Low-Carb Diets May Fuel Colorectal Cancer, Concerning New Study Reveals

A low-carb diet can worsen the cancer-causing effects of certain gut bacteria by weakening the gut barrier and altering the microbiome. This increases colorectal cancer risk, especially in individuals with genetic mutations affecting DNA repair. However, soluble fiber may help counteract these effects.

Researchers at the University of Toronto have demonstrated that a low-carbohydrate diet can amplify the DNA-damaging effects of certain gut microbes, increasing the risk of colorectal cancer.

The study, published in Nature Microbiology, examined how three different diets—normal, low-carbohydrate, and Western-style (high in fat and sugar)—interacted with specific gut bacteria to influence colorectal cancer development in mice.

The findings revealed that a particular strain of E. coli, when combined with a diet low in carbohydrates and soluble fiber, promotes the growth of polyps in the colon, a potential 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 of immunology at U of T’s Temerty Faculty of Medicine.

“Our question was, does diet influence the ability of specific bacteria to cause cancer?”

How a Low-Carb Diet Increases Cancer Risk

To answer this question, the researchers, led by postdoctoral fellow Bhupesh Thakur, examined mice that were colonized with one of three bacterial species that had been previously linked to colorectal cancer and fed either a normal, low-carb, or Western-style diet.

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 found that a diet deficient in fiber 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.

They also showed that the mice fed a low-carb diet had a thinner layer of mucus separating the gut microbes from the colon epithelial cells. The mucus layer acts as a protective shield between the bacteria in the gut and the cells underneath. With a weakened barrier, more colibactin could reach the colon cells to cause genetic damage and drive tumor growth. These effects were especially strong in mice with genetic mutations in the mismatch repair pathway that hindered their ability to fix damaged DNA.

While both Thakur and Martin emphasize the need to confirm these findings in humans, they are also excited about the numerous ways in which their research can be applied to prevent cancer.

Defects in DNA mismatch repair are frequently found in colorectal cancer, which is the fourth most commonly diagnosed cancer in Canada. An estimated 15 percent of these tumors have mutations in mismatch repair genes. Mutations in these genes also underlie Lynch syndrome, a genetic condition that significantly increases a person’s risk of developing certain cancers, including colorectal cancer.

“Can we identify which Lynch syndrome patients harbor these colibactin-producing microbes?” asks Martin. He notes that for these individuals, their findings suggest that avoiding a low-carb diet or taking a specific antibiotic treatment to get rid of the colibactin-producing bacteria could help reduce their risk of colorectal cancer.

Probiotics and Dietary Modifications

Martin points out that a strain of E. coli called Nissle, which is commonly found in probiotics, also produces colibactin. Ongoing work in his lab is exploring whether long-term use of this probiotic is safe for people with Lynch syndrome or those who are on a low-carb diet.

Thakur is keen to follow up on an interesting result from their study showing that the addition of soluble fiber to the low-carb diet led to lower levels of the cancer-causing E. coli, less DNA damage, and fewer tumors.

“We supplemented fiber and saw that it reduced the effects of the low-carb diet,” he 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 Heather Armstrong, a researcher at the University of Alberta, to test whether supplementation with a soluble fiber called inulin can reduce colibactin-producing E. coli and improve gut health in high-risk individuals, like people with inflammatory bowel disease.

“Our study highlights the potential dangers associated with long-term use of a low-carb, low-fiber diet, which is a common weight-reducing diet,” says Martin.

“More work is needed but we hope that it at least raises awareness.”

Reference: “Dietary fibre counters the oncogenic potential of colibactin-producing Escherichia coli in colorectal cancer” by Bhupesh Kumar Thakur, Yann Malaise, Saurav Roy Choudhury, Anna Neustaeter, Williams Turpin, Catherine Streutker, Julia Copeland, Erin O. Y. Wong, William W. Navarre, David S. Guttman, Christian Jobin, Kenneth Croitoru and Alberto Martin, 3 March 2025, Nature Microbiology.
DOI: 10.1038/s41564-025-01938-4

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