The Roadmap to FODMAP

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Mavis Lindsey
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1 The Roadmap to FODMAP Food Intolerance and Sugar Malabsorption in Chronic Abdominal Pain Food The Good the Bad and the Ugly April 2017 Pediatrics

2 Disclosure I have the following financial relationships to disclose: Mead Johnson Nutrition (consultant) Products or services provided by this company may be relevant to this presentation.

3 Objectives 1) Review the perspectives of our patients re: food in children with chronic abdominal pain 2) Review the pathogenesis of fermentable carbohydrates 3) Review the evidence of a low fermentable substrate diet

4 Diet Inflammation Microbiome Psychosocial factors Chronic Abdominal Pain Visceral hypersensitivity Genetics

5 Diet in IBS: The Perspective From Our Patients Irritable bowel syndrome (IBS) is the most common type of chronic abdominal pain Affecting up to 20% of school-children Food is perceived to be a culprit in the majority of those with IBS Adults (84%) 1 Children (93%) 2 Children with IBS identify more problem foods and avoid more foods than healthy children 2 1 Bohn L et al. Am J Gastroneterol 2013; 108(5): Chumpitazi BP et al. J Acad Nutr Diet 2016; 116(9):

6 Diet in IBS: The Perspective From Our Patients Chumpitazi BP et al. J Acad Nutr Diet 2016; 116(9):

7 Diet in IBS: The Perspective From Our Patients Chumpitazi BP et al. J Acad Nutr Diet 2016; 116(9):

8 Diet in IBS: The Perspective From Our Patients Chumpitazi BP et al. J Acad Nutr Diet 2016; 116(9):

9 Diet in Functional Abdominal Pain: The Perspective From Our Patients I don t eat at friends houses; I don t trust her food. I bring my own. -13 yo F with functional GI disorder You kind of feel left out because you want to be able to eat the same things they do, but don t want to be that person at the party throwing up because of that. -16 yo F with functional GI disorder Carlson MJ et al. J Acad Nutr Diet 2014; 114:

10 Diet in IBS: The Prospective From Our Patients Chumpitazi BP et al. J Acad Nutr Diet 2016; 116(9):

11 Objectives 1) Review the perspectives of our patients re: food in children with chronic abdominal pain 2) Review the pathogenesis of fermentable carbohydrates 3) Review the evidence of a low fermentable substrate diet

12 Adverse Reactions to Food Adverse Reaction to Food Non Toxic Toxic Ortolani C et al. Best Pract Res Clin Gastroenterol 2006; 20(3):

13 Adverse Reactions to Food Adverse Reaction to Food Non Toxic Toxic Toxins Saxitoxin (shellfish) Vasoactive amines Histamine (spoiled fish) Ortolani C et al. Best Pract Res Clin Gastroenterol 2006; 20(3):

14 Adverse Reactions to Food Adverse Reaction to Food Non Toxic Toxic Non Immunologic Immunologic Ortolani C et al. Best Pract Res Clin Gastroenterol 2006; 20(3):

15 Adverse Reactions to Food Adverse Reaction to Food Non Toxic Toxic Non Immunologic Immunologic Food allergy IgE mediated (wheat allergy) Non-IgE mediated (celiac disease)? Nonceliac Gluten sensitivity Ortolani C et al. Best Pract Res Clin Gastroenterol 2006; 20(3):

16 Adverse Reactions to Food Adverse Reaction to Food Non Toxic Toxic Non Immunologic Immunologic Food Intolerance Ortolani C et al. Best Pract Res Clin Gastroenterol 2006; 20(3):

17 Fermentable (bacterial metabolism) Oligosaccharides (fructans/galactans) Disaccharides (lactose) Monosaccharides (fructose) And FODMAP Carbohydrates Polyols (sugar alcohols - sorbitol) Poorly absorbed, osmotically active, rapidly fermented (produce gas) Barrett J, et al. Pract Gastroenterol 2007;31:51-65

18 FODMAP Hypothesis Malabsorbed dietary carbohydrates Physiologic effects Osmotic load Luminal fluid Fermentable substrate Gas production Other effects? Luminal distention Symptoms Diarrhea Bloating Pain Gas Barrett J, et al. Pract Gastroenterol 2007;31:51-65

19 FODMAP Pathogenesis Poorly Absorbed - Fructose Biesiekierski JR. United European Gastrenterol J. 2014;2(1):10-13

20 FODMAP Pathogenesis: Genetics Poorly Absorbed - Lactose Curry A Nature 2013;500:20-22

21 FODMAP Pathogenesis: Genetics Genetics of Lactase Expression Campbell AK et al. Sci Prog 2009;92:241

22 FODMAP Pathogenesis: Genetics Genetics of Lactase Expression Baffour-Awuah NY et al. J Pediatr Gastroenterol Nutr 2015; 60:182

23 Poorly absorbed FODMAP Pathogenesis Fructans/Galactans Wheat/Onions Legumes Fructose/Galactose polymers Lack human hydrolases Essentially intact into colon Sugar alcohols Sorbitol, Xylitol, Mannitol Passive absorption Sonnenburg ED, et al. Cell 2010;141:1241

24 FODMAP Pathogenesis Osmotically active - Fructose Murray K et al. Am J Gastroenterol 2014;109:110-9

25 Small Bowel Water Content (ml) FODMAP Pathogenesis Osmotically active - Fructose Murray K et al. Am J Gastroenterol 2014;109:110-9

26 Osmotically active FODMAP Pathogenesis Mannitol increases small bowel water content 10x versus glucose in healthy volunteers 1 Dietary FODMAP content correlates with ileostomy output 2 Higher output with higher FODMAP content Enteral formulas with lower FODMAP content cause less enteral nutrition-associated diarrhea 3 1 Marciani L et al. Gastroenterology 2010;138: Barret JS et al. Aliment Pharmacol Ther 2010;31: Halmos EP J Gastroenterol Hepatol 2013;28(Suppl4):25-28

27 FODMAP Pathogenesis Highly Fermentable Murray K et al. Am J Gastroenterol 2014;109:110-9

28 FODMAP Pathogenesis Highly Fermentable Murray K et al. Am J Gastroenterol 2014;109:110-9

29 FODMAP Pathogenesis Differences between IBS vs. Healthy Controls IBS/High FODMAP Healthy/High FODMAP IBS/Low FODMAP Healthy/Low FODMAP Ong DK et al. J Gastroenterol Hepatol 2010;25:

30 Gut Microbiome differs between IBS and Healthy Controls Rajilic-Stojanovic M, et al. Am J Gastroenterol 2015; 110:

31 FODMAP Pathogenesis Low FODMAP diet efficacy 25% subjects do not improve Microbiome Composition Changes Low FODMAP diet reduces luminal Bifidobacteria 1 Decreased relative abundance Clostridium cluster XIVa, Akkermansia muciniphila, Ruminococcus 2 Low FODMAP diet vs. habitual diet in children 3 Responders with different baseline composition 1 Staudacher HM et al. J Nutr 2012;142: Halmos EP et al. Gut 2015;64(1): Chumpitazi BP et al. Gut Microbes 2014;5:1-11

32 FODMAP Pathogenesis: Responders and Baseline Microbiome Composition OTU Taxonomy LDA (Log 10) P-value Bacteroides (genus) Ruminococcaceae (family) Faecalibacterium prausnitzii (species) Ruminococcaceae (family) Bacteroides (genus) Bacteroides (genus) Bacteroides (genus) Dorea (genus) Bacteroides (genus) Clostridiales (order) Bacteroides, Ruminococcaceae, F. prausnitzii, Dorea with high saccharolytic potential Chumpitazi BP et al. Aliment Pharmacol Ther 2015; 42(4):

33 FODMAP Pathogenesis: Responders and Microbial Metabolic Potential KO Pathway LDA (Log 10) P-value KO2529 LacI family transcriptional regulator KO1209 Alpha-N-arabinofuranosidase KO3496 Chromosome partitioning protein LacI family transcriptional regulator Regulate carbohydrate utilization genes Allow expression of genes with substrate/environment changes Alpha-N-arabinofuranosidase Arabinogalactans: galactans found in wheat flour Chumpitazi BP et al. Aliment Pharmacol Ther 2015; 42(4):

34 FODMAP Pathogenesis: Nonresponders and Baseline Microbiome Composition OTU Taxonomy LDA (Log 10) P-value Bacteroides (genus) Turicibacter (genus) Clostridialies (order) Turicibacter (genus) Uniquely enriched in Turicibacter Fermentatative capacity for grains given to animals Decreased fructo-oligosaccharide fermentation capacity T. sanguinis with limited carbohydrate capacity Enriched in bacteria unable to ferment FODMAPs Chumpitazi BP et al. Aliment Pharmacol Ther 2015; 42(4):

35 Objectives 1) Review the perspectives of our patients re: food in children with chronic abdominal pain 2) Review the pathogenesis of fermentable carbohydrates 3) Review the evidence of a low fermentable substrate diet

36 FODMAP Summary Evidence Review Adult Irritable Bowel Syndrome (IBS) 1 Double Blind Placebo Controlled Challenge Study 4 Randomized Controlled Trials Several uncontrolled studies (symptom improvement 56-94%) Pediatric IBS One uncontrolled study (n=8, symptom improvement 50%) 1 Randomized Cross-Over Trial Inflammatory Bowel Disease Open-label studies

Symptom Severity FODMAP Evidence Review Adult IBS Double Blind Challenge Study 80 60 40 20

37 Symptom Severity FODMAP Evidence Review Adult IBS Double Blind Challenge Study Fructose Fructan Mix Glucose Shepherd SJ et al. Clin Gastroenterol Hepatol 2008;6:765-71

38 FODMAP Evidence Review Adult IBS Randomized Crossover Trial (n=30) Halmos EP et al. Gastroenterology 2014;146:67-75

39 FODMAP Evidence Review Healthy adults Randomized Crossover Trial (n=8) Halmos EP et al. Gastroenterology 2014;146:67-75

40 FODMAP Evidence Review Healthy Adults Randomized Controlled Trial (n=37) McIntosh K et al. Gut 2016;Mar 14 [Epub]

41 FODMAP Evidence Review Pediatric IBS Randomized Crossover Trial (n=33) 48 hour interventions; TACD=Typical American Childhood Diet Chumpitazi BP et al. Aliment Pharm Ther 2015;42:418-27

42 Take Home Points Diet related symptom generation is commonly perceived in children with IBS FODMAP carbohydrates represents a nonimmunologic adverse food reaction Gas production Osmotic load play a role with FODMAPs Microbiome composition and host factors are being elucidated Evidence is growing supporting the use of a low FODMAP diet in children with IBS

Children s Nutrition Research Center Robert Shulman Danita Czyzewski Mariella Self Erica Weidler Ann McMeans Adetola Vaughan TCH GI Section and Motility Program Acknowledgements Texas Children s

43 Children s Nutrition Research Center Robert Shulman Danita Czyzewski Mariella Self Erica Weidler Ann McMeans Adetola Vaughan TCH GI Section and Motility Program Acknowledgements Texas Children s Microbiome Center James Versalovic Emily Hollister Julia Cope Support NASPGHAN Foundation Texas Medical Center DDC (NIH DK56338) NIDDK (K23 DK101688) Pediatrics Page 42 xxx00.#####.ppt 4/11/2017 5:38:24 PM

FODMAPs: Major role in food sensitivities

FODMAPs: Major role in food sensitivities : 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