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

Abstract

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.

Keywords: Crohn’s disease; inflammatory bowel disease; microbiome; multi-omics application; nutrition; specific carbohydrate diet.

Figure 1

Experimental Design of Blinded Diet Controlled Study in Active Crohn’s Disease. Patients followed from Baseline visit (B) to Week 12 (W12) at specified time points with clinical assessment (PCDAI; Pediatric Crohn’s Disease Activity Index), laboratory assessment (C-reactive protein, sedimentation rate, complete blood count, and calprotectin) as well as metagenomics, metabolomics, and proteomic assessment (in highlighted patients: P001, P005, P007, P010, and P015). Specified diets are denoted as SCD (Specific Carbohydrate diet; blue), MSCD (Modified Specific Carbohydrate diet; yellow) and WF (Whole foods; green).

Figure 2

Consort Flow Diagram.

Figure 3

Clinical and laboratory outcomes during dietary therapy. (A) Pediatric Crohn’s disease Activity index per dietary therapy (SCD, MSCD, and WF) over 12 week study period (B) C-reactive protein per patient per dietary therapy (orange = SCD; blue = MSCD; red = WF) over 12 week study period.

Figure 4

Microbiome community structure NMDS. Taxonomy of individual reads, as assigned by Kraken2, was compared between timepoints (baseline and week 12 only). Non-metric multi-dimensional scaling was used to plot the data. The individuality of each patient’s microbiome is evident from patient-specific distances being closer than treatment-specific or timepoint-specific distances. The week 12 spread is less than the baseline spread, indicating more similar community composition following dietary treatment.

Figure 5

Functions and metabolites changing in abundance under the SCD diet. Proteomics results, grouped by EC classification, from week 2 samples were compared against baseline samples. Functions showing a more than 2-fold increase or decrease in at least one patient are highlighted. EMBL’s Interactive Pathways Explorer v3 (iPath3) was used for visualization (doi:10.1093/nar/gyk299). Metabolites that changed in abundance are also highlighted (circles). Navy blue, decreased abundance (p ≤ 0.05); tan, increased abundance (p ≤ 0.1); yellow, increased abundance (p ≤ 0.05). Interactive figures are available at https://pathways.embl.de/selection/wHoxRtfd7dXNlBRp2tz.

Figure 6

Functions and metabolites changing in abundance under the MSCD diet. For patients transitioned to the MSCD diet proteomics results, grouped by EC classification, from week 12 samples were compared against week 2 samples. Metabolites that increased over this time period are also highlighted (circles). Data is presented, as described in Figure 5. Interactive figures are available at https://pathways.embl.de/selection/9W7hzGUbabnlDYQQitH.

Figure 7

Functions and metabolites changing in abundance under the WF diet. For patients transitioned to the WF diet proteomics results, grouped by EC classification, from week 12 samples were compared against week 2 samples. Metabolites that increased over this time period are also highlighted (circles). Data is presented, as described in Figure 5. Interactive figures are available at https://pathways.embl.de/selection/lmukWBizoWD7FIQHot.