Gut and cancer: what the gut microbiota protects against, what harms, and why it matters in cancer treatment

Healthy state

The lining of the gut renews itself completely every few days. For this, stem cells deep in the pits of the gut wall divide constantly. Each division can introduce an error in the genome, and usually the body repairs or removes the affected cell. If certain errors build up over years, a polyp can form and, very slowly, colorectal cancer can develop from it. Because this takes so long, colorectal cancer can often be prevented by screening colonoscopies: polyps are simply removed during the procedure.

What reaches the colon shapes the environment of these cells. Bacteria ferment fibre into short-chain fatty acids Short-chain fatty acids Acids such as acetate, propionate and butyrate that gut bacteria make from fibre. They nourish the gut wall and act throughout the body. More in the chapter “Butyrate and other short-chain fatty acids”, above all butyrate Butyrate A short-chain fatty acid and the main energy source for the cells of the colon wall. It strengthens the barrier and dampens inflammation. More in the chapter “Butyrate and other short-chain fatty acids”. Healthy gut cells use butyrate as their main fuel; it seals the wall and calms the immune system. A large analysis of 185 observational studies found that people who ate the most fibre had a 15 to 30 percent lower risk of colorectal cancer and other chronic diseases. The benefit was clearest from 25 to 29 grams a day.

An exchange experiment showed how quickly diet changes the gut environment. Colorectal cancer is more than ten times as common in African Americans as in people in rural South Africa. For two weeks, African Americans ate a high-fibre, low-fat African diet and South Africans a high-fat, low-fibre Western diet. The values reversed almost like a mirror image: in the African Americans, butyrate production rose and fewer secondary bile acids Bile acids Substances made by the liver that make fat digestible. About 95 percent are reabsorbed in the last part of the small intestine; gut bacteria transform the rest. More in the chapter “Bile acids: when bile causes diarrhoea”, which irritate the lining, were formed. Markers of cell growth in the lining also fell.

The gut microbiota Microbiome, gut microbiota The community of all microbes in the gut, mainly bacteria, plus viruses, fungi and archaea. Most live in the colon. More in the chapter “Building microbial diversity” also trains the immune system, which can recognise and fight cancer cells too. This shows in immunotherapy with so-called checkpoint inhibitors, which release the brake on immune cells. Whether they work was linked to the gut microbiota in several studies. Among 128 people with melanoma, those who ate a lot of fibre lived longer without their disease progressing, most clearly when they did not take probiotics Probiotics Live microorganisms that are meant to provide a benefit in sufficient amounts. The effect depends on the individual strain. More in the chapter “Using fermented foods well”.

Disrupted state: causes and effects

Colorectal cancer is one of the most common cancers. Strikingly, it is increasing in people under 50: in many countries the number has doubled over the last two decades. Why is not clear. Diet, overweight, antibiotics and the gut microbiota in childhood are being discussed.

One hot lead points to bacteria. Some strains of Escherichia coli carry a gene cluster called pks and use it to make colibactin, a substance that damages DNA. When researchers exposed lab-grown mini-guts to such bacteria for five months, they left a typical pattern of DNA errors. Exactly this pattern was found in some of almost 6,000 human cancer genomes, especially in colorectal cancer. A study of 981 colorectal cancer genomes from 11 countries found the colibactin pattern 3.3 times more often in people who fell ill before 40 than in those over 70. It had arisen early in cancer development. The researchers therefore suspect that contact with these bacteria in childhood contributes to the rise in younger people. This is not proven.

A second suspect is Fusobacterium nucleatum, a bacterium from the mouth that is particularly common in colorectal tumours. It even travels along into secondary tumours in the liver. The same strains were found in the tumour as in the mouth of the same person. In mice with human colorectal cancer, an antibiotic reduced the fusobacteria and slowed tumour growth. Whether fusobacteria cause cancer or just feel at home in the tumour is unclear. According to a meta-analysis Meta-analysis An analysis that combines the results of several studies. It is only as good as the studies it includes. , a saliva test is not suitable for detecting colorectal cancer.

A third bacterium matters in practice: Streptococcus gallolyticus. When it gets into the blood, for example in an infection of the heart valves, around 60 percent of those affected also had a polyp or colorectal cancer in studies. Such a finding is therefore a reason for a colonoscopy.

Meat and fat act through several routes. The WHO’s cancer research agency classifies processed meat such as sausage and ham as carcinogenic and red meat as probably carcinogenic. Each 50 grams of processed meat a day raises the risk of colorectal cancer by about 18 percent. High-fat diets also stimulate bile release. Gut bacteria turn the bile acids into secondary bile acids such as deoxycholic acid, which irritate the lining and stimulate cell growth in experiments.

Long-lasting inflammation also raises the risk. In ulcerative colitis, the risk of colorectal cancer is about two thirds higher than in the rest of the population. In the stomach, Helicobacter pylori is the main trigger of stomach cancer. In six randomised trials Randomised trial A study in which chance decides who gets the treatment and who does not, for comparison. This makes results particularly reliable. , mostly from Asia, treatment against Helicobacter lowered the stomach cancer risk of healthy infected people by about one third.

In cancer treatment, a disturbed gut microbiota can weaken the effect. People who received antibiotics around the start of immunotherapy responded less well in one study. When stool from patients who responded to therapy was transferred into germ-free mice, it also worked better there; with stool from non-responders it did not. In a first study in humans, 6 of 15 people with melanoma whose immunotherapy had failed responded again after a stool transfer from patients with a good response.

Conversely, cancer treatment affects the gut. Chemotherapy and radiation to the pelvis cause diarrhoea in 50 to 80 percent of those treated, because they also hit the rapidly dividing cells of the gut lining. This can lead to loss of fluid and nutrients and to breaks in treatment.