Figure 3.

Dietary fiber protects against colorectal cancer in a microbiota- and butyrate-dependent manner in a gnotobiotic mouse model. Mice were colonized with several bacteria that either excluded or included a butyrate producer as indicated at the top. A wild-type and mutant strain of the butyrate producer was utilized in separate gnotobiotic isolators (depicted by boxes around each group of mice). In each isolator, the mice received control or high-fiber diets (6% fructo-oligosaccharides/inulin but otherwise virtually identical to the control diet) except for a butyrate-fortified diet in the isolator at the far right. Arrows at the bottom indicate relative levels of luminal butyrate along with global histone acetylation levels and tumor burden after tumorigenesis was initiated 5 months earlier. Butyrate production was attenuated, but not completely abolished, in the mutant strain when provided a high-fiber diet as denoted by one upward butyrate arrow instead of a downward arrow or two upward arrows. The yellow ovals highlight experimental conditions that yield a lower tumor burden, and this correlates with higher butyrate levels and histone acetylation levels.