Diet-Microbiome Links Diverge in Crohn’s Disease and Ulcerative Colitis

Diet is increasingly recognized as a modifiable component of inflammatory bowel disease (IBD) management, but the path from food intake to intestinal inflammation is unlikely to be uniform across disease phenotypes. A study published in Gut, which collected data longitudinally at baseline and 6 months, suggests that the microbiome may connect diet with inflammation through different routes in Crohn’s disease (CD) and ulcerative colitis (UC), raising the possibility that dietary strategies may ultimately need to account for disease-specific microbial biology.

Investigators at Vall d’Hebron Hospital in Barcelona enrolled 198 adults, including 49 with CD, 49 with UC, and 100 healthy controls. Participants completed a validated food frequency questionnaire and provided stool samples at baseline and 6 months. Dietary quality was assessed using several established indices, while shotgun metagenomic sequencing of 366 samples characterized microbial taxonomy and function. Causal mediation analyses—a statistical method, applied here to cross-sectional associations rather than confirmed temporal sequences—then examined whether microbiome features could help explain associations between habitual diet and inflammatory or clinical outcomes.

IBD Diets Were Narrower, and Microbial Diversity Followed

Compared with healthy controls, patients with CD and UC reported lower overall diet quality and reduced intake across multiple food groups, particularly vegetables, fruits, nuts, and seeds. Both groups consequently consumed less fiber, while patients with CD also reported lower carbohydrate and protein intake.

The microbial differences were similarly graded. CD was associated with the lowest microbial richness and diversity and the greatest dysbiosis, while UC generally occupied an intermediate position between CD and healthy controls. Higher-quality dietary patterns, including greater adherence to Mediterranean-style and healthy plant-based diets, correlated with greater microbial diversity and less dysbiosis.

Individual foods followed a comparable pattern. Fruits, vegetables, legumes, nuts, and seeds were associated with greater diversity, whereas soft drinks, packaged fruit juices, and white bread were associated with lower diversity or greater dysbiosis. Higher fiber intake also tracked with a more diverse, less dysbiotic microbiome. Yet fiber itself showed little relationship with inflammatory markers or disease activity, apart from a modest inverse association with Harvey-Bradshaw Index (HBI) scores in CD (ρ=−0.23; P=0.049).

CD Pointed to Specific Microbial Mediators

The mediation analyses revealed a more nuanced distinction between CD and UC. In CD, broad measures such as microbial richness and dysbiosis did not mediate the observed relationships between diet and inflammation. Instead, specific bacterial taxa emerged as potential intermediaries.

Higher Healthy Eating Index-2015 and Mean Adequacy Ratio scores, as well as coffee consumption, were associated with lower HBI scores through shifts involving Bacteroides caccae, B faecis, and B thetaiotaomicron relative to B fragilis. Whole wheat bread was linked to lower HBI through changes involving Butyricimonas species, Odoribacter splanchnicus, and other taxa. Coffee was also associated with lower fecal calprotectin through greater abundance of Lawsonibacter asaccharolyticus and lower abundance of a Clostridiales bacterium.

Several of these organisms produce short-chain fatty acids (SCFAs), providing a potential functional connection. Mediation analysis estimated that microbial acetate-related metabolism explained nearly one-third of the association between coffee consumption and lower HBI. Conversely, a mixed-acid fermentation pathway mediated more than 80% of the association between soft drink consumption and higher HBI.

UC Showed a Broader Ecological Signal

In UC, the pattern shifted from individual taxa toward overall microbial ecology. Greater adherence to an Alternative Mediterranean Diet was associated with lower C-reactive protein (CRP) and calprotectin through reduced dysbiosis. Fruit and coffee intake were similarly associated with lower inflammatory markers through greater microbial richness and less dysbiosis, while olive oil showed associations mediated by reduced dysbiosis.

An unhealthy plant-based dietary pattern moved in the opposite direction, with higher CRP and calprotectin mediated by reduced microbial richness and increased dysbiosis. Functional analysis also suggested that microbial metabolic pathways may matter: approximately 60% of the association between Mediterranean diet adherence and lower CRP was mediated through an acetylene degradation pathway.

These findings remain hypothesis-generating. Diet was self-reported, the cohort came from a single center, and mediation analysis cannot establish that altering a particular food or organism will reduce inflammation. Importantly, analyses of changes over the 6-month follow-up found no significant relationships between changes in dietary quality and inflammation, possibly reflecting the clinical stability of the cohort. The investigators also treated repeated measurements as independent observations for their primary cross-sectional analyses.

Still, the study moves the diet–microbiome discussion beyond a simple prescription to consume more fiber. It suggests that similar dietary exposures may intersect with inflammation through different microbial architectures in CD and UC. Controlled dietary intervention studies will be needed to determine whether those microbial signatures can serve biomarkers of dietary response or eventually support more individualized nutritional strategies alongside established IBD therapy.

Reference:
Mayorga L, Noguera Segura A, Campderros L, et al. Distinct microbial mediators link diet to inflammation in Crohn’s disease and ulcerative colitis. Gut. 2026;75:1136-1146. doi:10.1136/gutjnl-2025-337480.