Dietary Fiber Treatment Corrects the Composition of Gut Microbiota, Promotes SCFA Production, and Suppresses Colon Carcinogenesis

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.

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“…The diet compositions are presented in Table S1, Supporting Information. Different percentages of fiber 5–20% were used. The dose is relevant to human diets if the body surface area conversion factor (12.3) between mouse and human is taken into consideration.…”

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“…A biological observation matrix (BIOM) (McDonald et al, 2012) was generated at each taxonomic level from phylum to species ("make OTU table" algorithm) and analyzed and visualized using the software packages Primer7 and the R programming environment (Clarke, 1993;R Development Core Team, 2013). Following sequencing, computational bioinformatics analysis was used to describe the bacterial diversity, community structure, and composition of the microbiota, as described previously (Bishehsari et al, 2018;Mahdavinia et al, 2018;Xiao et al, 2019). Dominant phylum, family, and genus bacteria were determined using a relative abundance threshold >2%, within the sex of monkeys.…”

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“…React with glycans of glycoconjugates of various types on the cell membranes of the enterocytes[117], or 3) Be processed differentially by the gut microflora resulting in (a) Production of useful short-chain fatty acids (SCFA), which have beneficial effects[123]. (b) Variation of the composition of the gut microbiota (positively or negatively], which will consequently influence inflammation[124]. Be absorbed into the internal milieu by diffusion or pinocytosis where they (a) Are presented to the APCs (antigen-presenting cells), such as dendritic cells, which will present the glycan for the generation of specific anti-glycan antibodies (AGA)[34,125].…”