The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn’s Disease: A Randomized Diet Controlled Trial

Background: Crohn’s disease (CD) is a chronic inflammatory intestinal disorder associated with intestinal dysbiosis. Diet modulates the intestinal microbiome and therefore has a therapeutic potential. The aim of this study is to determine the potential efficacy of three versions of the specific carbohydrate diet (SCD) in active Crohn’s Disease. Methods: 18 patients with mild/moderate CD (PCDAI 15–45) aged 7 to 18 years were enrolled. Patients were randomized to either SCD, modified SCD(MSCD) or whole foods (WF) diet. Patients were evaluated at baseline, 2, 4, 8 and 12 weeks. PCDAI, inflammatory labs and multi-omics evaluations were assessed. Results: Mean age was 14.3 ± 2.9 years. At week 12, all participants (n = 10) who completed the study achieved clinical remission. The C-reactive protein decreased from 1.3 ± 0.7 at enrollment to 0.9 ± 0.5 at 12 weeks in the SCD group. In the MSCD group, the CRP decreased from 1.6 ± 1.1 at enrollment to 0.7 ± 0.1 at 12 weeks. In the WF group, the CRP decreased from 3.9 ± 4.3 at enrollment to 1.6 ± 1.3 at 12 weeks. In addition, the microbiome composition shifted in all patients across the study period. While the nature of the changes was largely patient specific, the predicted metabolic mode of the organisms increasing and decreasing in activity was consistent across patients. Conclusions: This study emphasizes the impact of diet in CD. Each diet had a positive effect on symptoms and inflammatory burden; the more exclusionary diets were associated with a better resolution of inflammation.

[1]  S. V. Haas,et al.  The treatment of celiac disease with the specific carbohydrate diet; report on 191 additional cases. , 1955, The American journal of gastroenterology.

[2]  C. McDonald,et al.  Deregulation of intestinal anti-microbial defense by the dietary additive, maltodextrin , 2015, Gut microbes.

[3]  Katherine H. Huang,et al.  Structure, Function and Diversity of the Healthy Human Microbiome , 2012, Nature.

[4]  N. Pace,et al.  Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases , 2007, Proceedings of the National Academy of Sciences.

[5]  T. Zisman,et al.  The microbiota in inflammatory bowel disease: current and therapeutic insights , 2017, Journal of inflammation research.

[6]  Janet K. Jansson,et al.  Twin studies reveal specific imbalances in the mucosa‐associated microbiota of patients with ileal Crohn's disease , 2009, Inflammatory bowel diseases.

[7]  H. Szajewska,et al.  Meta‐analysis: enteral nutrition in active Crohn’s disease in children , 2007, Alimentary pharmacology & therapeutics.

[8]  N. Barnich,et al.  Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation , 2013, Gut.

[9]  A. Boraston,et al.  Structural Biology of Pectin Degradation by Enterobacteriaceae , 2008, Microbiology and Molecular Biology Reviews.

[10]  Rob Knight,et al.  Temporal variability is a personalized feature of the human microbiome , 2014, Genome Biology.

[11]  A. Andoh,et al.  Decreased abundance of Faecalibacterium prausnitzii in the gut microbiota of Crohn's disease , 2013, Journal of gastroenterology and hepatology.

[12]  Laura J. Dixon,et al.  Combinatorial Effects of Diet and Genetics on Inflammatory Bowel Disease Pathogenesis , 2015, Inflammatory bowel diseases.

[13]  A. Day,et al.  Exclusive enteral feeding as primary therapy for Crohn’s disease in Australian children and adolescents: A feasible and effective approach , 2006, Journal of gastroenterology and hepatology.

[14]  J. Bielawski,et al.  Crohn's Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial. , 2019, Gastroenterology.

[15]  S. Vermeire,et al.  Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease , 2012, Inflammatory bowel diseases.

[16]  C. Damman,et al.  The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions , 2016, Therapeutic advances in gastroenterology.

[17]  H. Sokol,et al.  Faecalibacterium prausnitzii and human intestinal health. , 2013, Current opinion in microbiology.

[18]  Torsten Seemann,et al.  Prokka: rapid prokaryotic genome annotation , 2014, Bioinform..

[19]  Kristin E. Burnum-Johnson,et al.  MPLEx: a Robust and Universal Protocol for Single-Sample Integrative Proteomic, Metabolomic, and Lipidomic Analyses , 2016, mSystems.

[20]  Natalie I. Tasman,et al.  A Cross-platform Toolkit for Mass Spectrometry and Proteomics , 2012, Nature Biotechnology.

[21]  Kunihiko Sadakane,et al.  MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph , 2014, Bioinform..

[22]  R. Ley,et al.  Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine , 2006, Cell.

[23]  J. Doré,et al.  Low counts of Faecalibacterium prausnitzii in colitis microbiota , 2009, Inflammatory bowel diseases.

[24]  Ronald J. Moore,et al.  Metabolite, Protein, and Lipid Extraction (MPLEx): A Method that Simultaneously Inactivates Middle East Respiratory Syndrome Coronavirus and Allows Analysis of Multiple Host Cell Components Following Infection , 2019, Methods in molecular biology.

[25]  C. Manichanh,et al.  Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach , 2005, Gut.

[26]  A. Griffiths,et al.  Evaluation of the Pediatric Crohn Disease Activity Index: A Prospective Multicenter Experience , 2005, Journal of pediatric gastroenterology and nutrition.

[27]  Lisa M Bramer,et al.  Dynamics of the human gut microbiome in Inflammatory Bowel Disease , 2017, Nature Microbiology.

[28]  Derrick E. Wood,et al.  Kraken: ultrafast metagenomic sequence classification using exact alignments , 2014, Genome Biology.

[29]  Eric Z. Chen,et al.  Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn's Disease. , 2015, Cell host & microbe.

[30]  Yinjie J. Tang,et al.  Bacterial Metabolism During Biofilm Growth Investigated by 13C Tracing , 2018, Front. Microbiol..

[31]  G. Greenberg,et al.  Controlled trial of bowel rest and nutritional support in the management of Crohn's disease. , 1988, Gut.

[32]  F. Bushman,et al.  Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes , 2011, Science.

[33]  Haas Sv,et al.  The treatment of celiac disease with the specific carbohydrate diet; report on 191 additional cases. , 1955 .

[34]  Omry Koren,et al.  Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome , 2015, Nature.

[35]  Bing Xia,et al.  Increased Proportions of Bifidobacterium and the Lactobacillus Group and Loss of Butyrate-Producing Bacteria in Inflammatory Bowel Disease , 2013, Journal of Clinical Microbiology.

[36]  A. Kurilshikov,et al.  Environment dominates over host genetics in shaping human gut microbiota , 2018, Nature.

[37]  C. McDonald,et al.  Crohn's Disease-Associated Adherent-Invasive Escherichia coli Adhesion Is Enhanced by Exposure to the Ubiquitous Dietary Polysaccharide Maltodextrin , 2012, PloS one.

[38]  Gonçalo R. Abecasis,et al.  The Sequence Alignment/Map format and SAMtools , 2009, Bioinform..

[39]  H. Ogata,et al.  Imbalance in intestinal microflora constitution could be involved in the pathogenesis of inflammatory bowel disease. , 2008, International journal of medical microbiology : IJMM.

[40]  R. Knight,et al.  Bacterial Community Variation in Human Body Habitats Across Space and Time , 2009, Science.

[41]  D. Suskind,et al.  Nutritional Therapy in Pediatric Crohn Disease: The Specific Carbohydrate Diet , 2014, Journal of pediatric gastroenterology and nutrition.

[42]  G. Veres,et al.  ESPGHAN Revised Porto Criteria for the Diagnosis of Inflammatory Bowel Disease in Children and Adolescents , 2013, Journal of pediatric gastroenterology and nutrition.

[43]  Brent S. Pedersen,et al.  Mosdepth: quick coverage calculation for genomes and exomes , 2017, bioRxiv.

[44]  Joshua E. Elias,et al.  Target-Decoy Search Strategy for Mass Spectrometry-Based Proteomics , 2010, Proteome Bioinformatics.

[45]  Samuel I. Miller,et al.  Clinical and Fecal Microbial Changes With Diet Therapy in Active Inflammatory Bowel Disease , 2016, Journal of clinical gastroenterology.

[46]  S. Uccini,et al.  Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn's disease: a randomized controlled open-label trial. , 2006, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[47]  P. Legendre,et al.  vegan : Community Ecology Package. R package version 1.8-5 , 2007 .

[48]  Matthew J. Giefer,et al.  Specific carbohydrate diet for pediatric inflammatory bowel disease in clinical practice within an academic IBD center. , 2016, Nutrition.

[49]  Pavel A. Pevzner,et al.  Universal database search tool for proteomics , 2014, Nature Communications.

[50]  D. Suskind,et al.  A Review of Dietary Therapy for IBD and a Vision for the Future , 2019, Nutrients.

[51]  F. D'armiento,et al.  Short- and long-term therapeutic efficacy of nutritional therapy and corticosteroids in paediatric Crohn's disease. , 2006, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[52]  Srinivas Aluru,et al.  Efficient Architecture-Aware Acceleration of BWA-MEM for Multicore Systems , 2019, 2019 IEEE International Parallel and Distributed Processing Symposium (IPDPS).

[53]  Anders F. Andersson,et al.  A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. , 2010, Gastroenterology.

[54]  Miriam L. Land,et al.  Trace: Tennessee Research and Creative Exchange Prodigal: Prokaryotic Gene Recognition and Translation Initiation Site Identification Recommended Citation Prodigal: Prokaryotic Gene Recognition and Translation Initiation Site Identification , 2022 .

[55]  Jason M. Wood,et al.  Diel metabolomics analysis of a hot spring chlorophototrophic microbial mat leads to new hypotheses of community member metabolisms , 2015, Front. Microbiol..

[56]  K. Svenson,et al.  Diet dominates host genotype in shaping the murine gut microbiota. , 2015, Cell host & microbe.