TY - JOUR T1 - Deciphering the combinatorial influence of diet and the microbiota on experimental colitis JF - bioRxiv DO - 10.1101/117929 SP - 117929 AU - Sean R. Llewellyn AU - Graham J. Britton AU - Eduardo J. Contijoch AU - Arthur Mortha AU - Jean-Frederic Colombel AU - Ari Grinspan AU - Jose C. Clemente AU - Miriam Merad AU - Jeremiah J. Faith Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/17/117929.abstract N2 - Background & Aims The complex interactions between diet and the microbiota that influence mucosal inflammation and inflammatory bowel disease are poorly understood. Experimental colitis models provide the opportunity to control and systematically perturb diet and the microbiota in parallel to quantify the contributions between multiple dietary ingredients and the microbiota on host physiology and colitis.Methods To examine the interplay of diet and the gut microbiota on host health and colitis, we fed over 40 different diets with varied macronutrient sources and concentrations to specific pathogen free or germ free mice either in the context of healthy, unchallenged animals or colitis models (dextran sodium sulfate (DSS) and T cell transfer).Results Diet influenced physiology in both health and colitis across all models, with the concentration of protein and psyllium fiber having the most profound effects. Increasing dietary protein elevated gut microbial density and worsened DSS colitis severity. Depleting gut microbial density by using germ-free animals or antibiotics negated the effect of a high protein diet. Psyllium fiber influenced host physiology and attenuated colitis severity through microbiota-dependent and microbiota-independent mechanisms. Combinatorial perturbations to dietary protein and psyllium fiber in parallel explain most variation in gut microbial density, intestinal permeability, and DSS colitis severity, and changes in one ingredient can be offset by changes in the other.Conclusions Our results demonstrate the importance of examining complex mixtures of nutrients to understand the role of diet in intestinal inflammation.IBDInflammatory Bowel DiseaseCDCrohn’s DiseaseUCulcerative colitisEENexclusive enteral nutritionDSSdextran sodium sulfateHChigh casein dietLClow casein dietPSYpsyllium dietCELcellulose dietHPSYhigh psyllium dietHCELhigh cellulose dietSCFAshort chain fatty acidsSPFspecific pathogen freeGFgerm freeTregsT regulatory cells ER -