Fecal metabolic signals are associated with changes in microbiota and systemic metabolic pathways in Crohn’s disease

Metabolites play a crucial role in the interactions between the host and its microbiome, influencing disease pathogenesis. To explore metabolic signals linked to Crohn’s Disease (CD), we analyzed paired fecal and serum metabolomics, combined with microbial characterization. Metabolites were identified using liquid chromatography-mass spectrometry, and microbial data were obtained through V4-16 S sequencing and shotgun metagenomics. 202 serum and 294 fecal samples from 80 CD patients and 43 healthy controls were included. Longitudinal analysis highlighted individual variations in metabolic signals and microbial composition. 6602 significant correlations were identified between fecal metabolites and microbes, implying their involvement in microbial-driven disease pathways. Notably, five CD-enriched fecal carbohydrates positively correlated with oral bacteria (e.g., Veillonella parvula, Veillonella dispar, Streptococcus). Additionally, arachidonic acid and three of its derivatives were associated with R. gnavus and Fusobacteria, often implicated in CD pathogenesis. Active CD, defined clinically or by elevated biomarkers (CRP, fecal-calprotectin), exhibited heterogeneous metabolic signatures, with consistent associations between fecal metabolites and established microbial-based indices (CD-related dysbiosis index and alpha diversity). This suggests that specific fecal metabolites potentially sustain microbial imbalances and that targeting metabolic and microbial shifts may offer novel strategies to promote healthier states in CD.