Distinct microbial mediators link diet to inflammation in Crohn’s disease and ulcerative colitis

BACKGROUND: Inflammatory bowel disease (IBD) arises from complex interactions among diet, host and gut microbiome. Although diet influences intestinal inflammation, the microbial and metabolic pathways involved, and their differences between Crohn's disease (CD) and ulcerative colitis (UC), the two main subtypes of IBD remain unclear. OBJECTIVE: To investigate how the gut microbiome mediates the effects of habitual diet on inflammatory activity in IBD. DESIGN: This longitudinal study included 198 adults (100 healthy controls, 49 CD, 49 UC), participants completed a validated food frequency questionnaire. Dietary quality was evaluated using established indices (Alternative Mediterranean Diet, Healthy Eating Index-2015, Índice de Alimentación Saludable, Mean Adequacy Ratio, Plant-Based Dietary Indexes, Healthy Food Diversity). Participants also provided two stool samples (baseline and 6 months). Shotgun metagenomics (n=366) enabled taxonomic and functional profiling. Causal mediation analyses were used to identify microbial features mediating the effect of diet on inflammation. RESULTS: IBD patients exhibited lower dietary diversity, fibre intake and nutritional adequacy compared with controls. Microbiome diversity was lowest in CD, intermediate in UC and correlated positively with higher intake of fibre, fruit, vegetables and nuts, and negative with processed foods and sugary beverages. Causal mediation analyses revealed that in CD, coffee, whole wheat bread and healthier diets lowered the Harvey-Bradshaw index through specific bacterial species and metabolites. In UC, Mediterranean-like diets, fruits and coffee reduced C reactive protein via greater microbial richness, reduced dysbiosis and short-chain fatty acid-related functions. CONCLUSION: Diet quality influences inflammation in IBD through distinct microbiome pathways: specific taxa and metabolites mediate effects in CD, whereas microbial richness and global composition drive protection in UC.