High-Fat Diet Promotes Deadly Colon Cancer

Research has shown that the level of an oral and gut bacteria called F nucleatum increases when people switch from a low-fat, high-fiber diet to a diet high in fat and low in fiber-rich plant foods. Higher levels of F nucleatum are also a marker for a shorter life expectancy due to not only more cardiovascular related deaths but also more cancer deaths. A study that followed health professionals for several years found those with colon cancers positive for F nucleatum were more likely to have aggressive cancers. To determine if higher levels of the bacteria F nucleatum might be promoting colon cancer deaths, researchers conducted a prospective cohort study of 137,217 health professionals. During the follow-up period, they observed 1,019 cases of colorectal cancer. Of these 1,019 cases, 125 were F nucleatum-positive and 894 were F nucleatum-negative. “Prudent” diets of low-fat, high-fiber foods were associated with a reduced the risk of F nucleatum-positive but not the more benign F nucleatum negative colorectal cancers. This is important because the F. nucleatum-positive colon cancers grow faster, spread more rapidly, and are far deadlier than the F. nucleatum-negative tumors (1). Modern Western Diet Promotes Deadly Colon CancersAnother study also showed increased risk of deadly colon cancers in those who consumed a Western-style diet with a high amount of red and processed meats. The inflammatory effects of diets were estimated based on the empirical dietary inflammatory pattern (EDIP) score. The EDIP score is calculated based on the sum of weighted intake scores of 18 foods (processed meat, red meat, organ meat, fish, vegetables other than green leafy vegetables and dark yellow vegetables, refined grains, high-energy beverages, low-energy beverages, tomatoes, beer, wine, tea, coffee, snack foods, fruit juice, and pizza). These 18 food groups were selected based on their effects on inflammatory substances. Red meats and processed meats increased inflammation whereas tea, coffee, and vegetable intake were associated with lower levels of inflammatory substances. Higher plasma levels of interleukin 6, C-reactive protein, and tumor necrosis factor–receptor superfamily member 1B, (TNFRSF1B) are associated with more CVD and greater risk of at least some aggressive cancers. Higher EDIP scores indicate more inflammatory diets and lower scores indicate anti-inflammatory diets. Subjects were categorized into tertiles using cohort-specific cut-off points of the cumulative average EDIP scores. Information on lifestyles and medication was assessed using biennial questionnaires. Another study reported that during 28 years of follow up, of 124,433 participants, Dr. Liu and colleagues found 951 incident cases of colorectal carcinoma with tissue containing F nucleatum (2). The results of these studies increase our understanding of how diet impacts intestinal inflammation, at least in part by altering the gut’s microbiota, and in this case likely contribute to more aggressive colon cancers. More knowledge about diet and the microbiome, should enable us to develop healthier diet strategies to help prevent and possibly treat more deadly colorectal carcinomas.New Study Adds to How Gut Microbe Makes Cancers More Deadly The findings of a new study by Columbia University professor Yiping Han adds to our understanding of how diet and F. nucleatum appears to lead to more aggressive and deadly colon cancers. It also helps explain why some cases of colon cancer advance far more quickly than others, thanks to the same bacteria also found in dental plaque F. nucleatum may be playing a role in gum inflammation and periodontal disease. This may also help explain why tooth loss is associated with more CVD and total mortality.About a third of colorectal cancers are associated with F. nucleatum. Those cases are often the most aggressive, but until now no one really knew why. In a prior research Dr.Han’s research team discovered that the bacterium makes a molecule called FadA adhesin, triggering a signaling pathway in colon cells that has been implicated in several cancers. They also found that FadA adhesin only stimulates the growth of cancerous cells, not healthy cells. “We needed to find out why F. nucleatum only seemed to interact with the cancerous cells,” says Han.What Dr. Han’s Recent Study FoundIn Dr. Han's most recent study, the researchers found in cell cultures that noncancerous colon cells lack a protein, called Annexin A1, which stimulates cancer growth. They then confirmed both in vitro and later in mice that disabling Annexin A1 prevented F. nucleatum from binding to the cancer cells, slowing their growth. The researchers also discovered that F. nucleatum increases production of Annexin A1, attracting more of the bacteria. “We identified a positive feedback loop that worsens the cancer’s progression,” says. Han. “We propose a two-hit model, where genetic mutations are the first hit. F. nucleatum serves as the second hit, accelerating the cancer signaling pathway and speeding tumor growth.” When the researchers looked at an RNA-sequencing dataset, available through the National Center for Biotechnology Information of 466 patients with primary colon cancer, they found it was the patients with increased Annexin A1 expression who had a worse prognosis, regardless of the cancer’s initial grade and stage or the age or sex of the colon cancer patient (3). Dr. Han’s team is currently looking for ways to develop Annexin A1 as a biomarker for detecting more aggressive cancers and as a potential target for developing new treatments for treating colon and likely other types of cancer associated with more inflammation caused in part by a typical modern diet and inactivity.Bottom Line:  While this research may someday lead to medical treatments that will help treat and perhaps help prevent deaths from aggressive colon cancers it also reinforces what we already know can help reduce the risk of developing and dying from colon cancers, which are the #1 cancer killer of non-smoking Americans. That is to adopt a diet high in whole fruits, vegetables, whole grains, and beans and low in refined grains and low in fat and especially saturated-fat-rich red and processed meats and drinks loaded with refined sugars. Instead drink coffee and tea with little or no added sugars. Limiting high-fat and calorie-dense foods and sugar-rich beverages and staying active will also limit weight gain. This is important as more colon cancers, breast cancers after menopause, and more deadly prostate cancers are all associated with higher body fat stores and especially central adiposity. By James J. Kenney, PhD FACNReferences:

1. Mehta RJ, Nishihara R, Cao Y, et al. Association of dietary patterns with risk of colorectal cancer subtypes classified by Fusobacterium nucleatum in tumor tissue. JAMA Oncol. 2017 Jan 26. doi: 10.1001/jamaoncol.2016.6374.
2. Liu L, Taburg FK, Zhang X, et. al. Diets that promote colon inflammation associate with the risk of colorectal carcinomas that contain Fusbacterium nucleatum. Clin Gastro & Hepatology. 2018;16:1622-31  or http://embor.embopress.org/content/early/2019/03/01/embr.201847638.full.
3. Rubinstein MR, Baik JE, Lagana SM, et. al. Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/??catenin modulator Annexin A1. April 2019 EMBO Reports: DOI 10.15252/embr.201847638.