Issues at Hand. Inflammatory Bowel Disease Paradigm. Diet changes the fecal microbiome. Experience with diet in IBD

Transcription

1 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

2 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?

3 Intestinal Health Lining of the Gut Community of Bacteria Microbiome MUCOSAL INTEGRITY Immune System Body s Defense System Vindigni, S Ther Adv Gastroenter (4):606-25

4 Importance of focusing on the environment/microbiome Bach, New England J Med 2002;347:911-20

5 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

6 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: Backhed, F,et al Science. 2005; 307:

7 Valm et al, PNAS 2011

8 Keeping things in Check Protective Coating Physiochemical barrier composed of a thick mucus layer Secondary defense tight junctions Bactericidal proteins Immune Cells

9 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 (4):606-25

10 Animal Model of Diet and Microbiome E. coli R. gnavus F. prausnitzii B. fragilis C. difficile B.stercoris S. cerevisiae

11 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

12 Diet Rapidly and reproducibly alters human gut microbiome David, L, et al Nature 2014; 505 (7484):

13 Western diet increases Bad Bacteria with increased E. coli in CEABAC10 mice Martinez-Medina M, et al Gut 2014;63:

14 Food Additives: Additional Culprits Maltodextrin: Intestinal defense Processed starch 60% of all packaged items Nickerson, K. et al Gut Microbes 6:1, Nickerson, K, et al PLoS One 2012/2014

15 More Dietary Emulsifiers: CMC and Polysorbate 80 Chassaing B, et al. Nature 519,92-96(2015)

16 Dietary emulsifiers promote colitis in susceptible mice Chassaing B, et al. Nature 519,92-96(2015)

17 Clinical Evidence?!?

18 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): , 2007

19 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): Suskind DL, et al, JPGN Jan;58(1):87-91.

20 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 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

21 Pediatric Crohn s Disease Activity Index Study ID Prior to Diet Intervention 3 Months After 6 Months After One Two Months After 15 Months After 18 Months After Three Four Five Nine Ten Suskind DL, et al, JPGN Jan;58(1):87-91.

22 Suskind DL, et al, JPGN Jan;58(1):87-91.

23 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)

24 PUCAI/PCDAI Prospective SCD study Enrollment 2 weeks 4 weeks 8 weeks 12 weeks Suskind, et al, JCG 2016 Dec 27(Epub ahead of print)

25 C-reactive protein Prospective SCD study Enrollment 2 weeks 4 weeks 8 weeks 12 weeks Suskind, et al, JCG 2016 Dec 27(Epub ahead of print)

26 Calprotectin Prospective SCD study Enrollment 4 weeks 12 weeks Suskind, et al, JCG 2016 Dec 27(Epub ahead of print)

27 Microbiome Analysis Species Baseline Week 2 Week 6 Week 12 Escherichia coli Ruminococcus gnavus Bacteroides fragilis Bacteroides ovatus Veillonella unclassified Bacteroides stercoris Suskind, et al, JCG 2016 Dec 27(Epub ahead of print)

28 Suskind, et al, JCG 2016 Dec 27(Epub ahead of print)

29 PCDAI Crohn s disease: Blind Diet Controlled Study 3 Groups: SCD, SCD+ oats and rice, whole foods minus milk, wheat, corn and processed foods Baseline Week 2 Week 4 Week 8 Week 12 ClinicalTrials.gov Identifier: NCT

30 CRP Crohn s disease: Blind Diet Controlled Study 3 Groups: SCD, SCD+ oats and rice, whole foods minus milk, wheat, corn and processed foods Baseline 4 Week 2 3 Week 4 2 Week 8 Week ClinicalTrials.gov Identifier: NCT

31 So what is the best diet Specific Carbohydrate Diet Obih, C. al Nutrition Apri;32(4): Burgis JC, et al World J Gastro 2016 Cohen et al. JPGN (4): 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

32 So what is the best diet It depends

33 We Know What you eat impacts you fecal microbiome Fecal Microbiome impacts IBD So one should eat well

34 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

35 Let food be thy medicine - Hippocrates