A9 SHORT-TERM EXPOSURE TO A HIGH SUGAR DIET REDUCES SHORT CHAIN FATTY ACID PRODUCTION AND INCREASES SUSCEPTIBILITY TO COLITIS

Western diets high in refined sugar have been associated with increased susceptibility to inflammatory bowel disease (IBD), possibly through dietary-induced alterations in gut microbial composition and/or function. Short chain fatty acids (SCFA) including acetate and butyrate are produced from indigestible fibers by microbial fermentation and are critical to gut homeostasis. The aim of this study was to examine the effects of short-term exposure to high sugar diets on host susceptibility to colitis and to determine the role of SCFA in disease susceptibility. At 6–8 weeks of age, wild-type 129/SvEv mice were placed on chow (CH) or high sugar diet (HS) (50% sucrose: AIN76A). Fiber content was 5% (cellulose) and 5.3% (crude fiber) in the HS and chow diets respectively. After two days on the diet, mice were administered dextran sodium sulfate (DSS) for 5 days and water for 2 days (n=4–6 mice for all groups). Disease activity index (DAI) was determined by assessing weight loss, blood in stool, and stool consistency. At day 2 (prior to DSS and after 2 days on diet) and at d7, colons were homogenized for cytokine expression by MesoScale discovery platform. Short chain fatty acid (SCFA) concentrations were measured in stool after 2 days on diet. In separate cohorts, sodium acetate (300 mM) was added to drinking water concurrently with beginning the HS-diet followed by DSS. After 2 days on a HS diet, mice had reduced levels of fecal acetate (p<0.05) and butyrate (p<0.0001) but did not show any differences in basal levels of colonic cytokines Mice on the HS diet demonstrated increased susceptibility to DSS colitis compared with chow fed mice with increased weight loss, earlier blood in stool and worsened stool consistency. This was associated with significantly enhanced levels of colonic IFNγ, IL-1β, IL-6, TNFα, and IL-12p70 (p<0.05 compared with chow-fed). Mice which received acetate in their drinking water concurrently with HS diet demonstrated a similar susceptibility to colitis as did the chow-fed mice, with reduced blood in stool, less weight loss, and improved stool consistency compared with HS fed mice. An acetate-induced reduction in disease susceptibility was associated with reduced levels of pro-inflammatory cytokines to mirror those in the chow-fed group. A short-term exposure to a high sugar diet significantly reduces levels of acetate and butyrate, even in the presence of similar amounts of fiber. This loss of short chain fatty acids increases susceptibility to chemically-induced colitis and can be alleviated by acetate indicating a key role for microbial fermentation processes in gut protection from insults. CAG, CIHR

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