Tu2042 A Multi-Centre, Randomised, Double-Blind, Controlled Trial Determining the Effect of Additional Fructo-Oligosaccharides on Fecal Microbiota and Short-Chain Fatty Acids Among Critical Care Patients Receiving Enteral Nutrition

Background. Intestinal inflammation is increasingly recognized to support metabolic dysfunction in distant tissues including liver and cardiovascular system. The intestinal microbiota is essential in instructing the systemic immune system and its modulation is recognized to be an important target for treating systemic disorders. Aim. To investigate the effect of administration of VSL#3 in ApoE-/mice challenged with low doses of DSS. Material and methods. Intestinal inflammation was induced by 3-moths administration of 0.2% DSS in drinking water to ApoE-/mice. Mice were randomized to receive vehicle or VSL#3, daily, at the dose of 20 X 109 colony-forming units/kg/day, for 3 months. Results. Administering DSS to ApoE-/mice failed to induce signs and symptoms of colitis (the diarrhea score rose to 1.5) but increased intestinal permeability to dextrane FITC and, while had no effect on serum cholesterol and triglyceride levels, caused a 2-folds increase of AST and ALT levels (p<0.05 versus ApoE-/naive) and resulted in insulin resistance as measured by assessing glucose plasma levels in response to ITT and OGTT (P<0.05 versus naive ApoE-/-. DSS administration associated with intestinal inflammation and development of NASH like lesions in the liver (inflammation and fibrosis scores in Sirius red stained sections) and increased the area of atherosclerotic lesions in the aorta. All these changes were prevented by VSL#3 cotreatment. Specifically, VSL#3 protected against development of histologic features of steato-hepatitis and reduced the extent of aortic plaques. VSL#3 effectively reduced the tendency toward development of aortic plaques also in ApoE-/mice not exposed to DSS. These changes were not related to changes in the dyslipidemic pattern, but VSL#3 effectively reduced insulin resistance in both ApoE-/naive mice and mice exposed to DSS.Conclusions. Intestinal inflammation is a driving factor for development of NASH and atherosclerotic plaques in a genetic model of dyslipidemia. VSL#3 corrects inflammation-driven insulin resistance and protects against development of NASH and atherosclerosis.