TARGETED GENE EXPRESSION AND CONCENTRATIONS OF SHORT-CHAIN FATTY ACIDS IN RESPONSE TO HIGH FIBER SUPPLEMENTATION: RESULTS OF THE ALASKA FIBER INTERVENTION RESEARCH STUDY (FIRST)

Background: Colorectal cancer (CRC) stands as a globally prevalent yet preventable malignancy. Recent discoveries suggest a substantial reduction in colon cancer risk with a daily intake of 50 grams of fiber, holding promise for potential protection against CRC. Our study delves into unraveling the intricate mechanisms behind this phenomenon, specifically examining fiber's impact on butyrate production, bile acid production, and the microbial environment linked to carcinogenesis. Butyrate, a short-chain fatty acid (SCFA) synthesized in the colon through bacterial fermentation, assumes a central role. This research aims to decipher the intricacies of butyrate dynamics by scrutinizing key genes responsible for its synthesis (bcoA and buk) and evaluating individual SCFAs, recognizing their diverse effects on digestive health. Furthermore, considering the implication of bile acids (BAs) in colon cancer development, our study includes the measurement of the bacterial gene (baiCD) associated with BA production and an exploration of microbes linked to CRC (fusobacterium, and B. Wadsworthia). We aim to elucidate the potential of a high-fiber diet in mitigating CRC risk.
Methods: In a 4-week randomized, double-blind, placebo-controlled trial, forty-eight healthy adult individuals of Alaska Native race (Table 1) were assigned to either a high-fiber supplement containing 70g high-amylose maize starch (42g resistant starch [RS]) (n=23) or 35g fully digestible starch (DS) for the placebo group (n=25). Quantitative assessments of targeted bacterial genes, fecal SCFA, and BAs were conducted on pre- and post-supplementation stool samples. The study's primary objective was to determine if RS induced changes in targeted gene and individual SCFA concentrations. Statistical analyses employed t-tests to assess changes.
Results: Statistically significant changes were found in all genes: for the RS group, relative to the DS group, increases were found in buk, mcrA, fusobacterium, and B. Wadsworthia; whereas, decreases were found in bcoA, baiCD, and dsrA. For SCFAs, the RS group relative to the DS group, significant decreases were found in Isobutyric Acid, Isovaleric Acid, and Isohexanoic Acid, whereas an increase was found in Hexanoic Acid. Butyric acid increased; however, the increase was not statistically significant. (Figure 1A-F). The results indicate variations in mean values between digestible and resistant starch for different bile acids. Notably, no statistically significant differences were observed across the bile acids.
Conclusions: The study reveals significant changes in gene expression and short-chain fatty acids between digestible and resistant starch groups, indicating a notable impact on key factors associated with colorectal health. Despite variations in mean values for BAs, no significant differences were observed across the studied bile acids.