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Pharmacology & ToxicologybioRxiv
Preprint

In-Vitro Efficacy of Targeted FODMAP Enzymatic Digestion in a High-Fidelity Simulated Gastrointestinal Environment

K. Castro Ochoa, S. Samant, A. Liu, C. Duysburgh, M. Marzorati, D. Hachuel, T. Wallach

Abstract

IntroductionIrritable bowel syndrome (IBS) is characterized by abdominal pain and changes in bowel habits. FODMAPs are poorly absorbed short-chain carbohydrates that may drive commensal microbial gas production, promoting abdominal pain in IBS. Low-FODMAP diet can result in symptomatic improvement in 50-80% of IBS patients. However, this diet is not meant to be sustained long term, with concern for downstream nutrition and microbial issues. In this study, we evaluate the function of a targeted FODMAP enzymatic digestion food supplement FODZYME(R) containing an fructan hydrolase enzyme in a simulated gastrointestinal environment. MethodsUsing SHIME(R), a multi-compartment simulator of the human gut, FODZYME(R) dose finding assay in modeled gastrointestinal conditions assessed enzymatic ability to hydrolyze 3 g of inulin. Full intestinal modeling assessing digestion of inulin, absorption of fructose, gas production and other measures of commensal microbial behavior was completed using 1.125 g of FODZYME(R). ResultsAfter 30 minutes, 90% of the inulin was converted to fructose by 1.125 g of FODZYME(R).Doubling dosage showed no significant improvement in conversion, whereas a half dose decreased performance to 77.2%. 70% of released fructose was absorbed during simulated small intestinal transit, with a corresponding decrease in microbial gas production, and a small decrease in butyrate and short chain fatty acid (SCFA) production. DiscussionFODZYME(R) specifically breaks down inulin in representative gastrointestinal conditions, resulting in decreased gas production while substantially preserving SCFA and butyrate production in the model colon. Our results suggest dietary supplementation with FODZYME(R) would decrease intestinal FODMAP burden and gas production.

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