From Restriction to Modulation: Gel-Forming Fibres as a Novel Approach to Modulate FODMAP Fermentation in Irritable Bowel Syndrome

Abstract

Background: Irritable bowel syndrome (IBS) impacts approximately 10% of the global population. Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) induce symptoms through rapid colonic fermentation and gas generation. Although the low-FODMAP diet effectively relieves symptoms, it presents several challenges, including nutritional deficiencies, reduced beneficial gut microbiota, and poor adherence to the diet. Co-administration of gel-forming fibres with FODMAPs offers a promising alternative strategy that may preserve beneficial fermentation while reducing gas production that triggers symptoms. Aims: This thesis aimed to understand the mechanism of reduction in gas production observed when combining psyllium with inulin, and to investigate whether methylcellulose could serve as a potential alternative to psyllium for reducing gas production in healthy participants, utilising hydrogen breath testing as the main assessment method. The core hypothesis of this thesis was that the gel-forming dietary fibres slow the rate of colonic hydrogen production from fermentable substrates, potentially through mechanisms that alter substrate accessibility for the colonic microbiota, and redistribute fermentation activity beyond the proximal colon. Methods: Four complementary studies were conducted using randomised, controlled, single-blind, crossover designs involving healthy adults (n=84). These included: (1) in-vitro rheological characterisation of methylcellulose formulations and a pilot in-vivo study aimed to test the hypothesis that methylcellulose would reduce breath hydrogen production similarly to psyllium (COCOA1, n=15); (2) a mechanistic investigation aimed to test the hypothesis that psyllium's inhibition of colonic gas production was due to its high viscosity slowing the delivery of inulin to the colon, using divided dose inulin delivery to mimic psyllium's slowed substrate delivery (EON, n=17); (3) a study aimed to test the hypothesis that 2 reformulated methylcellulose is non-inferior to psyllium in reducing breath hydrogen production compared to control (COCOA2, n=30); and (4) a study aimed to test the hypothesis that a gel of either methylcellulose or psyllium incorporating inulin would reduce colonic gas volumes assessed by magnetic resonance imaging (MRI) 0-6h and 24h post-ingestion compared to inulin combined with a control. This chapter presents transit data, particularly orocaecal transit time (OCTT) measured by magnetic resonance imaging (MRI) and compared with OCTT evaluated by breath test (RUFUS, n=22). Results: Psyllium consistently reduced early-phase (0-6 hours) breath hydrogen production when co-administered with inulin across all studies, confirming previous findings. Mechanistic study revealed that psyllium's effects extended beyond simple transit delay, as divided-dose inulin delivery decreased early hydrogen but increased overall 24-hour hydrogen production. The reformulated methylcellulose demonstrated non-inferiority to psyllium in reducing 6-hour hydrogen production. Both fibres primarily redistributed fermentation temporally and spatially rather than inhibiting total fermentation, with 24-hour cumulative hydrogen production showing minimal differences between interventions. MRI validation confirmed that both fibres delayed fermentation onset relative to their physical arrival at the caecum, with psyllium showing superior distal fermentation. Conclusions: Gel-forming fibres effectively modulate FODMAP fermentation patterns by redistributing gas production from the proximal to the distal colon, while maintaining beneficial fermentation effects. This approach represents a paradigm shift from restriction-based to modulation-based IBS management, potentially allowing patients to maintain dietary variety while managing symptoms. These mechanistic insights provide a foundation for the development of fibre-based interventions as alternatives to restrictive low-FODMAP diets in clinical practice.