What question did this study set out to answer?

This study aims to characterize the metabolic and microbiome signatures in patients with short bowel syndrome and Crohn’s disease at varying risks of intestinal failure.

January 23, 2026

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

Puntos clave

This study aims to characterize the metabolic and microbiome signatures in patients with short bowel syndrome and Crohn’s disease at varying risks of intestinal failure.
Enrolled 73 patients (18 SBS, 40 CD_LR, 15 CD_HR) in a multicenter study.
Conducted 16S rRNA sequencing to assess microbiota composition and diversity.
Performed metabolomics and lipidomics using LC- and FIA-based platforms.
Analyzed differences in microbial and metabolic profiles across patient groups.
SBS showed the lowest α-diversity, while CD_LR exhibited the highest.
SBS had significant dysbiosis with increased Proteobacteria and decreased Bacteroidota.
Metabolomics revealed marked amino-acid accumulation in SBS and energy metabolism intensification in CD_HR.
Clear separation of metabolic profiles was confirmed in fecal samples across groups.

Resumen

Abstract 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 (CDLR) and CD high-risk (CDHR) patients using integrative multi-omics. Methods 73 patients with CD (18 SBS, 40 CDLR, 15 CDHR) 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 CDLR, intermediate in CDHR and lowest in SBS. β-diversity revealed clear clustering. SBS exhibited reduced Bacteroidota, increased Proteobacteria and depletion of Faecalibacterium. CDHR was marked by reduced Akkermansia and increased Ruminococcus compared with CDLR. 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 CDHR 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 CDHR enriched in phosphoglycerides, phosphatidylinositols, phosphatidylethanolamines and ceramides compared with CDLR. Fecal metabolomics confirmed clear separation: SBS displayed elevated choline and glycine, indicating impaired phospholipid digestion. CDLR showed higher xanthine, hypoxanthine, spermidine, β-alanine, 5-AVA and TCA intermediates, reflecting active purine and polyamine metabolism. CDHR differed from CDLR in BABA, choline and p-cresol-sulfate. Conclusion SBS, CDLR and CDHR present distinct metabolic and microbial signatures. SBS shows severe dysbiosis and metabolic depletion, whereas CDHR 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-2022-12376791Finanziato 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

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