchers have long known that cancers arise due to environmental exposures such as unhealthy diet or smoking. Lately, the microbes living in and on our bodies have entered the stage as key players.

But the role that gut microbes play in the development of colorectal cancer—the third most common cancer worldwide—remains unclear. To determine their influence, association studies have aimed to map how the microbes colonizing the gut of colorectal cancer patients differ from those of healthy people.

Now, researchers have analyzed multiple existing microbiome association studies of colorectal cancer together with newly generated data.

Disease ‘signature’

“During disease our microbiome may change,” says Manimozhiyan Arumugam, associate professor at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen. “If these changes are consistent in each person getting the same disease then it is a signature of disease.

“What we show in our study is that the gut microbiome signatures in colorectal cancer seem to be universal. This is despite geography, culture, and lifestyle. In the future we hope we can use these signatures as biomarkers and as a diagnostic tool for colorectal cancer.”

For the study, which appears in Nature Medicine, researchers analyzed and used data from seven cohorts from China, Austria, France, Germany, the US, Italy, and Japan.

“We used a rigorous machine learning analysis to identify microbial signatures for colorectal cancer. We validated these signatures in early cancer stages and in multiple studies, so they can serve as the basis for future non-invasive cancer screening,” says Georg Zeller from the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany.

Bile acids and choline

The study focuses on a process in which certain gut bacteria turn bile acids (part of our digestive juices) into metabolites that can be carcinogenic.

A related study from the University of Trento shows how certain classes of bacteria degrade choline, an essential nutrient contained in meat and other foods, and turn it into a potentially dangerous metabolite. Earlier studies show this metabolite increases cardiovascular disease risk, and the new study now also links it to colorectal cancer.

One of the challenges of metagenomic studies, which are based on genetic material from microbes in environmental samples such as stool, is to link genetic fragments to the various microbial organisms they belong to. The goal of this so-called taxonomic profiling task is to identify and quantify the bacterial species present in the sample.

“Despite different approaches in taxonomic profiling and statistical analysis, our studies reached very similar conclusions, which makes this one of the most promising cases for microbiome-based diagnostics so far,” says EMBL group leader Peer Bork.

Microbiome samples

Scientists have yet to establish the role of gut microbes in colorectal cancer. If the changes in the microbiome play a role in developing the cancer, they could also be a therapeutic target.

Therefore, Arumugam hopes for more focus on the role of microbiome in diseases and that researchers will recognize the advantages of collecting microbiome samples, for example, in large cohorts.

“In Denmark, we have large biobanks with precious samples from human volunteers and, more importantly, an abundance of health-related information from the national health registries. Given our unique advantage, prioritizing to add microbiome samples to these biobanks will make a major impact in identifying the role of microbiome in diseases,” says Arumugam.

EMBL, DKFZ, the Huntsman Cancer Foundation, the Intramural Research Program of the National Cancer Institute, ETH Zürich, the European Research Council, the Novo Nordisk Foundation, the Danish Diabetes Academy, and the Matthias-Lackas Foundation funded the work.

Bork, Zeller, and two other coauthors have patented a method for diagnosing colorectal cancer based on analyzing the gut microbiome.

Source: University of Copenhagen