CRC Biomarkers in the Microbiome?

There is an established link between colorectal cancer (CRC) and the human microbiome, so much so that certain bacteria have been seen to cause cancer in some mouse models (1). Despite this, there is limited understanding of the mechanisms behind the link – both in cancers and precancerous lesions.

Ranko Gacesa, a researcher at the University Medical Center Groningen (UMCG) in the Netherlands, wanted to help fill the knowledge gap (2). “We set out to test associations between the microbiome and both pre-existing lesions, as well as development of new lesions – ones that developed between one and five years after we sampled microbiota,” says Gacesa.”

The research used data from the Dutch Microbiome Project Cohort, which was created to establish what constitutes a standard “healthy” gut, using data for more than 8200 participants pulled from labs across the country (3).

“We identified that both pre-existing and future lesions are associated with the gut microbiome,” Gacesa explains. “The pre-existing pathologies – especially CRC – were linked to reduced microbiome diversity, a decrease in beneficial commensals such as butyrate-producing Faecalibacterium, and an increase in pathobionts, including bacteria previously shown to cause cancer in mice.” 

Gacesa also notes that new associations were also found between the microbiome and pre-cancerous lesions. According to Gacesa, these were similar to those found in cancer, albeit with a lower effect size – implying that changes in the gut microbiome are caused by cancerous and precancerous pathologies.

“One interesting result was identified in Alistipes finegoldii – a bacteria previously shown to cause cancer in mouse models,” says Gacesa. The team observed that the bacteria were more abundant in individuals who had colorectal cancer within the last five years. “Interestingly, it shows no difference versus healthy controls in individuals who had pre-cancerous polyps or who developed polyps or cancer in the future… At this point, we do not know why this is the case, but it makes for an interesting target for future research.”

Could the gut microbiome be used as a biomarker for colorectal cancer risk – and perhaps eventually other diseases? “Considering the gut microbiome is linked to cancer development in the future, it implies we could use the microbiome to identify individuals at risk for development of CRC – and, in theory, try and change the microbiome to reduce this risk, possibly by changing diet or using probiotics,” answers Gacesa, while noting that their findings are based only on one study in one population. Validation in independent data and cohorts is required, he says, which may not be straightforward: “One of the major difficulties with microbiome biomarkers is that it would require very strict standardization of sample collection, processing, and testing methods to ensure consistency.”

Finally, Gaseca emphasizes the collaborative nature of the research: “I would like to thank all the colleagues from UMCG and the newly opened Groningen Microbiome Hub as well as Lifelines biobank and all the participants in the Dutch Microbiome Project who made this study possible.”