The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn’s Disease: A Randomized Diet Controlled Trial
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Setting and Participants
2.2. Randomization and Blinding
Study Intervention
2.3. Assessment of Participants
2.4. Metagenomics
2.5. Protein/Metabolite Extraction
2.6. Metaproteomics
2.7. Metabolomics
2.8. Data Analysis
3. Results
3.1. Participant Characteristics
3.2. Clinical Outcomes
3.3. Specific Carbohydrate Diet
3.4. Modified SCD
3.5. Whole Food
3.6. Microbiome
3.6.1. Metagenomics
3.6.2. Metabolomics
3.6.3. Metaproteomics Analysis
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Participant Demographics | ||
---|---|---|
Anthropometrics | Age (y) | 14.4 ± 3.00 |
Age at Diagnosis (y) | 10.9 ± 4.83 | |
Height (cm) | 158 ± 12.9 | |
Weight (kg) | 52.2 ± 13.5 | |
BMI | 20.5 ± 2.96 | |
Sex | Male | 8 (57.1%) |
Female | 6 (42.9%) | |
Disease Phenotype | Inflammatory, non-penetrating, non-stricturing | 14 (100.0%) |
Stricturing only | 0 (0.0%) | |
Penetrating only | 0 (0.0%) | |
Both stricturing and penetrating | 0 (0.0%) | |
Medications | Aminosalicylates | 4 (22.2%) |
Antibiotics for IBD | 0 (0.0%) | |
Biologics | 4 (22.2%) | |
Corticosteroids | 0 (0.0%) | |
Immunomodulators | 3 (16.7%) | |
Other immune suppresants | 0 (0.0%) | |
Rectal Therapy | 0 (0.0%) | |
None | 8 (44.4%) | |
PGA | Normal | 0 (0.0%) |
Mild | 6 (42.9%) | |
Moderate | 8 (57.1%) | |
Severe | 0 (0.0%) |
SaMPLE | Raw Reads | QC Reads | Unclassified a | Human | Richness b | Inv Simpson b |
---|---|---|---|---|---|---|
P001 B | 151,597,524 | 129,774,388 | 28.12% | 1.75% | 4218 | 14.05 |
P001 12 | 154,162,426 | 136,058,126 | 31.97% | 0.30% | 4218 | 12.14 |
P005 B | 147,131,300 | 130,725,972 | 29.74% | 32.42% | 4216 | 4.64 |
P005 12 | 152,188,186 | 132,869,602 | 53.25% | 1.28% | 4216 | 10.86 |
P007 B | 133,198,464 | 114,558,570 | 36.28% | 0.26% | 4215 | 13.57 |
P007 12 | 196,850516 | 172,507,988 | 34.46% | 0.56% | 4217 | 17.68 |
P010 B | 148,457,710 | 123,323,294 | 30.41% | 1.01% | 4216 | 13.87 |
P010 12 | 160,592,310 | 150,922,746 | 25.34% | 0.69% | 4217 | 11.23 |
P015 B | 150,180,158 | 110,457,378 | 32.76% | 1.18% | 4198 | 4.77 |
P015 12 | 165,946,068 | 130,556,042 | 47.70% | 3.04% | 4210 | 15.42 |
Metabolites | 001 | 010 | 015 | 005 | 007 | |||||
---|---|---|---|---|---|---|---|---|---|---|
W02/S | W12/S | W02/S | W12/S | W02/S | W12/S | W02/S | W12/S | W02/S | W12/S | |
1,2-propanediol | 11.5 | 6.7 | 15.4 | 8.6 | 10.5 | 6.2 | 39.7 | 26.7 | 21.0 | 12.8 |
Unknown 002 | 0.0 | 0.0 | 0.0 | 0.0 | 19.9 | 95.3 | 136.7 | 102.1 | 132.8 | 84.0 |
2-piperidinone | 5.7 | 3.8 | 14.4 | 20.2 | 51.9 | 19.4 | 171.6 | 39.3 | 142.7 | 101.3 |
Unknown 018 | 66.4 | 3.8 | 6.0 | 19.8 | 108.7 | 84.2 | 244.0 | 195.1 | 97.8 | 89.6 |
benzenepropanoic acid | 22.2 | 18.5 | 108.6 | 0.0 | 79.8 | 62.0 | 275.2 | 55.9 | 115.2 | 125.1 |
tetrahydro-2-pyranone | 21.6 | 14.3 | 109.7 | 57.4 | 85.6 | 14.0 | 490.7 | 99.8 | 231.6 | 198.3 |
Unknown 010 | 68.8 | 48.6 | 81.8 | 65.1 | 44.2 | 23.2 | 160.7 | 20.4 | 917.5 | 1310.0 |
2-phenylmalonic acid | 40.7 | 33.3 | 93.2 | 67.3 | 65.8 | 44.6 | 383.7 | 72.4 | 112.0 | 146.8 |
Unknown 033 | 144.3 | 90.0 | 0.0 | 0.0 | 102.7 | 23.2 | 304.3 | 126.9 | 112.6 | 51.3 |
p-cresol | 82.0 | 46.6 | 43.5 | 60.2 | 97.8 | 30.7 | 96.6 | 43.8 | 163.5 | 431.9 |
2,6-dimethylpyrazine | 0.0 | 267.8 | 0.0 | 0.0 | 86.3 | 22.3 | 188.8 | 181.8 | 0.0 | 0.0 |
Unknown 012 | 42.0 | 99.2 | 27.5 | 1.7 | 81.8 | 133.3 | 55.6 | 0.0 | 3029.1 | 2395.9 |
Unknown 030 | 68.1 | 82.5 | 50.2 | 36.8 | 135.2 | 37.7 | 151.0 | 263.0 | 91.6 | 139.6 |
butanoic acid | 59.5 | 86.6 | 90.2 | 56.5 | 103.0 | 47.7 | 47.1 | 81.9 | 259.9 | 370.7 |
3-ethyl-2,5-dimethylpyrazine | 111.0 | 111.6 | 2.5 | 120.2 | 82.6 | 20.0 | 238.8 | 122.8 | 1949.6 | 3010.6 |
Unknown 029 | 68.4 | 33.2 | 109.6 | 78.6 | 106.8 | 62.8 | 140.0 | 58.6 | 77.7 | 77.0 |
propanoic acid | 57.9 | 81.8 | 139.0 | 86.9 | 80.2 | 38.2 | 116.4 | 52.6 | 186.6 | 171.7 |
Acetate | 104.3 | 90.0 | 95.5 | 65.0 | 87.5 | 55.5 | 117.8 | 61.9 | 165.5 | 141.7 |
Indole | 69.9 | 32.2 | 128.8 | 90.2 | 99.4 | 86.3 | 134.9 | 74.0 | 70.0 | 73.9 |
furaneol | 97.1 | 85.1 | 143.4 | 53.8 | 78.6 | 54.9 | 262.2 | 149.2 | 181.4 | 119.5 |
3-methylbutanoic acid | 58.2 | 39.5 | 173.8 | 121.3 | 69.2 | 51.3 | 84.3 | 34.4 | 228.3 | 270.3 |
tetradecanoic acid | 101.7 | 104.4 | 156.7 | 38.1 | 116.0 | 2.5 | 168.2 | 60.1 | 140.5 | 141.0 |
isobutyric acid | 55.3 | 48.1 | 183.2 | 117.9 | 73.3 | 48.9 | 48.8 | 23.0 | 212.0 | 228.4 |
4-methylpentanoic acid | 33.3 | 63.8 | 88.9 | 71.8 | 256.7 | 61.4 | 139.0 | 15.2 | 181.3 | 124.7 |
Metabolite | 001_B | 005_B | 007_B | 010_B | 015_B | 001_W2 | 005_W2 | 007_W2 | 010_W2 | 015_W2 | p-Value | Pattern |
---|---|---|---|---|---|---|---|---|---|---|---|---|
oleic acid | 26.24 | 26.56 | 27.35 | 26.88 | 27.19 | 27.38 | 27.99 | 27.65 | 28.50 | 28.13 | 0.0048 | Up |
campesterol | 21.53 | 22.16 | 22.54 | 23.25 | 21.90 | 20.21 | 20.92 | 21.32 | 21.09 | 21.41 | 0.0076 | Down |
stigmasterol | 21.48 | 20.63 | 20.75 | 21.86 | 21.06 | 20.17 | N/A | 20.10 | 19.81 | 20.56 | 0.0113 | Down |
lignoceric acid * | 21.17 | 20.91 | 20.99 | 21.94 | 21.43 | 21.50 | 22.00 | 21.83 | 22.07 | 22.62 | 0.0248 | Up |
1-eicosanol * | 23.06 | 20.75 | 20.28 | 23.03 | 22.01 | 19.97 | 19.97 | 20.49 | 19.16 | 20.81 | 0.0254 | Down |
phosphate ion | 24.61 | 24.37 | 25.55 | 24.11 | 25.10 | 24.74 | 26.81 | 25.87 | 26.26 | 25.67 | 0.0312 | Up |
1-monolinolein * | 21.56 | 22.50 | 22.64 | 21.70 | 22.05 | 22.41 | 22.93 | 22.32 | 22.88 | 23.18 | 0.0404 | Up |
pimelic acid | 19.87 | 21.15 | 19.46 | 19.30 | 22.11 | 21.97 | 21.42 | 21.78 | 21.27 | 21.96 | 0.0490 | Up |
maltose | 19.82 | 20.24 | 20.92 | 19.64 | 20.95 | 20.37 | 19.32 | 18.83 | 18.60 | 19.65 | 0.0494 | Down |
L-cysteine | 20.97 | 21.22 | 20.77 | 21.31 | 22.76 | 21.75 | 24.69 | 23.15 | 22.23 | 22.19 | 0.0585 | Up |
stearic acid | 22.72 | 23.86 | 23.65 | 24.28 | 23.32 | 22.32 | 22.96 | 23.31 | 22.85 | 23.01 | 0.0587 | Down |
3-hydroxypyridine | 17.18 | 18.72 | 19.59 | 17.45 | 16.97 | 19.76 | 20.44 | 21.08 | 19.89 | 17.28 | 0.0706 | Up |
methyl oleate | 21.96 | 22.40 | 23.10 | 22.88 | 21.08 | 20.87 | 24.64 | 24.61 | 25.62 | 25.39 | 0.0715 | Up |
L-glutamic acid | 26.25 | 25.79 | 26.05 | 25.64 | 23.79 | 26.62 | 27.65 | 26.05 | 26.49 | 26.12 | 0.0734 | Up |
N-acetyl-D-mannosamine | 22.94 | 24.14 | 24.32 | 25.04 | 23.36 | 22.55 | 20.95 | 23.72 | 23.19 | 23.34 | 0.0833 | Down |
heptadecanoic acid | 23.77 | 24.25 | 23.90 | 26.11 | 24.01 | 23.27 | 23.42 | 24.06 | 22.90 | 23.75 | 0.0863 | Down |
myristic acid | 24.76 | 24.77 | 24.39 | 25.79 | 24.69 | 24.16 | 23.84 | 25.08 | 23.59 | 24.32 | 0.0865 | Down |
2-oleoylglycerol * | 20.83 | 20.88 | 21.44 | 20.83 | 21.34 | 20.90 | 21.78 | 21.16 | 22.25 | 21.85 | 0.0970 | Up |
palmitic acid | 24.91 | 25.86 | 25.52 | 26.46 | 25.59 | 24.59 | 25.15 | 25.51 | 25.17 | 25.20 | 0.0998 | Down |
Proteins Identified | Human Proteins | % Non-Human Assigned EC | EC Families | EC Diversity (Inv Simpson) | |
---|---|---|---|---|---|
P001 B | 9768 | 550 | 51.00% | 714 | 132 |
P001 2 | 10767 | 444 | 50.10% | 707 | 130 |
P001 12 | 11545 | 371 | 50.62% | 763 | 147 |
P005 B | 5103 | 1353 | 38.53% | 568 | 98 |
P005 2 | 6184 | 1749 | 37.44% | 613 | 95 |
P005 12 | 10483 | 1441 | 43.91% | 761 | 112 |
P007 B | 11034 | 650 | 47.09% | 740 | 103 |
P007 2 | 8289 | 559 | 44.46% | 685 | 97 |
P007 12 | 9086 | 505 | 46.91% | 679 | 107 |
P010 B | 7975 | 585 | 48.54% | 660 | 107 |
P010 2 | 11353 | 697 | 47.08% | 774 | 120 |
P010 12 | 12109 | 718 | 46.73% | 776 | 116 |
P015 B | 3841 | 622 | 40.93% | 551 | 89 |
P015 2 | 4797 | 672 | 40.84% | 609 | 115 |
P015 12 | 6498 | 611 | 44.52% | 655 | 110 |
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Suskind, D.L.; Lee, D.; Kim, Y.-M.; Wahbeh, G.; Singh, N.; Braly, K.; Nuding, M.; Nicora, C.D.; Purvine, S.O.; Lipton, M.S.; et al. The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn’s Disease: A Randomized Diet Controlled Trial. Nutrients 2020, 12, 3749. https://doi.org/10.3390/nu12123749
Suskind DL, Lee D, Kim Y-M, Wahbeh G, Singh N, Braly K, Nuding M, Nicora CD, Purvine SO, Lipton MS, et al. The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn’s Disease: A Randomized Diet Controlled Trial. Nutrients. 2020; 12(12):3749. https://doi.org/10.3390/nu12123749
Chicago/Turabian StyleSuskind, David L., Dale Lee, Young-Mo Kim, Ghassan Wahbeh, Namita Singh, Kimberly Braly, Mason Nuding, Carrie D. Nicora, Samuel O. Purvine, Mary S. Lipton, and et al. 2020. "The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn’s Disease: A Randomized Diet Controlled Trial" Nutrients 12, no. 12: 3749. https://doi.org/10.3390/nu12123749