Ochoa Kenny Castro, Samant Shalaka, Liu Anjie, Duysburgh Cindy, Marzorati Massimo, Singh Prashant, Hachuel David, Chey William, Wallach Thomas
Division of Pediatric Gastroenterology, SUNY Downstate Health Sciences University, Brooklyn, New York.
Kiwi Biosciences, Cambridge, Massachusetts.
Gastro Hep Adv. 2022 Oct 31;2(3):283-290. doi: 10.1016/j.gastha.2022.10.011. eCollection 2023.
Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in bowel habits. Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (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 FODMAP enzymatic digestion (FODZYME) containing a fructan-hydrolase enzyme (with significant inulinase activity) in a simulated gastrointestinal environment.
Using SHIME (Simulator of the Human Intestinal Microbial Ecosystem), a multi-compartment simulator of the human gut, FODZYME 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.
After 30 minutes, 90% of the inulin was converted to fructose by 1.125 g of FODZYME. Doubling dosage showed no significant improvement in conversion, whereas a half dose decreased performance to 77.2%. Seventy percent 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 production.
FODZYME specifically breaks down inulin in representative gastrointestinal conditions, resulting in decreased gas production while substantially preserving short-chain fatty acid and butyrate production in the model colon. Our results suggest dietary supplementation with FODZYME would decrease intestinal FODMAP burden and gas production.
肠易激综合征（IBS）的特征为腹痛和排便习惯改变。可发酵的低聚糖、双糖、单糖和多元醇（FODMAPs）是吸收不良的短链碳水化合物，可能促使共生微生物产生气体，引发IBS患者的腹痛。低FODMAP饮食可使50%-80%的IBS患者症状改善。然而，这种饮食并非旨在长期维持，因为担心会引发下游营养和微生物问题。在本研究中，我们评估了一种靶向FODMAP酶消化食品补充剂FODMAP酶消化剂（FODZYME）在模拟胃肠道环境中的功能，该补充剂含有一种果聚糖水解酶（具有显著的菊粉酶活性）。
使用人类肠道微生物生态系统模拟器（SHIME），即一种人类肠道多隔室模拟器，在模拟胃肠道条件下进行FODZYME剂量探索试验，评估其水解3克菊粉的酶活性。使用1.125克FODZYME完成全肠道建模，评估菊粉的消化、果糖的吸收、气体产生以及共生微生物行为的其他指标。
30分钟后，1.125克FODZYME将90%的菊粉转化为果糖。剂量加倍后转化率无显著提高，而剂量减半则使转化率降至77.2%。在模拟小肠转运过程中，70%释放的果糖被吸收，同时微生物气体产生相应减少，丁酸和短链脂肪酸产生略有减少。
FODZYME在代表性胃肠道条件下特异性分解菊粉，导致气体产生减少，同时在模型结肠中基本保留短链脂肪酸和丁酸的产生。我们的结果表明，补充FODZYME可减轻肠道FODMAP负担并减少气体产生。
