Diets low in carbohydrates and soluble fibres can drive the growth of polyps in the colon, increasing the risk of developing colorectal cancer, according to University of Toronto researchers.
In a study published in the journal Nature Microbiology , scientists examined the effects of three diets - normal, low-carb and Western-style (high-fat and high-sugar) - on colorectal cancer development.
They found that a unique strain of E. coli bacteria, when paired with a diet low in carbs and soluble fibre, drives the growth of polyps in the colon, which can be a precursor to cancer.
"Colorectal cancer has always been thought of as being caused by a number of different factors including diet, gut microbiome, environment and genetics," says senior author Alberto Martin, a professor and Sanofi Pasteur Chair in Human Immunology in the Temerty Faculty of Medicine.
"Our question was, does diet influence the ability of specific bacteria to cause cancer?"
To answer this question, the researchers, led by postdoctoral researcher Bhupesh Thakur, conducted preclinical studies using the three diets and models that had been colonized with one of three bacterial species previously linked to colorectal cancer.
Only one combination - a low-carb diet paired with a strain of E. coli that produces the DNA-damaging compound colibactin - led to the development of colorectal cancer.
The researchers also found that a diet deficient in fibre increased inflammation in the gut and altered the community of microbes that typically reside there, creating an environment that allowed the colibactin-producing E. coli to thrive.
Additionally, low-carb diets were associated with a thinner layer of mucus separating the gut microbes from the colon epithelial cells. The mucus layer acts as a protective shield between bacteria in the gut and the cells underneath, so with a weakened barrier, more colibactin could reach colon cells and drive tumour growth.
These effects were especially strong in subjects with genetic mutations in the mismatch repair pathway that hindered their ability to fix damaged DNA.
Defects in DNA mismatch repair are frequently found in colorectal cancer - the fourth most commonly diagnosed cancer in Canada. An estimated 15 per cent of these tumours have mutations in mismatch repair genes. These mutations also underlie Lynch syndrome, a genetic condition that significantly increases a person's risk of developing certain cancers, including colorectal cancer.
The findings suggest that avoiding a low-carb diet - or taking specific antibiotics to get rid of colibactin-producing bacteria - could reduce the risk of colorectal cancer among Lynch syndrome patients harbouring colibactin-producing microbes, says Martin.
He points out that a particular strain of E. coli called Nissle, which is commonly found in probiotics, also produces colibactin. His lab is now exploring whether long-term use of the probiotic is safe for people with Lynch syndrome or those who are on a low-carb diet.
The study also showed that adding soluble fibre to a low-carb diet resulted in lower levels of the cancer-causing E. coli, fewer tumours and less DNA damage.
"We supplemented fibre and saw that it reduced the effects of the low-carb diet," Thakur says. "Now we are trying to find out which fibre sources are more beneficial, and which are less beneficial."
To do this, Thakur and Martin are teaming up with the University of Alberta's Heather Armstrong to test whether supplementation with a soluble fibre called inulin can reduce colibactin-producing E. coli and improve gut health in high-risk individuals, including people with inflammatory bowel disease.
"Our study highlights the potential dangers associated with long-term use of a low-carb, low-fibre diet, which is a common weight-reducing diet," says Martin. "More work is needed but we hope that it at least raises awareness."
This research was funded by the Canadian Institutes of Health Research.
