Western-style diets have been implicated in triggering inflammatory bowel disease activity. The aim of this study was to identify the effect of a short-term diet high in sugar on susceptibility to colitis. Adult wild-type mice were placed on chow or a high sugar diet (50% sucrose) ± acetate. After two days of diet, mice were treated with dextran sodium sulfate (DSS) to induce colitis. Disease severity was assessed daily. Colonic tissues were analyzed for cytokine expression using the MesoScale discovery platform. Intestinal dextran permeability and serum lipopolysaccharide levels (LPS) were measured. Gut microbiota were analyzed by 16s rRNA sequencing and short chain fatty acid (SCFA) concentrations by gas chromatography. Bone marrow-derived macrophages (BMDM) were incubated with LPS and cytokine secretion measured. Mice on a high sugar diet had increased gut permeability, decreased microbial diversity and reduced SCFA. BMDM derived from high sugar fed mice were highly responsive to LPS. High sugar fed mice had increased susceptibility to colitis and pro-inflammatory cytokine concentrations. Oral acetate significantly attenuated colitis in mice by restoring permeability. In conclusion, short term exposure to a high sugar diet increases susceptibility to colitis by reducing short-chain fatty acids and increasing gut permeability.

Background: 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. Aims: 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. Methods: 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. Results: 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. Conclusions: 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 Downloaded from https://academic.oup.

THE associaltioii in young people of enlirged liver iecul'ling ascites aid chronic adherent pericardium niot a, ve'y comI1111on condition. The earliest reported was probably time one reporte(d by Van Deen in 1846,-a more complete descriptioni was given in 1896 by the symptom-coniplex isoften described as-Pick's disease, om' Pick's l)eLi(alditic p)selllo-Cilllosis of the moclein textbooks of medicinle do-nomaoe mentionthis disease, but many monographs have -bee4 w-r itten oln it, and mlost of-the references in this abstracted from a lengthy monograph by Kelly printedI in tIle .Anerican-Journal of-the Medical Sci%nces. Time disease presents many pi'oblems yet u'nsollved,notably the true cau1se of the conditioni and the relationship it bears to two other diseases-namely, Coneato's the one hand, and "Zuckergussleber," observed in 1852,, and graphically named sugar-iced liver Curschmmann in 1884, on the other.

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