A Randomized Controlled Trial Comparing Soy-Pea Protein to Animal Protein in Adults with Crohn's Disease

Diet plays a critical role in managing Crohn's disease (CD) inflammation. We assessed whether dietary replacement of animal protein (AnimalP) by soy-pea protein (SoyP) decreases the pro-inflammatory potential of gut microbiota and intestinal inflammation in CD patients.

In an open-label, randomized controlled feeding trial at University Hospitals Cleveland Medical Center, CD participants and healthy controls were randomized (1:1) to a soy-pea or animal protein diet for 7-days. Primary outcomes were the absolute difference (Δd7-d0) in; Crohn's Disease Activity Index (CDAI) score and fecal myeloperoxidase (MPO). Secondary outcomes included fecal calprotectin (FC) and high-sensitivity C-reactive protein (hsCRP). Murine fecal transplantation experiments were performed to determine the inflammatory potential of diet-altered gut microbiota.

The study randomized 66 participants, of whom 60 were included in the final analysis (n=31 CD, n=29 HC). After 7 days, CD participants assigned to the SoyP diet were more likely than those assigned to the AnimalP diet to demonstrate reductions in fecal MPO (RR=2.30, 95% CI: 1.04-4.85, P=0.032) and HBI (RR=4.68, 95% CI: 1.22-17.98, P=0.009). The association between SoyP and reduced fecal MPO remained significant after Bonferroni adjustment (FWER-adjusted P=0.006). A similar directional trend was observed for CDAI (RR=1.52, 95% CI: 0.89-2.58, P=0.135), although this did not reach statistical significance. No participants experienced worsening of CDAI. The exploratory post hoc rank-based CDAI-MPO composite score was lower in the CD-SoyP versus CD-AnimalP group (median [IQR]: 5 [4-6] vs 8 [7-9]; P=0.012). Stratified analyses demonstrated significant reductions in fecal MPO among CD participants with lower baseline disease activity (CDAI <150; P<0.0001), but not among those with higher disease activity (P=0.799).

Short-term addition of plant-based soy-pea protein within a controlled diet was associated with reductions in objective inflammatory markers in CD, with evidence of greater effects among participants with lower baseline disease activity. ClinicalTrials.gov, Number NCT04065048.