Abstract
Epidemiological studies propose a protective role for dietary fiber in colon cancer (CRC). One possible mechanism of fiber is its fermentation property in the gut and ability to change microbiota composition and function. Here, we investigate the role of a dietary fiber mixture in polyposis and elucidate potential mechanisms using TS4Cre × cAPCl°x468 mice. Stool microbiota profiling was performed, while functional prediction was done using PICRUSt. Stool short-chain fatty acid (SCFA) metabolites were measured. Histone acetylation and expression of SCFA butyrate receptor were assessed. We found that SCFA-producing bacteria were lower in the polyposis mice, suggesting a decline in the fermentation product of dietary fibers with polyposis. Next, a high fiber diet was given to polyposis mice, which significantly increased SCFA-producing bacteria as well as SCFA levels. This was associated with an increase in SCFA butyrate receptor and a significant decrease in polyposis. In conclusion, we found polyposis to be associated with dysbiotic microbiota characterized by a decline in SCFA-producing bacteria, which was targetable by high fiber treatment, leading to an increase in SCFA levels and amelioration of polyposis. The prebiotic activity of fiber, promoting beneficial bacteria, could be the key mechanism for the protective effects of fiber on colon carcinogenesis. SCFA-promoting fermentable fibers are a promising dietary intervention to prevent CRC.
Highlights
Colon cancer (CRC) is the second leading cause of death from cancer
Using a predicative assessment of the microbial community functional potential (PICRUSt), with a specific a priori hypothesis of examining short-chain fatty acids (SCFA)-related pathways, we identified six pathways and 30 KOs that had significantly increased abundances in high fiber-fed mice compared to chow-fed mice (Figure 5) (Tables S1 and S2)
Our findings indicate that insoluble fermentable fiber increases putative SCFA-producing bacteria, SCFA-related functional pathways, SCFA metabolites, and positively correlates with putative beneficial microbial taxa
Summary
Colon cancer (CRC) is the second leading cause of death from cancer. Genetic susceptibility plays an important role in the pathogenesis of CRC, environmental factors play an even bigger role in the development of colon cancer. Among lifestyle-related factors, dietary habits are strongly associated with the disease risk. Dietary fiber (i.e., cereal, fruit, and whole grains) has been shown to significantly modulate the CRC risk [3,4]. Fibers are indigestible in the gastrointestinal tract until arrival to the colon, where they are mainly fermented, resulting in the formation of short-chain fatty acids (SCFA) such as acetate, propionate, and butyrate (in a ratio of 3:1:1 approximately). Several anti-cancerous mechanisms have been shown for SCFAs, including their direct effects on cancerous epithelial cells, or anti-inflammatory effects in the colon as reviewed elsewhere [5,6]
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