Diet s Role in IBD David Suskind M.D. Professor of Pediatrics Director of Clinical Gastroenterology Division of Gastroenterology University of Washington Seattle Children s Hospital
Issues at Hand Inflammatory Bowel Disease Paradigm Fecal microbiome i.e. bacteria in poop Immune system Diet changes the fecal microbiome Immune homeostasis Experience with diet in IBD What is the best Diet for IBD?
Intestinal Health Lining of the Gut Community of Bacteria Microbiome MUCOSAL INTEGRITY Immune System Body s Defense System Vindigni, S Ther Adv Gastroenter 2016 9(4):606-25
Importance of focusing on the environment/microbiome Bach, New England J Med 2002;347:911-20
Fecal Microbiome 100 trillion microorganisms Human gut - 2lbs of bacteria Outnumber human cells by a factor of ten Genomes encode around 3 million different genes 99% 10% 1% Weight Cells Genes Microbiome Human Adapted from Chris Damman MD
Fecal microbiome Who s there? What are they doing? Who s they are varies: microbiota is plastic and personalized. What they re doing is adapting: you, your body, and your environment. Savage, DC. Annu Rev Microbiol 1977; 31:107-133 Backhed, F,et al Science. 2005; 307: 1915-1920. 6
Valm et al, PNAS 2011
Keeping things in Check Protective Coating Physiochemical barrier composed of a thick mucus layer Secondary defense tight junctions Bactericidal proteins Immune Cells
IBD paradigm: Immune dysregulation HEALTH Disease Risk Factors Genetic Antibiotics Western Diet IBD Microbiome MUCOSAL INTEGRITY DYSBIOSIS MUCOSAL DISRUPTION Immune System INFLAMMATION Vindigni, S Ther Adv Gastroenter 2016 9(4):606-25
Animal Model of Diet and Microbiome E. coli R. gnavus F. prausnitzii B. fragilis C. difficile B.stercoris S. cerevisiae
How does diet change the Microbiome Diet effect on the fecal microbiota of five strains of IBD mice mice deficient for genes relevant to host-microbial interactions High fat, high sugar diet vs Low fat high fiber Carmody, R, et al Cell Host & Microbe 2015, (17), 72-84
Diet Rapidly and reproducibly alters human gut microbiome David, L, et al Nature 2014; 505 (7484): 559-563
Western diet increases Bad Bacteria with increased E. coli in CEABAC10 mice Martinez-Medina M, et al Gut 2014;63:116-124
Food Additives: Additional Culprits Maltodextrin: Intestinal defense Processed starch 60% of all packaged items Nickerson, K. et al Gut Microbes 6:1, 78-83. Nickerson, K, et al PLoS One 2012/2014
More Dietary Emulsifiers: CMC and Polysorbate 80 Chassaing B, et al. Nature 519,92-96(2015)
Dietary emulsifiers promote colitis in susceptible mice Chassaing B, et al. Nature 519,92-96(2015)
Clinical Evidence?!?
Exclusive Enteral Nutrition (EEN) Mainstay of nutritional therapy in Crohn s disease 8-12 weeks of exclusive formula No other foods or drinks Oral or via nasogastric tube Meta analysis: enteral nutrition in active Crohn s disease in children Alimentary Pharmacology & Therapeutics 26(6): 795-806, 2007
Specific Carbohydrate Diet (SCD) Sidney Haas MD Early 1930s used to treat celiac disease Popularized by Elaine Gottschall Seattle Children s retrospective study Children with Active Crohn s disease Trialed dietary therapies as sole medical treatment for their Crohn s disease Haas, S, Am J Gastroenterol 1955 Apr;23(4):344-60 Suskind DL, et al, JPGN. 2014 Jan;58(1):87-91.
SCD Studies Study Type of study Pediatric/Adult Number of subjects Findings Suskind DL, et al J Pediatr Gastroenterol Nutr. (2014) * Retrospective case series Pediatric Crohn s disease 7 Normalized labs and induced clinical remission Cohen et al. JPGN (2014) Prospective case series Pediatric Crohn s disease 10 Clinical and mucosal improvements were seen in children with CD Kakodkar S et al. J Acad Nutr Diet. (2015) Retrospective case series Adult Crohn s disease and Ulcerative colitis 50 Effective for some patients with IBD Obih, C. al Nutrition (2016) * Retrospective case series Pediatric Crohn s and ulcerative colitis Burgis JC, et al World J Gastro (2016) Suskind DL, et al J Clin Gastroenterol. (2016) * Suskind DL, et al Dig Dis Sci. (2016) * Nakayuenyongsuk W, et al Dig Dis Sci. 2017 26 improve clinical and laboratory parameters for pediatric CD as well as UC Retrospective case series Pediatric Crohn s 11 Disease control may be attainable with the SCD in pediatric CD Prospective case series Patient Survey Pediatric Crohn s and ulcerative colitis Pediatric/Adult Crohn s and Ulcerative colitis 13 Clinical improvement, laboratory improvement and microbiome shifts 417 Most patients perceive clinical benefit to use of the SCD Retrospective Case Pediatric Crohn s disease 1 Effective after weaning from EEN Braly, K, et al. JPGN (2017) * Prospective diet evaluation Pediatric Crohn s disease and ulcerative colitis Miller TL, et al, Dig Dis Sci. (2017)* 9 Evaluated dietary intake of patients on the SCD Retrospective case series Pediatric VEO-IBD 2 Clinical, laboratory and mucosal healing for 1 patient
Pediatric Crohn s Disease Activity Index Study ID Prior to Diet Intervention 3 Months After 6 Months After One 20 0 0 Two 30 0 0 12 Months After 15 Months After 18 Months After Three 30 0 0 0 0 Four 10 0 0 0 0 0 Five 15 0 0 0 Nine 25 0 0 Ten 10 0 0 0 Suskind DL, et al, JPGN. 2014 Jan;58(1):87-91.
Suskind DL, et al, JPGN. 2014 Jan;58(1):87-91.
Prospective SCD study Active Crohn s Disease/Ulcerative Colitis Age 8-21 years No change in medication Followed Baseline 2, 4, 8, 12 weeks Clinically, laboratory response, microbiome Suskind, et al, JCG 2016 Dec 27(Epub ahead of print)
PUCAI/PCDAI Prospective SCD study 60 50 40 30 20 10 0 Enrollment 2 weeks 4 weeks 8 weeks 12 weeks Suskind, et al, JCG 2016 Dec 27(Epub ahead of print)
C-reactive protein Prospective SCD study 35 30 25 20 15 10 5 0 Enrollment 2 weeks 4 weeks 8 weeks 12 weeks Suskind, et al, JCG 2016 Dec 27(Epub ahead of print)
Calprotectin Prospective SCD study 1800 1600 1400 1200 1000 800 600 400 200 0 Enrollment 4 weeks 12 weeks Suskind, et al, JCG 2016 Dec 27(Epub ahead of print)
Microbiome Analysis Species Baseline Week 2 Week 6 Week 12 Escherichia coli 12.3 0.3 1.8 0.2 Ruminococcus gnavus 15.0 4.7 4.4 1.9 Bacteroides fragilis 8.2 1.3 12.1 1.1 Bacteroides ovatus 8.4 3.0 1.1 1.6 Veillonella unclassified 4.3 0.1 0.0 0.0 Bacteroides stercoris 6.7 4.6 1.0 2.9 Suskind, et al, JCG 2016 Dec 27(Epub ahead of print)
Suskind, et al, JCG 2016 Dec 27(Epub ahead of print)
PCDAI Crohn s disease: Blind Diet Controlled Study 3 Groups: SCD, SCD+ oats and rice, whole foods minus milk, wheat, corn and processed foods 50 45 40 35 30 25 20 15 10 5 0 Baseline Week 2 Week 4 Week 8 Week 12 ClinicalTrials.gov Identifier: NCT02610101
CRP Crohn s disease: Blind Diet Controlled Study 3 Groups: SCD, SCD+ oats and rice, whole foods minus milk, wheat, corn and processed foods 8 7 6 5 Baseline 4 Week 2 3 Week 4 2 Week 8 Week 12 1 0 ClinicalTrials.gov Identifier: NCT02610101
So what is the best diet Specific Carbohydrate Diet Obih, C. al Nutrition Apri;32(4):418-25 Burgis JC, et al World J Gastro 2016 Cohen et al. JPGN 2014 59(4):516-21 Sigall-Boneh, et al. Inflammatory Bowel Diseases. August 2014 Individually Tailored Exclusion Riordan, Lancet 1993 IgG4 Targeted Exclusion Rajendran, Colorectal Dis 2011 FODMAPs Gearry, J Crohns Colitis 2009 Lacto-ovo-vegetarian fiber rich diet Chiba, World Journal of Gastro. 2010
So what is the best diet It depends
We Know What you eat impacts you fecal microbiome Fecal Microbiome impacts IBD So one should eat well
Studies Abound! Double blind diet control study in Crohn s disease Low animal protein SCD in Ulcerative Colitis Reverse Engineered EEN study in Crohn s disease Tim Zisman MD University of Washington Low Animal Protein SCD study in UC SCD vs Low Residual Diet in Crohn s Disease
Let food be thy medicine - Hippocrates