Society: AGA

Background: Diets high in animal fat and low in plant fiber increase colorectal cancer (CRC) risk, while diets high in fiber, but low in animal fat, are protective. Bacteria present in the colon produce beneficial and harmful metabolites from our diets. Fiber is fermented by these bacteria, producing short-chain fatty acids (SCFA). One of them, butyric acid, is the major energy source for colonic cells and has strong anti-inflammatory/anti-carcinogenic properties. Excess consumption of animal fats is known to increase levels of carcinogenic secondary bile acids in the colon, namely lithocholic acid (LCA) and deoxycholic acid (DCA). Alaska Native (AN) people, at highest risk globally for CRC, were interested in whether increasing dietary fiber intake could reduce CRC risk, as their diets are high in meat and fat, but deficient in fiber.
Purpose: Evaluate whether a fiber supplement added to the usual diet of AN volunteers will increase the microbial production of butyrate and suppress fecal bile acids, thus reducing CRC risk.
Methods: Forty-eight healthy AN adult volunteers were enrolled a 4-week randomized, double-blind, placebo-controlled trial in which they received either a resistant starch supplement, RS, a non-chemically modified food starch extracted from high amylose corn, or a digestible starch supplement, DS, an isocaloric amylopectin supplement, occurring naturally as a branched glucose polymer. Quantitation of fecal SCFA and bile acids was performed by on stool samples collected pre- and post-supplementation by gas chromatography-flame-ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS) (Figure 1). The primary endpoint was to evaluate whether RS could suppress epithelial proliferation measured by immunohistological staining of proliferative cells with Ki67 in well orientated crypts. The magnitude of the Ki67 suppression was also used to define clinically significant responses of <20%, termed “responders” (Figure 2). Statistical analyses were performed with paired t-tests on all SCFA and bile acids.
Results: Butyrate levels showed increases in both groups, significant in the RS group. Conversely, there were reductions in LCA and DCA in both groups, significant for DCA in the RS group.
Conclusions: RS significantly increased fecal anticarcinogenic butyrate and suppressed inflammatory and potentially carcinogenic secondary bile acids which might explain the suppression of cancer biomarkers in the colonic mucosa. Interestingly, DS had similar but less pronounced effects. It is noteworthy that previous dietary analysis indicated the AN diet was also low in carbohydrate (Ocvirk et al. AJCN 2016) and so it is possible that their diet could be improved by the increased consumption of all forms of complex carbohydrate.
Acknowledgements: NIH grant R01 CA204403

Soren Ocvirk

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