Can Gut Microbes Cause Cancer?

            The Western-style diet is chock full of high fat, processed and refined foods that often cause systemic damage to the human body. One particular effect that high fat foods have on the body involves the microbes in the gastrointestinal tract. Many studies have shown the association between the colonization of a subset of microbes in the gut and colorectal and gastric cancer onset. The question of interest is: can what we eat really lead to the onset of gastrointestinal cancer?

            Interestingly, diet directly affects the types of bacteria that typically colonize the gut. Though both extrinsic (e.g., diet, medications) and intrinsic factors (genetics, metabolic regulation, etc.) determine the bacterial composition within the gut, the former has the most predominant effect (1). For instance, fiber-rich foods such as nuts, legumes, grains, vegetables and fruit are associated with the growth of Bifidobacterium, Lactobacillus and lactic acid bacteria. These foods, also known as prebiotics, lead to the production of butyrate, acetate, propionate and short chain fatty acids by obligate anaerobes such as those in the Firmicutes and Bacteroidetes phyla (1). On the other hand, the consumption of high fat foods leads to the increase in facultative anaerobes in the gut such as Enterobacteriaceae, which are abundant in the feces of individuals on high fat diets (2). Thus, a healthy intestinal environment has a hypoxic colonic surface, generally, while an unhealthy gut contains more terminal electron receptors such as oxygen and nitrate in the colonic epithelia, which facultative anaerobes use to survive in the gut (2). Ultimately, it’s safe to say the cliché: “you are what you eat”, as the microbes in your gut will tell a great deal about what you generally consume.

So, what is the link between these microbes and cancer? The answer is not so simple, but a recent Science paper might hold some insight. In this paper, researchers sought to determine how diet-induced changes in intestinal physiology alter the metabolic capacity of the microbiota. Using a high-fat and low-fat feeding model, they showed that high-fat diet fed mice had gut epithelial metaplasia, increased abundance of [1], mucosal inflammation, reduced mitochondrial activity, reduced hypoxia, and that a prolonged high-fat diet escalates Escherichia coli choline metabolism (3). Interestingly, several species of E.coli (e.g pks+) and other Enterobacteria are detected more frequently in patients with colorectal cancer (CRC) compared to healthy individuals. These genotoxic metabolites, which damage DNA and are found to induce mutation in genes (e.g Adenomatous polyposis coli-APC) (2, 4). Mutations that disrupt APC signaling pathways are found in 80% of CRC patients.  The fact that approximately 65% of CRC cases are sporadic, and environmental factors such as diet are likely to play a major role in its onset should be a warning to individuals who tend to ignore their nutritionists and doctors!

References:

1. Leeming ER, Johnson AJ, Spector TD, Le Roy CI. Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration. Nutrients. 2019 Nov 22;11(12):2862. doi: 10.3390/nu11122862 
2. Foegeding NJ, Jones ZS, Byndloss MX. Western lifestyle as a driver of dysbiosis in colorectal cancer. Dis Model Mech. 2021 May 1;14(5): doi: 10.1242/dmm.049051.
3.  Yoo W, Zieba JK, Foegeding NJ, Torres TP, Shelton CD, Shealy NG, Byndloss AJ, Cevallos SA, Gertz E, Tiffany CR, Thomas JD, Litvak Y, Nguyen H, Olsan EE, Bennett BJ, Rathmell JC, Major AS, Bäumler AJ, Byndloss MX. High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide. Science. 2021 Aug 13;373(6556):813-818. doi: 10.1126/science.aba3683.
4. Dougherty MW, Jobin C. Shining a Light on Colibactin Biology. Toxins (Basel). 2021 May 12;13(5):346. doi: 10.3390/toxins13050346.