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

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 underexploited

In 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.

SOCIETAL:IBS is a major, growing public health problem affecting 10-15% of adults worldwide, with even higher prevalence reported in Mexico (16-33%). The morbidity associated with the disease is significant. In fact, IBS is associated with a lower health related QOL than kidney disease and diabetes. Moreover, a study undertaken in almost 2000 people with IBS reported participants would trade 15years of their lifespan to receive a treatment that would make them symptom free. Pharmaceutical and dietary interventions have some efficacy in IBS, although the latter are cheaper and encourage self-management. However, there are several shortcomings of current approaches including the complexity of some dietary restrictions, access to qualified dietitians, and suitability for ethnic minority groups. Dietary approaches to manage IBS that are easy to implement and inexpensive, therefore widely applicable across socio-economic and ethnic groups are required - an outcome this proposal aims to achieve to enhance the welfare of society.
In addition, this proposal is also likely to promote social cohesion particularly in Mexico where nopal is not only one of the largest crops of small and medium markets, but forms part of the Mexican Coat of Arms. Therefore the ownership of this research combined with the potential growth of the nopal industry (which will help job creation and income diversification - both key drivers of community development) highlights how this proposal will further benefit the community.
ECONOMIC:IBS has a considerable impact on direct and indirect healthcare costs. Within the UK, direct health care costs have been estimated up to US$2000 annually per IBS patient.4 Indirect costs of the condition are also extensive with patients taking up to 21 days off work annually for their condition. Total NHS annual expenditure on IBS in the UK was estimated at £45.6 million in 1995, equivalent to 0.1% of the total NHS spend. Given the increased prevalence and awareness of IBS these figures are thought to grossly underestimate current costs. Similarly in Mexico the cost of IBS is substantial, however, in contrast more than 50% of healthcare costs are covered by individuals. A study conducted by Dr Remes-Troche (Mexico PI) identified the alarming economic burden of IBS on the individual with the average patient spending 20% of their income on medical expenses related to IBS.5 Therefore a low cost therapy such as dietary fibre, which for many Mexicans can be sourced from their own garden, will be associated with significant cost savings for 1) Health care systems; (2) Employees and (3) Individuals suffering with IBS.
This proposal has significant economic potential for the Mexican agricultural industry. If our hypothesis is correct and nopal has a therapeutic benefit in IBS this will add great value to the nopal industry to which Mexican leads internationally. In fact, a review of the status of the nopal industry, commissioned by the Food and Agriculture organisation (FAO), identified the lack of scientific support for the health benefits of nopal as a key limitation to international market penetration.6 Furthermore, the mechanistic work from this research is likely to stimulate research into the use of nopal for other conditions, broadening the scope for economic growth.
ACADEMIC: This proposal includes a number of training and upskilling opportunities for clinicians using new and innovative approaches. This will include formalised training for Mexican MR clinician Dr Gill-Valadez (Mexico Co-I) and a radiologist technician in the MR protocols for measuring novel markers of gut physiology and functionality developed by our UK team. In addition, clinicians from the UK and Mexico will be trained by company representatives in cutting-edge software data analysis. Moreover, our engagement with commercial companies,enhance the knowledge economy by establishing the efficacy of these products and devices, already on the market, in IBS.