Reducing colon cancer risk: how diet switch changes gut microbial metabolism

The gut microbiota is strongly associated with daily food consumption. Hence its composition can serve as a biomarker for nutritional habits as well as disease risks that are related to these habits. Dr. Kishore Vipperla (University of Pittsburgh/USA) presented at the 5th Gut Microbiota for Health World Summit 2016, the results of a fascinating study focussing on connections between diet and colon cancer risk factors.

The findings of Dr. Vipperla and his team show how rapidly the gut microbiota can be altered by a change in diet. But what is more: Their research unveiled that gut bacteria are critically important not only for indicating disease risks but for mediating the link between diet and these risks, thus assigning the gut microbes a place in the causal chain of disease development.

Colon cancer is known to be connected with a western lifestyle and in particular with a diet high in meat and fat but low in fiber. Accordingly, Colon cancer rates are much higher in the western world than in Africa or the Far East. To investigate the possible roles of diet and gut bacteria the scientists carried out a study with a group of 20 healthy middle-aged African Americans – the population with the highest risk of colon cancer in the USA – and another group of 20 participants from rural South Africa, who only very rarely get the disease. The two groups swapped diets under tightly controlled conditions und strict supervision for two weeks: Americans were given a ‘traditional African’ diet, high in fiber and low in meat and fat, while Africans were given a western diet, high in meat and fat, low in fiber. The volunteers underwent colonoscopy examinations as well as gut microbiota analyses before and after the diet switch. At the start, when the groups had been eating their normal diets, almost half of the American subjects had polyps which were subsequently removed as they can turn into tumours. None of the Africans had these abnormal growths.

Biopsy samples taken from the mucosa of different parts of the colon showed a significant suppression of inflammation as well as a decrease in mucosal cell proliferation in the American subjects after they had switched to the “traditional African” low-fat and high-fiber diet. At the same time the food swap induced the reverse process in the guts of the African participants. Thus the risk to develop colon cancer was dramatically increased in the Africans after two weeks on the western diet, as inflammation and the proliferation rate of epithelial cells of the mucosa count as important biomarkers for this condition. These changes were associated with significant alterations in the gut microbial populations. However, these alterations did not affect so much the gut composition of the intestinal microbiota as the metabolic interactions of the intestinal bacteria: The study found that a major reason for the changes in cancer risk was the way in which the bacteria in the gut altered their metabolism to adapt to the new diet. Bacteria known to be butyrate producers and those that can ferment complex carbohydrates seemed to have intensified their collaboration when being provided with a low-fat and high-fiber diet, while the alternative diet reduced these associations. The effects of these different modes of networking were significant: In the American group, the researchers found that the African diet led – among other things – to an increase in the production of the short chain fatty acid (SCFA) butyrate, a bacterial product of fiber metabolism. Like other SCFAs butyrate has important anti-cancer effects including the strengthening of the gut barrier, the support of the immune system and the reduction of pathogens by making conditions in the gut more acidic. On the other hand, secondary bile acids – a bacterial metabolic product which contributes to cancer onset – were reduced. Again the western diet induced the opposite effect in the African subjects.

Prior studies have shown that it takes one generation of westernization for immigrants to raise their originally low colon cancer risk to the rate of the immigration country. “Our findings suggest that it even takes only two weeks for a westernized diet to induce changes in biomarkers of colon cancer risk in the colonic mucosa and the gut microbiota and that gut bacteria metabolism is highly relevant for mediating these changes,” said Dr. Kishore Vipperla. “However, looking at it from the opposite angle this is good news: It is probably never too late to lower one’s colon cancer risk by changing the daily nutritional routine. Our results suggest that increasing the fiber content of the western diet to about 50g per day and reducing fat by half is likely to reduce the colon cancer risk 10-fold. Additionally, gut bacteria now appear as a promising target in order to develop measures to prevent and treat colon cancer.”