Habitual Ultra-processed Food Intake Is Associated with Gut Dysbiosis and Pro-inflammatory Metabolite Profiles in...

Ultra-processed food (UPF) is increasingly consumed worldwide and may influence gut microbial ecology relevant to inflammatory bowel disease (IBD). However, patient-level multi-omics data remains scarce. We investigated whether habitual UPF intake is associated with specific microbiota and metabolite profiles in Korean patients with IBD.

Dietary intake was assessed using a validated food frequency questionnaire, and food was categorized by the NOVA system. UPF intake was expressed as percent of energy, and 313 patients were stratified into UPF low (Q1-Q2) and UPF high (Q3-Q4). Fecal samples of 174 patients underwent 16S rRNA sequencing and untargeted metabolomics. Microbiome differences were tested using PERMANOVA for beta-diversity and Mann-Whitney U tests for taxa. Differential metabolites were defined by p < 0.05 and |fold change|≥ 1.5, followed by Reactome enrichment with FDR correction. Correlations among microbiota, metabolites, and UPF subgroups were examined using Spearman tests with Benjamini-Hochberg adjustment. Associations between UPF intake and clinical characteristics were analyzed using Spearman tests, η² from ANOVA and point-biserial correlation.

Microbial beta-diversity differed significantly between UPF low and UPF high participants. UPF high participants showed expansion of pro-inflammatory pathobionts (Escherichia-Shigella, Proteus, Parasutterella, Enterococcus, Fusobacterium, and Clostridium innocuum group) and depletion of anti-inflammatory commensals (Faecalibacterium, Butyricicoccus, Lachnospiraceae ND3007 group, and Bifidobacterium). Metabolomic profiling revealed enrichment of inflammatory pathways (phospholipid metabolism, eNOS/NO signaling, mitochondrial β-oxidation, FMO3-mediated TMA to TMAO, tryptophan catabolism) and reduction of anti-inflammatory metabolites (AHR ligands, BAAT-conjugated bile acids). Integrated analyses demonstrated significant correlations between dysbiotic taxa and inflammatory metabolites. Among NOVA-defined UPF subgroups, sugar-sweetened beverages, ready-to-eat dishes, and packaged snacks and confectioneries showed the strongest associations with these adverse signatures. Analysis of clinical characteristics showed trends between total UPF intake and inflammatory markers (WBC, CRP, fecal calprotectin), and association with upper gastrointestinal tract involvement in patients with CD. Subgroup analysis showed that sugar-sweetened beverage intake was significantly associated with CRP elevation and upper gastrointestinal involvement in patients with CD.

In IBD, higher UPF intake, particularly from specific NOVA-defined subgroups, is associated with gut dysbiosis and a pro-inflammatory metabolome, which in turn correlates with unfavorable clinical characteristics. These findings provide patient-based multi-omics evidence and underscore clinically relevant dietary targets for IBD management.