Cancer risk is shaped by a complex interplay of genetics, environment, age and microbial composition in the gut. While some factors like inherited genetic mutations are out of our control, dietary habits remain a powerful and modifiable influence.
Mounting evidence suggests that what we eat not only shapes the composition of our gut microbiota but also plays a critical role in cancer susceptibility, particularly in colorectal cancer (CRC).
In this third installment of our miniseries, we explore the contrasting roles of harmful and protective dietary components – such as the Western diet and red meat versus dietary fiber and polyphenols – on gut health and cancer development.
The Western diet
The Western diet – also known as the Standard American Diet – is marked by high consumption of red and processed meats, refined sugars, saturated fats and ultra-processed foods (UPFs), while lacking in whole grains, fruits, vegetables and dietary fiber. This nutritional imbalance has been linked to obesity, chronic inflammation and disruptions in the gut microbiome – all factors associated with increased risk for cancers, such as CRC.
UPFs – including soft drinks, packaged snacks, ready-to-eat meals and sugary cereals – are also of concern. Their widespread appeal stems from their long shelf life, affordability and convenience, which has led to their pervasive presence in high-income countries. For example, UPFs contribute to 29.1% of total daily energy intake in France, 42% in Australia and 57.9% in the US. This dietary shift toward hyperpalatable, energy-dense foods is now recognized as a major public health concern.
Mechanistic studies have shown that diets rich in saturated fats and cholesterol can reprogram the gut microbiome and promote a pro-inflammatory immune state. In animal models, high-fat diets – especially those based on animal fats such as lard – have been found to create favorable conditions for cancer metastasis by altering immune cell populations and enriching gut bacteria with tumor-promoting potential, such as Clostridium sordellii and Desulfovibrio vulgaris.
While official dietary guidelines are relatively recent, growing evidence links high cholesterol consumption – often accompanied by saturated fat in red meat and processed foods – to chronic diseases, including cancer. In one study, mice fed a high-fat, high-cholesterol diet developed spontaneous fatty liver disease and liver cancer, alongside a loss of beneficial gut microbes such as Bifidobacterium and Bacteroides, which are typically depleted in individuals with elevated blood cholesterol and liver malignancies.
“There is also good evidence that specific foods are associated with cancer risk,” said Dr. Emily Vogtmann, Earl Stadtman Investigator at the National Cancer Institute. However, she cautioned that “the relationship between the gut microbiome and cancer, or how the gut microbiome may mediate associations between diet and cancer, is less well understood.”
Much of the existing evidence comes from animal studies, while human studies are often cross-sectional, making it difficult to determine whether observed microbiome changes are a cause or consequence of cancer. “We need good data from prospective studies where dietary data and gut microbiome samples are collected before people develop cancer to really start to understand the complex relationship between diet, the gut microbiome and cancer,” Vogtmann added.
In 2015, the World Health Organization’s International Agency for Research on Cancer classified red and processed meats as probable human carcinogens (Group 2A), associating their consumption with an increased risk of CRC. Research shows that each additional 50 g/day of red or processed meat increases CRC risk by 16%, rising to 22% at 100 g/day. Such diets have been shown to disrupt gut microbial communities, enriching bacteria like Bacteroides, Bilophila and Alistipes, which are linked to inflammation, mucosal damage and the production of carcinogenic compounds.
Conversely, diets high in plant-based foods and fiber tend to support a more favorable gut microbiome. Populations with such dietary patterns exhibit higher levels of beneficial bacteria like Bifidobacterium, Roseburia and Faecalibacterium prausnitzii, which produce short-chain fatty acids (SCFAs) such as butyrate. These metabolites are known to maintain intestinal barrier integrity and suppress tumor formation.
Still, Vogtmann urges caution in overinterpreting what constitutes a “healthy” or “dysbiotic” microbiome: “I would argue that we do not know what gut dysbiosis is, since that would require understanding what represents a healthy gut microbiome.” Given the large variability between individuals – and even across global populations – defining a universal healthy microbiome remains elusive. “There may be overall gut microbiome changes due to a Western diet or other unhealthy exposure, but it would be hard to say that this is driving gut dysbiosis,” she added.
Protective dietary components: Fiber and polyphenols
While some foods can disrupt gut microbial balance and contribute to cancer development, others may offer protection by nurturing a healthier microbiome.
A Mediterranean-style diet – rich in fruits, vegetables, whole grains and lean proteins such as fish – has been shown to reduce inflammation and protect against chronic diseases, including cancer. A meta-analysis highlighted that gastrointestinal disorders and cancer are closely linked to both dietary habits and gut inflammation. The gut microbiota of individuals following a Mediterranean diet is typically enriched with beneficial, anti-inflammatory bacteria such as Akkermansia, alongside a reduction in Fusobacterium, a pathogenic species associated with malignancy.
Still, the current body of evidence surrounding the positive impact of the Mediterranean-style diet on gut health has limitations. “Unfortunately, few prospective cohort studies have collected fecal samples, and the majority of these samples were collected within the past few years,” said Vogtmann. “So, it would be hard to conclude that specific microbial signatures are protective against cancer, given the current data.”
Clinical and preclinical studies support that increasing dietary fiber promotes the growth of SCFA-producing bacteria and reduces inflammation in conditions like ulcerative colitis – a known risk factor for CRC. SCFAs also strengthen the intestinal barrier, regulate gene expression through histone deacetylase inhibition and trigger apoptosis in abnormal or pre-cancerous cells. However, not all respond equally to high-fiber diets, especially those with insufficient populations of fiber-fermenting microbes. This underscores the importance of personalized dietary strategies tailored to an individual’s microbiome composition.
Polyphenols – bioactive compounds found in fruits, vegetables, tea, coffee and nuts – also exhibit notable anti-cancer properties. These compounds are poorly absorbed in the upper gastrointestinal tract but are metabolized by gut microbes into smaller, active metabolites. These metabolites have been shown to suppress cancer cell proliferation, reduce oxidative stress and inflammation and enhance gut epithelial barrier function. Moreover, polyphenol intake has been associated with increases in probiotic bacteria, such as Lactobacillus and Bifidobacterium, and decreases in pro-inflammatory and pathogenic species.
“Increased intakes of fiber and polyphenol-rich foods (e.g., fruits and vegetables) have been observed to be associated with decreased risks of various cancers, such as CRC,” Vogtmann explained. “Fiber intake in particular has also been found to be related to increased gut microbial diversity, increased production of SCFAs and potentially decreased gut permeability. Increased gut microbial diversity is generally considered to be a marker of good health.”
“It is possible that at least some of the observed associations between fiber intake with cancer risk may be through changes to the gut microbiome, but more studies are needed to thoroughly investigate this hypothesis,” she added.
Challenges and misconceptions
A major source of confusion in the field of diet, gut health and cancer prevention lie in how risk is understood. As Vogtmann explained: “One point of confusion is related to individual versus population risk.”
Research often focuses on population-level effects, identifying trends that can inform public health guidelines. However, this does not always translate neatly to individual outcomes.
“Within the population, eating a healthy diet can decrease risk of cancer,” Vogtmann noted. “But at the individual level, a person who eats an extremely healthy diet could still develop cancer, or conversely, a person eating a very unhealthy diet may never develop cancer.” This highlights the complexity of disease risk and the importance of looking beyond diet alone.
“Really, diet is only a part of cancer prevention. Not smoking cigarettes (or quitting smoking if already a smoker), decreasing or eliminating alcohol intake, increasing physical activity and many other behaviors are important for cancer prevention,” explained Vogtmann.
Another challenge lies in translating emerging science into actionable advice. “For now, much of the diet-microbiome-cancer actionable advice is predominantly just the established diet-cancer advice,” said Vogtmann.
Despite growing public interest in gut health, longstanding barriers to healthy eating persist. “At least in the US, it has been hard to motivate the general population to consume a healthier diet due to a multitude of factors,” she said. However, Vogtmann spoke of the hope of “novel behavioral interventions, new drugs for weight loss and perhaps the incorporation of microbiome data may help motivate individuals to eat healthier diets.”