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. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.