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

虽然众所周知，纤维是我们饮食中的重要组成部分，但我们吃得太少了，不利于我们的健康。这在一定程度上是因为食用它会引起不适，包括肠道内积聚的气体导致的腹胀。正如我们最近使用磁共振成像(MRI)所显示的那样，一组被称为FODMAP的饮食碳水化合物在大肠(结肠)中迅速发酵，产生气体。低FODMAP饮食可以改善IBS症状，但这种饮食很难遵循，可能会对肠道细菌产生不良影响。木耳，一种常用的处方纤维，在摄入了一种常见的饮食中称为菊粉的FODMAP后，改善了IBS患者的症状，并减少了结肠气体容量的增加。木耳是一种膳食纤维，当加入水中时会形成凝胶，但木耳到底是如何改变结肠发酵的尚不清楚。我们已经开发了一种实验室模型结肠，它模拟了结肠中的条件，使我们能够测量包括气体在内的菊粉的分解产物，这在实际患者中是非常困难/不可能的，因为结肠是如此难以接近。我们认为，木耳的作用是形成一种凝胶，捕获菊粉，从而排除结肠细菌，从而减缓和重新定向结肠发酵，以产生更少的气体，但更多的短链脂肪酸(SCFA)。这可以保留与单链脂肪酸相关的代谢益处(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，已广泛用于食品工业，可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(抗流性)的影响与使用化学相似物质形成凝胶的效果。凝胶可能会以一种单独增加粘度的方式排除细菌。STUDY 1A：我们将首先确认我们最初的发现，即木耳在20g菊粉后减少呼气氢反应，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如何，后者也在体温下凝胶。我们将通过给健康志愿者500毫升水和20克菊粉来做到这一点，在其中加入a)木耳b)相当于木耳的纤维素混合物c)等粘度的纤维素，但经修饰形成凝胶或d)单独添加菊粉。我们认为，仅靠高粘度不会产生这种效果，但胶凝会产生这种效果。如果是真的，我们将使用凝胶纤维素进行研究1B，以确定在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在实验室评估不同纤维素制剂对发酵途径的影响。研究3：在我们的实验室模型结肠中，将使用研究1受试者的粪便样本来将产气量与菊粉的其他分解产物(包括SCFAs)关联起来，以了解这些物质如何随产气量的不同而变化。研究4：这些核磁共振研究将测量研究1中最有效的纤维素如何改变菊糖流入结肠和产气。我们还将使用“智能pH药丸”(一种通过肠道发出指示酸度的无线电信号的吞咽药丸)来测量菊糖对结肠中酸度的反应以及纤维素混合物如何改变它。研究5：将使用研究4的结果来准确地模拟我们的结肠模型中的流速、酸度和浓度，并测量由纤维素引起的SCFA产量的变化。研究6：我们将每天给IBS患者服用含有菊粉的纤维素，持续3周，然后使用我们的模型结肠评估气体和结肠容量，以及相关的肠道症状(气体、疼痛、腹胀)和大便发酵途径。如果我们的研究成功，可以很容易地将纤维素添加到现成的食物中，以便在不引起不良症状的情况下食用大分子FODMAP。他们也可以作为一种治疗方法被开出处方。

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.