: Major role in food sensitivities Jessica Biesiekierski Post-doctoral Research Fellow Translational Research Center for Gastrointestinal Disorders KU Leuven, Belgium Role of food in GI symptoms? Abdominal pain, bloating, and altered bowel habits common in gastrointestinal disorders IBS, IBD, coeliac disease Luminal distension plays a key role Degree of bowel distension dictated by luminal volume (solid, gas and fluid components) Therefore, targets for therapy are dietary carbohydrates that are: poorly absorbed rapidly fermented osmotically active Development of the hypothesis - Restriction of lactose in hypolactasia Haemmerli et al 1965 Am J Med - Fructose malabsorption and restriction studies Andersson & Nygren1978; Rumessen & Gudman Hoyer 1986 Fruct oligosaccharides & galacto ligosaccharides Disaccharides Lactose (lactulose)
Disaccharides Monosaccharides Free Fructose (fructose in excess of glucose) Disaccharides Monosaccharides And Polyols Sorbitol, mannitol Current evidence 2 retrospective telephone questionnaires Shepherd et al 26 AU; Gearry et al 29 AU 1 prospective symptom questionnaire De Roest et al 213 NZ 4 randomized controlled trials: 1 rechallenge of fructose and fructans Shepherd et al 28 AU 2 crossover single blinded interventions (low vs high) Barrett et al 21 AU; Ong et al 21 AU (low vs habitual) Staudacher et al 212 UK 1 crossover single blinded feeding trial (low vs Aust.) Halmos et al 214 AU 1 non-randomized comparative study (low vs NICE) Staudacher et al 211 UK Study- Digestion and fermentation of : A study in volunteers with an ileostomy 1 volunteers with end-ileostomy Mean age 55 years (31-78), 4 male 8 Ulcerative colitis, 2 Crohn s disease Protocol Protocol Diet 1 Washout period 2 weeks Diet 2 Diet 1 Washout period 2 weeks Diet 2 DIETS High vs Low Randomised, cross over Single blinded All food provided 24 hour effluent collection Visual Analogue Scale (perception of output, symptoms)
Total daytime output Effluent composition 1 p=.1 75 Water content p=.1 3 Dry weight p=.3 Total output (g) 75 5 25 High 22% Low Water content (g) 5 25 High Low 2% Dry weight (g) 2 1 High Low 24% Study - Breath hydrogen and abdominal symptom production in volunteers consuming foods either low or high in Study Protocol 7 day washout Randomized, single blinded, crossover intervention study Baseline Low diet High diet Subjects: 15 IBS (Rome III) 15 Healthy volunteers - no GI symptoms Symptom diary Hourly breath collection (13 h) Symptom diary Hourly breath collection (13 h) Ong et al, J Clin Gastro 21 Ong et al, J Clin Gastro 21 Influence of intake on breath hydrogen production Low 23g/day High 85g/day Abdominal pain Healthy controls IBS p<.5 Mann-Whitney U & Wilcoxon signed ranks tests Onget al, J ClinGastro 21 Onget al, J ClinGastro 21
Large intestine Randomised, controlled, single-blind, crossover trial of 3 patients with IBS and 8 HV Small intestine content: Low 3.5 g/day Typical Aust 23.7 g/day water delivery gas production Luminal distension Altered motility Pain, bloating, distension, wind, constipation +/- diarrhoea Dept Gastro. CCS, Monash University Halmos et al, Gastroenterol 214 5-day faecal collections: Low Higher faecal ph Greater microbial diversity Reduced total bacterial abundance Reduced Clostridium coccoides Increased Ruminococcus torques n=22 n=19 Staudacher et al, J Nutr 212 Implementation 1. Dietitian-delivered diet Education on principles Information on food composition Ways of choosing foods, cooking, recipes... E.g., Double soaking legumes Lactase enzyme supplementation 2. Strict for 2-6 weeks If efficacious, rechallenge & loosen diet according to tolerance If adherent and no response in 4 weeks, abandon diet Murray et al, Am J Gastroenterol 214
: absorption patterns content of cereal products per serve POORLY ABSORBED IN ALL Always fermented in colon, so a : fructo- certain (FOS) amount & galacto- will result (GOS) in > No small intestinal hydrolases symptoms SLOWLY ABSORBED IN ALL Free fructose (i.e., fructose in excess of glucose) Polyols: sorbitol, mannitol... Absorptive capacities will vary in > Proportion passively individuals, absorbed so (~3%) symptoms will also vary. Breath testing may be useful. POORLY ABSORBED IN ONLY SOME Lactose 1-95% depending upon ethnicity, other factors Biesiekierski et al, J Human Nutr Dietetics 211 content of cereal products per serve GFD versus low?? Gluten-free products Biesiekierski et al, J Human Nutr Dietetics 211 Protocol: Run-in phase Protocol: Intervention phase All food provided during the interventions Low, gluten free diet BASELINE Education low diet 1 RUN IN HIGH GLUTEN >14 day washout >14 day washout LOW GLUTEN PLACEBO Usual GFD Usual GFD + Low in 16 g wheatgluten daily 2 g wheatgluten daily + 14 g highlydigestable whey protein daily 16 g highlydigestable whey protein daily Biesiekierski et al, Gastroenterol 213 Biesiekierski et al, Gastroenterol 213
Results (n=37) Effect of low diet Overall Symptoms Results Effect of treatment periods VAS (-1mm) 6 4 2 Baseline P<.1 Run-in VAS symptom severity score: =none 1=worst VAS (1-1mm) 25 2 15 1 5 OVERALL SYMPTOMS Repeated measures ANOVA p=ns Day 1 2 3 4 5 6 7 VAS symptom severity score: =none 1=worst High Gluten Low Gluten Placebo (whey) p<.1 Biesiekierski et al, Gastroenterol 213 Biesiekierski et al, Gastroenterol 213 content of cereal products per serve Gluten-free products Low grains suitable for people with IBS Biesiekierski et al, J Human Nutr Dietetics 211 Long term use of low diet Potential consequences: Effects on gut microbiota Effects on dietary fibre intake Nutritional adequacy Other clinical applications: Other disease states e.g., IBD or treated coeliac disease with functional GI symptoms Gearry et al 29 J Crohns Colitis Other unanswered questions: Predictors of response Comparison with alternative strategies Thank you Program of measurement of food content using a combination of HPLC and enzymatic assays Muir et al JAFC 28, 29; Biesiekierski et al JHND 211; Yao et al JHND 213 http://www.med.monash.edu/cecs/gastro/fodmap/