Duysburgh, C. | Search bioRxiv

bioRxiv2022

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

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.

pharmacology and toxicology↗

bioRxiv2021

Alterations in human gut microbiome composition and metabolism after exposure to glyphosate and Roundup and/or a spore-based formulation using the SHIME(R) technology

Despite extensive research into the toxicology of the herbicide glyphosate, there are still major unknowns regarding its effects on the human gut microbiome. As a step in addressing this knowledge gap, we describe for the first time the effects of glyphosate and a Roundup glyphosate-based herbicide on infant gut microbiota using SHIME technology, which mimics the entire gastrointestinal tract. SHIME(R) microbiota culture was undertaken in the presence of a concentration of 100 mg/L (corresponding to a dose of 1.6 mg/kg/day) glyphosate and the same glyphosate equivalent concentration of Roundup, which is in the range of the US chronic reference dose, and subjected to molecular profiling techniques to assess outcomes. Roundup and to a lesser extent glyphosate caused an increase in fermentation activity, resulting in acidification of the microbial environment. This was also reflected by an increase in lactate and acetate production concomitant to a decrease in the levels of propionate, valerate, caproate and butyrate. Ammonium production reflecting proteolytic activities was increased by Roundup exposure. Global metabolomics revealed large scale disturbances in metabolite profiles, including an increased abundance of long chain polyunsaturated fatty acids (n3 and n6). Although changes in bacterial composition measured by qPCR and 16S rRNA sequencing were less clear, our results suggested that lactobacilli had their growth stimulated as a result of microenvironment acidification. Co-treatment with the spore-based probiotic formulation MegaSporeBiotic reverted some of the changes in short-chain fatty acid levels. Altogether, our results suggest that glyphosate can exert effects on human gut microbiota at permitted regulatory levels of exposure, highlighting the need for epidemiological studies aimed at evaluating the effects of glyphosate herbicides on human gut microbiome function.

pharmacology and toxicology↗