Improving tolerance for FODMAPs using modified celluloses: defining the role of gelation in reducing gas production in vitro and in vivo

使用改性纤维素提高 FODMAP 的耐受性：定义凝胶化在减少体外和体内气体产生中的作用

• 批准号: MR/W026295/1
• 负责人: Robin Spiller
• 金额: $ 184.83万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW026295%2F1
• 关键词: Improving; tolerance; FODMAPs; using; modified

Although fibre is known to be an important part of our diet, we eat too little for our health. In part, this is because of the discomfort that can arise from consuming it, including bloating as a result of gas build up in the bowel. A group of dietary carbohydrates called FODMAPs are rapidly fermented in the large bowel (colon) producing gases as we have shown recently using MRI (Magnetic Resonance Imaging). Low FODMAP diets improve IBS symptoms but such diets are difficult to follow and may have undesirable effects on gut bacteria. Psyllium, a commonly prescribed fibre improves IBS patients' symptoms and reduces the rise in colonic gas volumes after consuming a commonly dietary FODMAP called inulin. Psyllium is a dietary fibre which forms a gel when added to water but exactly how psyllium alters colonic fermentation is unknown. We have developed a laboratory model colon which simulates conditions in the colon and allows us to measure the breakdown products of inulin including gas, something very difficult / impossible in actual patients because the colon is so inaccessible. We believe that psyllium acts by forming a gel, trapping inulin thereby excluding colonic bacteria and hence slowing and redirecting colonic fermentation to produce less gas but more short chain fatty acids (SCFAs). This could retain the metabolic benefits associated with SCFAs (reducing obesity / type II diabetes) while reducing adverse effects associated with excessive gas. Celluloses are safe, inexpensive dietary fibres, already widely used in the food industry which can be modified to vary viscosity and the ability to form gels to allow us to compare the effect of viscosity (resistance to flow) with that of gel formation using chemically similar substances. Gels are likely to exclude bacteria in a way that increased viscosity alone will not do.STUDY 1A: We will initially confirm our original findings that psyllium reduces breath hydrogen response after 20g inulin and then see if a cellulose mix of equal viscosity has a similar effect and how this compares to a cellulose preparation of equal viscosity that also gels at body temperature. We will do this by giving healthy volunteers 500ml of water and 20g inulin to which is added either a) psyllium b) cellulose mix of viscosity equal to psyllium c) cellulose of equal viscosity but modified to form a gel or d) inulin alone. We believe that high viscosity alone will not produce the effect but gelation will. If true we will then use the gelling cellulose to do STUDY 1B to work out the optimum dose to use in subsequent studies. STUDY 2: This will use our colonic model to assess the effect of the different cellulose preparations on fermentation pathways in the laboratory. STUDY 3: Will use stool samples from Study 1 subjects in our laboratory model colon to correlate gas production with other break down products of inulin including SCFAs to see how these alter with differing gas production. STUDY 4: These MRI studies will measure how the most effective cellulose from Studies 1 alters flow of inulin into the colon and gas production. We will also measure acidity in the colon in response to inulin and how the cellulose mix changes it, using a 'Smart pH pill' (a swallowed pill which passes through the gut emitting a radio signal indicating acidity). STUDY 5: Will use the results from Study 4 to accurately model flow rates, acidity and concentrations in our colonic model and measure the changes in SCFA production caused by the cellulose. STUDY 6: We will give the cellulose with inulin daily for 3 weeks to IBS patients before assessing gas and colonic volumes using MRI, relevant bowel symptoms (gas, pain, bloating) and stool fermentation pathways using our model colon. If our studies are successful celluloses could be easily added to ready prepared foods to allow consumption of large molecular weight FODMAPs without causing adverse symptoms. They could also be prescribed as a treatment.

虽然纤维是我们饮食的重要组成部分，但我们吃得太少对我们的健康不利。在某种程度上，这是因为食用它会引起不适，包括由于肠道中气体积聚而引起的腹胀。一组称为FODMAPs的膳食碳水化合物在大肠（结肠）中迅速发酵，产生气体，正如我们最近使用MRI（磁共振成像）所显示的那样。低FODMAP饮食改善IBS症状，但这种饮食难以遵循，可能对肠道细菌产生不良影响。欧车前是一种常用的处方纤维，它可以改善IBS患者的症状，并在食用一种称为菊粉的常见膳食FODMAP后减少结肠气体体积的上升。欧车前是一种膳食纤维，当加入水中时会形成凝胶，但欧车前究竟如何改变结肠发酵尚不清楚。我们已经开发了一种实验室模型结肠，它模拟结肠中的条件，并允许我们测量菊糖的分解产物，包括气体，这在实际患者中非常困难/不可能，因为结肠是如此难以接近。我们认为，车前子通过形成凝胶，捕获菊粉，从而排除结肠细菌，从而减缓和重定向结肠发酵，以产生更少的气体，但更多的短链脂肪酸（SCFA）。这可以保留与SCFA相关的代谢益处（减少肥胖/II型糖尿病），同时减少与过量气体相关的不良影响。纤维素是一种安全、廉价的膳食纤维，已经广泛用于食品工业，可以对其进行改性以改变粘度和形成凝胶的能力，从而使我们能够比较粘度（流动阻力）与使用化学相似物质形成凝胶的效果。凝胶可能会以一种增加粘度的方式排除细菌。研究1A：我们将首先确认我们最初的发现，即20 g菊粉后，车前子会降低呼吸氢反应，然后看看相同粘度的纤维素混合物是否具有类似的效果，以及与同样粘度的纤维素制剂相比，这是如何在体温下凝胶化的。我们将通过给予健康志愿者500 ml水和20 g菊粉来实现这一点，其中加入a）车前子B）粘度等于车前子的纤维素混合物c）粘度相同但改性形成凝胶的纤维素或d）单独的菊粉。我们认为，高粘度本身不会产生这种效果，但胶凝作用会。如果属实，我们将使用胶凝纤维素进行研究1B，以确定后续研究中使用的最佳剂量。研究2：这将使用我们的结肠模型来评估不同纤维素制剂对实验室发酵途径的影响。研究3：将在我们的实验室模型结肠中使用来自研究1受试者的粪便样本，将气体产生与菊粉的其他分解产物（包括SCFA）相关联，以了解这些产物如何随不同气体产生而变化。研究4：这些MRI研究将测量研究1中最有效的纤维素如何改变菊粉流入结肠和气体产生。我们还将测量结肠中对菊粉的反应以及纤维素混合物如何改变它的酸度，使用“智能pH药丸”（一种吞咽的药丸，通过肠道发出指示酸度的无线电信号）。研究5：将使用研究4的结果来准确地模拟我们结肠模型中的流速、酸度和浓度，并测量由纤维素引起的SCFA产生的变化。研究6：我们将每天给予IBS患者纤维素和菊粉，持续3周，然后使用MRI评估气体和结肠体积，使用我们的模型结肠评估相关肠道症状（气体，疼痛，腹胀）和粪便发酵途径。如果我们的研究是成功的，纤维素可以很容易地添加到现成的食品，使消费大分子量的FODMAPs不会引起不良症状。它们也可以作为治疗处方。

项目成果

P289 Modelling psyllium's inhibitory effect on gas production after FODMAP (Inulin) by using divided doses: a 24-hour, randomised, placebo-controlled trial

P289 使用分剂量模拟车前子对 FODMAP（菊粉）后产气的抑制作用：一项 24 小时随机安慰剂对照试验

• DOI: 10.1136/gutjnl-2023-bsg.355
• 发表时间: 2023
• 作者: Alhasani A