P1324 Integrated multiomic profiling reveals distinct signatures in Short Bowel Syndrome and Crohn’s Disease patients at variable risk for Intestinal Failure

Background Short bowel syndrome (SBS) and intestinal failure (IF) represent severe outcomes of Crohn’s disease (CD). The mechanisms driving SBS and the transition from low to high SBS risk remain unclear. This study aimed to define metabolic and microbiome signatures across SBS, CD low-risk (CD_LR) and CD high-risk (CD_HR) patients using integrative multi-omics. Methods 73 patients with CD (18 SBS, 40 CD_LR, 15 CD_HR) were consecutively enrolled in a multicenter study and serum and fecal samples were collected and analyzed. Microbiota composition was assessed by 16S rRNA sequencing, evaluating α-/β-diversity, phylum/genus distribution and functional pathway differences. Metabolomics and lipidomics were performed using LC- and FIA-based platforms. Results Metagenomic profiling showed highest α-diversity in CD_LR, intermediate in CD_HR and lowest in SBS. β-diversity revealed clear clustering. SBS exhibited reduced Bacteroidota, increased Proteobacteria and depletion of Faecalibacterium. CD_HR was marked by reduced Akkermansia and increased Ruminococcus compared with CD_LR. Serum metabolomics showed that SBS exhibited marked amino-acid accumulation and broad depletion of complex lipids, consistent with malabsorption and increased protein turnover. CD groups displayed higher carboxylic acids, TCA intermediates and fatty acids, with CD_HR showing the strongest enrichment, indicating intensified energy metabolism. ANOVA identified significant differences across 21 LC and 56 FIA metabolites, with SBS showing the greatest divergence and CD_HR enriched in phosphoglycerides, phosphatidylinositols, phosphatidylethanolamines and ceramides compared with CD_LR. Fecal metabolomics confirmed clear separation: SBS displayed elevated choline and glycine, indicating impaired phospholipid digestion. CD_LR showed higher xanthine, hypoxanthine, spermidine, β-alanine, 5-AVA and TCA intermediates, reflecting active purine and polyamine metabolism. CD_HR differed from CD_LR in BABA, choline and p-cresol-sulfate. Conclusion SBS, CD_LR and CD_HR present distinct metabolic and microbial signatures. SBS shows severe dysbiosis and metabolic depletion, whereas CD_HR is characterized by heightened energy metabolism and lipid remodeling. These findings highlight biomarkers and potential mechanistic pathways relevant to IF risk stratification. Further analyses are underway to validate these findings. Reference: Founding: PNRR-MAD-2022-12376791_Finanziato dall’Unione Europea – NextGenerationEU Titolo: Changing the future of intestinal failure in intestinal chronic inflammation: towards innovative predictive factors and therapeutic targets. Conflict of interest: Prof. Dr. Lopetuso, Loris Riccardo: No conflict of interest Petito, Valentina: None De Maio, Flavio: No conflict of interest Santucci, Lavinia: No conflict of interest Cicchinelli, Michela: No conflict of interest Masi, Letizia: None Troisi, Sara: No conflict of interest Becherucci, Guia: No conflict of interest Migliore, Greta: No conflict of interest Pane, Cesare: No conflict of interest Di Mattia, Miriam: No conflict of interest Profeta, Francesca: No conflict of interest Foscarini, Elisa: No conflict of interest Ennas, Sara: No conflict of interest Pizzoferrato, Marco: No conflict of interest Gervasoni, Jacopo: No conflict of interest Masucci, Luca: No conflict of interest Cammarota, Giovanni: No conflict of interest Gasbarrini, Antonio: No conflict of interest Scaldaferri, Franco: No conflict of interest Papa, Alfredo: No conflict of interest