Metabolism, Microbiome, Genetics, Epigenetics, and Inflammation on 3 Continents
Worldwide, we currently see an increase in sporadic, non-hereditary colorectal cancer incidence amount younger patients (less than 50 years old). It is well established that colorectal cancer (CRC) carcinogenesis is driven by environmental factors where diet is a strong contributor. Increasingly it is also apparent that diet-microbiome-host interactions are involved in the carcinogenesis. Among other mechanisms a reduction of regulatory effects of commensal bacteria on cell proliferation in colon mucosa dysbiosis may lead to development of precancerous adenomas in the colon.
It has been shown that the bacterial diversity and richness is higher in adenoma patients than healthy controls and has a distinct profile including bacteria thriving of the cancer-related microenvironment. The effect of a westernization of the diet (high fat, low fiber) on CRC risk has been studied in rural Africans compared to African Americans. It seems that a western diet of high fat and low fiber content may induce a shift towards a microbiome dominated by genus Bacteroides from genus Prevotella yielding increased secondary biliary acids instead of butyrate short fatty acids. This is shown to be a more toxic environment driving inflammation and cell proliferation in colon mucosa facilitating tumorigenesis. The findings are however not unambiguous and further investigation is needed to elucidate the mechanisms fully and confirm these interesting findings.
A unique opportunity emerges in the comparison of three distinct populations with disparate environmental exposure. The diet, microbiome and colorectal cancer epidemiology in three settings (Sweden, Uganda and USA) can be compared using cutting edge methodology.