Global microbial signatures for colorectal cancer

Cancers have long been known to arise due to environmental exposures such as unhealthy diet or smoking. Lately, the microbes living in and on our body 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 — is unclear. To determine their influence, association studies have aimed to map how the microbes colonizing the gut of colorectal cancer patients are different from those that inhabit healthy subjects.

Now, researchers from University of Copenhagen, EMBL, the University of Trento, and their international collaborators have analysed multiple existing microbiome association studies of colorectal cancer together with newly generated data. Their meta-analyses establish disease-specific microbiome changes, which are globally robust — consistent across seven countries on three continents — despite differences in environment, diet and life style.

“During disease our microbiome may change. 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 life style. In the future we hope we can use these signatures as biomarkers and as a diagnostic tool for colorectal cancer,” says Manimozhiyan Arumugam, Associate Professor at the Novo Nordisk Foundation Center for Basic Metabolic Research.

The new research results have been published in the scientific journal Nature Medicine. It is the first time a meta-analyses for colorectal cancer has been done on this scale. In the study, the researchers have analyzed and used data from seven cohorts from the countries 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,” explains Georg Zeller from the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany.

Two studies same conclusion

The study led by UCPH and EMBL scientists focuses on a process in which certain gut bacteria turn bile acids that are 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. This metabolite has previously been shown to increase cardiovascular disease risk, and can now also be linked 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.

The role of gut microbes in colorectal cancer still needs to be established. If the changes in the microbiome play a role in developing the cancer, they could also be a therapeutic target. Therefore, Manimozhiyan Arumugam hopes that there will be 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 Manimozhiyan Arumugam.