Adjunct therapies to the low FODMAP dietary management of irritable bowel syndrome

Functional bowel disorders (FBD) including irritable bowel syndrome (IBS) are characterised by abdominal pain, bloating and altered bowel habits, and contribute to reduced quality of life and socioeconomic burden. The low FODMAP (fermentable, oligo-, di-, mono-saccharides and polyols) diet has high-quality evidence for efficacy in reducing symptoms of IBS. Although strict adherence is not intended for the long-term, concern has been raised for the safety of the diet due to potential to cause alterations to the colonic microbiota, and to reduce nutritional adequacy and fibre intake. Of particular concern are vegetarians requiring the low FODMAP diet due to limited protein sources. Hence, adjunct therapies to the low FODMAP diet to reduce the dietary restrictions are welcomed.
   
   This thesis contains a series of experiments which aimed to 1) determine if glucose addition to excess fructose reduces symptoms in FBD fructose malabsorbers; 2) evaluate the FODMAP content of a range of vegetarian foods, focusing on the effect of food processing; 3) assess if oral α-galactosidase reduces symptoms in IBS when targeted to a high galacto-oligosaccharide (GOS) diet; 4) assess the effects of oral fructanase alone and in combination with α-galactosidase on the fructan and GOS content of ileal digesta from pigs following consumption of a high fructan and GOS diet.
   
   Adjunct therapies were assessed in two randomised, placebo-controlled, cross-over trials. In 26 FBD participants, addition of glucose to excess fructose was unable to reduce symptoms despite causing reductions in breath hydrogen. In 31 IBS participants, α-galactosidase reduced symptoms in GOS sensitive individuals. However, the proposed mechanism of α-galactosidase action, reduction of colonic fermentation, was not supported as breath hydrogen production was unchanged.
   
   Carbohydrate analysis of 37 vegetarian and 14 processed foods has expanded the FODMAP food composition database. Of the food processing techniques analysed, pickling provided the greatest reduction in FODMAP content. Canned legumes have substantially lower FODMAP content compared to dried varieties. Additionally, cooking red-kidney-beans for longer lengths of time lowered the FODMAP composition.
   
   The concept of enzyme therapy to reduce the effects of FODMAPs was extended to the use of fructanase (not currently approved for human use) to target fructans in vitro and in vivo. Using a pig ileostomy model, fructanase provided fructan digestion within the small intestine. However, combining fructanase and α-galactosidase was not additive in reducing total FODMAP content of ileal digesta.
   
   In conclusion, numerous adjunct therapies to reduce food-related symptoms in patients with FBD can now be implemented into practice. Orally-administered α-galactosidase can be utilised in GOS-sensitive individuals, and alterations to cooking methods and use of food processing techniques will likely improve patient tolerance, particularly for vegetarian protein sources. However, glucose addition to excess fructose is not effective. The use of fructanase has been supported and now requires safety evaluation and subsequent clinical trial. Further work is required to understand the mechanism of α-galactosidase and why it does not appear to have additive effects with fructanase. Current and promising tools to reduce the burden of food restriction in those requiring a low FODMAP diet have, therefore, been defined.