Evidence is mounting that some bowel cancers are caused by bacteria. One microbe seems to trigger a distinct type of mutation in our DNA, which can be seen in up to one in 10 cases of colon cancer. “It’s the first bacteria ever shown to change DNA and be carcinogenic,” says Hans Clevers of the Hubrecht Institute in Utrecht, the Netherlands. Colon cancers are usually seen as stemming from random genetic mutations, with smoking and an unhealthy diet raising our risk. But more recently, suspicions have grown about certain gut bacteria, including a strain of E. coli that produces a substance that can damage our DNA. This strain, called pks+ E. coli, is more common in the faeces of people who have had colon cancer, but it is unclear if it directly causes the tumours or just grows better in the guts of people who had already developed cancer. To investigate, Clevers and his team injected the bacteria into human gut cells growing in tiny clumps known as organoids over five months. They found the microbe triggers distinct patterns of DNA damage: of the four “letters” of the DNA code, the mutations happen at a particular two-letter combination. The group then looked at two previous studies in which the genes of nearly 6000 tumours, mostly from the colon, had been sequenced. Between 5 and 10 per cent of people with colon cancer had this same pattern of mutations, but it wasn’t there in the other types of tumour. “We feel that’s very strong evidence that these bacteria are indeed the cause of the cancers in those patients,” says Clevers. “I won’t say this is the clincher, but this takes a very strong step forward,” says Cynthia Sears of Johns Hopkins University in Maryland. If the results are confirmed, people could get rid of the cancer-causing bacteria by taking antibiotics, and then take probiotic capsules containing the safe E. coli strain to stop the dangerous one from returning, says Clevers. In a separate study, another group has shown that a lack of certain bacteria may be causing a different disease called ulcerative colitis, where the immune system seems to attack the gut, leading to inflammation. Aida Habtezion at Stanford University in California and her colleagues found that people with this condition have a less diverse community of gut bacteria, and lack a particular class of biochemicals in their faeces called secondary bile acids. These compounds are made by a type of bacteria that people with ulcerative colitis lack. “That really stood out,” says Habtezion. Her team gave the bile acids to mice with a similar condition to ulcerative colitis and found that their gut inflammation lessened. The group has now started a trial of one of the bile acids in 15 people with ulcerative colitis to see if it reduces their symptoms. Results are due next year. The researchers have been able to move quickly into human tests as the bile acid is already used as an oral medicine for treating liver disease. To be most effective, however, Habtezion believes it should be delivered into the colon through an enema. Journal reference: Nature, DOI: 10.1038/s41586-020-2080-8; Cell Host & Microbe, DOI: 10.1016/j.chom.2020.01.021 Source
