Dietary FODMAPs and the pathogenesis of gastrointestinal symptoms

A low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols) diet is often used to manage functional gastrointestinal symptoms seen in patients with irritable bowel syndrome (IBS) and Crohn’s disease, yet evidence of its efficacy is limited. Additionally, given FODMAPs are prebiotics and their fermentation by colonic microbiota produces short-chain fatty acids (SCFA) with putative health benefits, reducing FODMAP intake may have adverse effects on colonic health. Furthermore, the role of FODMAPs in functional gastrointestinal symptoms commonly seen in patients receiving enteral nutrition (EN) is unexplored. A series of studies were undertaken to 1) fill gaps in evidence regarding effects of the low FODMAP diet on gastrointestinal symptoms compared to the moderate FODMAP intake of a typical Australian diet in unselected IBS patients; 2) compare the effects of these two diets on faecal biomarkers related to colonic health; 3) examine clinical predictors of functional gastrointestinal symptoms in patients receiving EN, with specific attention to enteral formula composition; and 4) evaluate the FODMAP content of enteral formulas by applying methodologies validated for food with additional controls to determine accuracy. From the results of the single-blinded, randomised, controlled, cross-over trial, mean daily gastrointestinal symptoms were halved in 30 IBS subjects receiving 21-days of low FODMAP compared to typical Australian diet. Similar patterns were seen in nine quiescent Crohn’s disease subjects and symptoms were minimal and unaltered by diet among eight healthy controls. Faecal samples collected from days 17-21 of the diets showed marked reduction in abundance of bacteria with prebiotic effects, but no observed changes in SCFA. From a retrospective study of 160 patients receiving EN, multivariate analysis showed a fivefold reduction in risk of developing diarrhoea in patients receiving the formula Isosource® 1.5 compared to other formulas. The FODMAP content of Isosource® 1.5 was substantially lower than the other formulas when assess by standard methodologies, but additional controls suggested that constituents of enteral formulas artefactually influence these methodologies. This was substantiated by an in vivo challenge of 15 breath-hydrogen-producing volunteers ingesting bolus doses of Isosource® 1.5 and another formula of seemingly higher FODMAP content in a cross-over study design. No increased breath hydrogen levels were seen after ingestion of the formulas compare to the positive control lactulose. This thesis provides high-quality evidence supporting use of the low FODMAP diet as therapy for functional gastrointestinal symptoms seen in IBS and Crohn’s disease, however, the diet alters several faecal indices putatively associated with colonic health. The implications of the low FODMAP diet to colonic health require elucidation, but caution should be exercised in recommending the treatment long term. Findings from this thesis also suggest a reduced likelihood of developing diarrhoea in patients receiving Isosource® 1.5 over other formulas. The protective characteristic of Isosource® 1.5 is not the lower FODMAP content as additional controls applied to standard FODMAP analysis methodologies confirm that the analysed formulas are similarly low FODMAP. Further investigation into the cause and effect of increased risk of functional gastrointestinal symptoms seen in EN and the role of Isosource® 1.5 is needed.