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 ω-6:ω-3 (n-6:n-3) PUFA ratio; ∼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 log2 and 3.0-5.1 log2 difference, respectively), glutamine (6.5 ± 0.8 compared with 3.9 ± 0.3 ng/μg stool, P = 0.0005) and butyric acid (4:0; 3.3 ± 0.5 compared with 2.54 ± 0.4 ng/μg stool, P = 0.006) concentrations, and decreased linoleic acid (18:2n-6; 5.4 ± 0.4 compared with 8.6 ± 0.3 ng/μL 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.