(Photo: University of Leeds)

Gut microbiota has wide reaching effects on health and disease. A study published in Proceedings of the National Academy of Sciences, PNAS, has demonstrated that gut imbalance promotes the onset of colorectal cancer, going on to invent a blood test to identify the epigenetic signatures.

Sporadic Colorectal Cancer is one of the most common cancers worldwide with over 42,000 cases a year in the UK and a 57% survival rate over ten years. The exact causes of colorectal cancer are unknown, but diet has been strongly implicated.

Gut microbiota were investigated as a potential link between diet, environmental stresses, and colon cells. Cancer cells are known to have an increased number of mutations not only to the DNA but also to the epigenome. Epigenetic marks affect gene expression without altering the underlying DNA, such as DNA methylation.

The study investigated the gut microbiota by transplanting faecal microbiota from patients with colorectal cancer into germ-free mice. The mice developed lesions and altered levels of DNA methylation after the transplant. An increased amount of DNA methylation has been previously linked to colonic lesions. Analysing the genes in the mice and colorectal cancer tissues revealed 8 genes that were significantly hypermethylated versus controls. Three of these genes were used to generate a representative test – the Cumulative Methylation Index (CMI).

A blood test was developed from the CMI and corroborated on 1,000 asymptomatic patients who were due to have a colonoscopy. Using the CMI, 35 % of asymptomatic individuals were shown to have early signs of colorectal cancer versus the 4% patients identified with a colonoscopy alone. The CMI was deemed a predictive factor of colorectal cancer.

In addition, the bacteria present in those with a higher CMI were identified via whole metagenomic analysis. This revealed a host of changes in the proportion of bacterial species, potentially providing another test for early diagnosis of colorectal cancer. 

Microbiota are an important avenue for research as diet has been implicated more and more in disease and metabolism. Faecal transplants are already used as an effective treatment for Clostridioides difficile infections and may help children with autism. This study opens up an exciting avenue for cancer treatment and how the gut microbiota could be altered for our benefit.