Understanding the mechanisms for the variation in beneficial effects of dietary fibre in Irritable Bowel Syndrome (IBS): an old concept in new light

了解膳食纤维对肠易激综合症 (IBS) 有益作用变化的机制：新视角下的旧概念

• 批准号: MR/N029097/1
• 负责人: Kevin Whelan
• 金额: $ 51.48万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN029097%2F1
• 关键词: Understanding; mechanisms; variation; beneficial; effects

IBS is a major, growing public health problem affecting 10-15% of adults worldwide. The profound morbidity places a huge financial burden on individuals, the healthcare system and the workplace. For example, Mexicans with IBS on average spend 20% of their income on IBS-related medical expenses, are 50% more likely to report increased medical visits and have a 3-fold greater risk of absenteeism. Pharmaceutical and dietary interventions have some efficacy in IBS, although the latter encourage self-management. More recently dietary management has focussed on dietary restriction (e.g. the low FODMAP diet), but the limitations of these include physiological sequelae (e.g. impaired nutrient intake, altered gut bacteria) as well as the complexity of advice, access to dietitians and comprehensibility (e.g. people with low literacy). Dietary approaches to manage IBS that are easy to implement and inexpensive, therefore widely applicable across socio-economic and ethnic groups are required - a challenge this proposal aims to address. In recent years, our understanding of dietary fibre has progressed considerably uncovering potential therapeutic opportunities applicable in IBS. At present national and international guidelines provide limited and often conflicting recommendations regarding fibre supplementation in IBS. These guidelines are based upon trials of dietary fibre in IBS symptoms that report opposing effects reflecting four key issues that this proposal addresses: (1) variations in the types of fibres used in historic trials, which due to out-dated crude classification of dietary fibre were not supported physiological actions; (2) our limited understanding of the physiological and functional impacts of different fibres specifically in IBS; (3) limited investigation of the physiological effects of novel fibres or the co-administration of different fibres; and (4) variations in the physiology of different sub-types of IBS (i.e. IBS-D, IBS-C). Given these limitations, we believe the therapeutic potential of dietary fibre as a low-cost management strategy is underexploitedIn order to gain a robust understanding of the fibre characteristics that may offer therapeutic benefit for IBS this research will consist of two studies investigating the acute (Study 1) and longer-term (Study 2) physiological and therapeutic effects of fibres in IBS. Study 1 will explore how artificial dietary fibre combinations (resistant starch + psyllium) and naturally occurring combinations (nopal, a native crop to Mexico) (informed by our team of experts in carbohydrate chemistry, gut physiology and gut microbiology) affect gut physiology (e.g. colonic gas production) using non-invasive MRI techniques. This will provide unique insight into underlying mechanisms of action, tolerances and variations in response both between different fibres and within IBS subtypes. These key principles will be used to guide selection of an optimal dietary fibre formulation as well as the most responsive sub-type of IBS to inform a 2-month clinical trial (Study 2). Study 2 will aim to assess the longer-term microbiological and physiological effects of dietary fibre supplementation and whether this translates into symptom relief in IBS. This study will be undertaken in both the UK and Mexico IBS populations exploring specific impacts of the selected fibres on fundamental mechanisms including gut microbiota and gut transit time using the latest sequencing and gastrointestinal motility technology, respectively. In addition, this study will translate several novel mechanisms, based on experimental work, to gain a better understanding of how dietary fibre may exert a benefit. Lastly, study 2 will investigate whether a non-invasive diagnostic model developed by our group can be used to identify IBS patients most likely to respond to dietary fibre, which, if successful will help better characterise the IBS population and pave the way towards personalised treatment plans.

IBS是一个主要的、日益严重的公共卫生问题，影响着全球10%-15%的成年人。这种严重的发病率给个人、医疗保健系统和工作场所带来了巨大的经济负担。例如，患有IBS的墨西哥人平均将收入的20%花在与IBS相关的医疗费用上，报告就诊次数增加的可能性高出50%，旷工风险高出3倍。药物和饮食干预对IBS有一定的疗效，尽管后者鼓励自我管理。最近的饮食管理侧重于饮食限制(例如低FODMAP饮食)，但这些限制包括生理后遗症(例如营养摄入受损、肠道细菌改变)以及建议的复杂性、获得营养师的机会和可理解性(例如识字率低的人)。管理IBS的饮食方法需要易于实施和廉价，因此在社会经济和种族群体中广泛适用--这是本提案旨在解决的一个挑战。近年来，我们对膳食纤维的了解有了很大的进步，发现了适用于IBS的潜在治疗机会。目前，国家和国际指南对IBS的纤维补充提供了有限且往往相互矛盾的建议。这些指南基于膳食纤维在IBS症状中的试验，这些试验报告了相反的效果，反映了这项建议解决的四个关键问题：(1)在历史性试验中使用的纤维类型的差异，这是由于膳食纤维的原始分类过时而没有得到生理作用的支持；(2)我们对特定于IBS的不同纤维的生理和功能影响的了解有限；(3)对新型纤维的生理影响或不同纤维联合使用的研究有限；以及(4)不同类型的IBS(即IBS-D、IBS-C)的生理学差异。鉴于这些局限性，我们认为膳食纤维作为一种低成本管理策略的治疗潜力尚未得到充分开发。为了更好地了解可能为IBS提供治疗益处的纤维特性，本研究将包括两项研究，调查纤维在IBS中的急性(研究1)和长期(研究2)生理和治疗效果。研究1将探索人工膳食纤维组合(抗性淀粉+木耳)和天然组合(墨西哥原产作物nopal)(由我们的碳水化合物化学、肠道生理学和肠道微生物学专家团队提供信息)如何使用非侵入性MRI技术影响肠道生理(例如结肠气体产生)。这将为不同纤维之间和IBS亚型之间的潜在作用机制、耐受性和反应差异提供独特的见解。这些关键原则将用于指导最佳膳食纤维配方的选择以及最敏感的IBS亚型，以指导为期2个月的临床试验(研究2)。研究2旨在评估补充膳食纤维的长期微生物学和生理学影响，以及这是否转化为IBS症状的缓解。这项研究将在英国和墨西哥的IBS人群中进行，分别使用最新的测序和胃肠动力技术探索选定纤维对肠道微生物区系和肠道转运时间等基本机制的具体影响。此外，这项研究将在实验工作的基础上翻译几种新的机制，以更好地了解膳食纤维如何发挥益处。最后，研究2将调查我们小组开发的非侵入性诊断模型是否可以用于识别最有可能对膳食纤维有反应的IBS患者，如果成功，这将有助于更好地描述IBS人群的特征，并为个性化治疗计划铺平道路。

项目成果

Varying effects of bran, psyllium and prickly pear cactus fibre (nopal) on small intestinal water content and colonic volume demonstrated using magnetic resonance imaging

使用磁共振成像证明麸皮、洋车前子和仙人掌纤维（胭脂）对小肠含水量和结肠体积的不同影响

• 发表时间: 2018
• 作者: Gunn D

Mo1551 PSYLLIUM REDUCES COLONIC HYDROGEN PRODUCTION FOLLOWING INGESTION OF INULIN IN IRRITABLE BOWEL SYNDROME

Mo1551 洋车前子可减少肠易激综合征患者摄入菊粉后结肠氢的产生

• DOI: 10.1016/s0016-5085(20)32917-6
• 发表时间: 2020
• 期刊: Gastroenterology
• 影响因子: 29.4
• 作者: Gunn D

Effect of Consumption of Nopal Fiber (Opuntia Ficus Indica) Over the Secretion of Gastrointestinal Hormones in Patients with Irritable Bowel Syndrome.

食用胭脂纤维（仙人掌）对肠易激综合征患者胃肠激素分泌的影响。

• 发表时间: 2019
• 作者: M. Amieva-Balmori, HA.

Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies.

• DOI: 10.1136/gutjnl-2021-324784
• 发表时间: 2022-05
• 期刊: Gut
• 影响因子: 24.5
• 作者: Gunn D;Abbas Z;Harris HC;Major G;Hoad C;Gowland P;Marciani L;Gill SK;Warren FJ;Rossi M;Remes-Troche JM;Whelan K;Spiller RC
• 通讯作者: Spiller RC

El consumo de fibra de nopal (opuntia ficus- Indica) en polvo mejora los síntomas en pacientes con síndrome de intestino Irritable. Resultados de un ensayo clínico Aleatorizado y controlado con placebo, durante 7 días.

El consumo de fibra de nopal (opuntia ficus- Indica) en polvo mejora los síntomas en pacientes con síndrome de intestino 易激惹。

• 发表时间: 2017
• 作者: H Taboada-Liceaga