Replacing Animal Protein with Soy-Pea Protein in an American Diet Controls Murine Crohn Disease-Like Ileitis Regardless of Firmicutes: Bacteroidetes Ratio

Background: The current nutritional composition of the American diet (AD; also known as Western diet) has been linked to the increasing incidence of chronic diseases, including inflammatory bowel disease (IBD), namely Crohn disease (CD). Objectives: This study investigated which of the 3 major macronutrients (protein, fat, carbohydrates) in the AD has the greatest impact on preventing chronic inflammation in experimental IBD mouse models. Methods: We compared 5 rodent diets designed to mirror the 2011-2012 What We Eat in America NHANES. Each diet had 1 macronutrient dietary source replaced. The formulated diets were AD, AD-soy-pea (animal protein replaced by soy + pea protein), AD-CHO (refined carbohydrate by polysaccharides), AD-fat [redistribution of the omega-6:omega-3 (n-6:n-3) PUFA ratio; similar to 10:1 to 1:1], and AD-mix (all 3 healthier macronutrients combined). In 3 separate experiments, 8-wk-old germ-free SAMP1/YitFC mice (SAMP) colonized with human gut microbiota (hGF-SAMP) from CD or healthy donors were fed an AD, an AD-modified, or laboratory rodent diet for 24 wk. Two subsequent dextran sodium sulfate-colitis experiments in hGF-SAMP (12-wk-old) and specific-pathogen-free (SPF) C57BL/6 (20-wk-old) mice, and a 6-wk feeding trial in 24-wk-old SPF SAMP were performed. Intestinal inflammation, gut metagenomics, and MS profiles were assessed. Results: The AD-soy-pea diet resulted in lower histology scores [mean SD (56.1% +/- 20.7% reduction)] in all feeding trials and IBD mouse models than did other diets (P < 0.05). Compared with the AD, the AD-soy-pea correlated with increased abundance in Lactobacillaceae and Leuconostraceae (1.5-4.7 log(2) and 3.0-5.1 log(2) difference, respectively), glutamine (6.5 +/- 0.8 compared with 3.9 +/- 0.3 ng/mu g stool, P = 0.0005) and butyric acid (4:0; 3.3 +/- 0.5 compared with 2.54 +/- 0.4 ng/mu g stool, P = 0.006) concentrations, and decreased linoleic acid (18:2n-6; 5.4 +/- 0.4 compared with 8.6 +/- 0.3 ng/mu L plasma, P = 0.01). Conclusions: Replacement of animal protein in an AD by plant-based sources reduced the severity of experimental IBD in all mouse models studied, suggesting that similar, feasible adjustments to the daily human diet could help control/prevent IBD in humans.

Automated summary

The study found that replacing animal protein in the American diet with plant-based sources reduced the severity of experimental IBD in mouse models, suggesting that similar adjustments to the daily human diet could help control/prevent IBD in humans.