P0182Altered SCFA Metabolism Following Intestinal Resection: A Mechanistic Link Between Dysbiosis and Adverse Outcome in SBS?

Abstract Background Short bowel syndrome (SBS) often develops after ileocaecal resection (ICR), particularly in Crohn’s disease (CD), and is associated with impaired intestinal absorption and accompanied by microbial dysbiosis. Short-chain fatty acids (SCFAs) are key microbial products and crucial for epithelial integrity and mucosal immune homeostasis 1,2. The aim of this study was to investigate the impact of ICR on SCFA profiles and inflammatory changes of the colon. Methods SAMP1/YitFc mice (SAMP1, n = 51) with spontaneous Crohn’s-like ileitis and AKR controls (n = 48) underwent 40% ICR and jejuno-colonic anastomosis or sham surgery (anastomosis without resection). SCFAs were quantified in caecum and stool using liquid chromatography-tandem mass spectrometry. Inflammatory activity and adaptation were assessed via histopathology, lipocalin-2 measurements, and cytokine expression in mesenteric lymph nodes. Ongoing analyses include multicolor spectral flow cytometry (FC) of immune populations in small intestine, colon, spleen, MLN, and functional mucus analyses. Results Pre-operatively, SAMP1 mice displayed significantly elevated caecal SCFA levels of acetate, butyrate and propionate compared with controls (p ≤ 0.05–0.0001). ICR caused a reduction of multiple SCFAs in both strains by day 14, independent of underlying ileitis. This decline coincided with increased stool lipocalin-2, suggesting a disturbance of colonic homeostasis. Following ICR, locally elevated IL4 and IFNγ mRNA levels normalised (d0 vs. d14 p ≤ 0.05) and the inflammation score in the small intestine decreased (d0 vs. d14, p ≤ 0.01) in mice with ileitis. FC-based immunophenotyping will determine how SCFA-loss influences local and systemic immune compartments. Conclusion Colonic adaptation following ICR was investigated for the first time in a CD model. ICR induces a substantial reduction in SCFAs and disrupts host–microbiome homeostasis regardless of chronic ileitis. Given the central role of SCFAs in barrier function and immune regulation, their post-operative depletion may contribute to dysbiosis and inflammation observed in SBS and CD patients. Ongoing immune profiling will help identify SCFA-dependent pathways relevant for improving post-operative outcomes. References: 1 Berlin et al. “Dysbiosis and reduced small intestinal function are required to induce intestinal insufficiency in mice.” American journal of physiology. Gastrointestinal and liver physiology vol. 324,1 (2023): G10-G23. doi:10.1152/ajpgi.00201.2022 2 Wong et al. “Colonic Health: Fermentation and Short Chain Fatty Acids.” Journal of Clinical Gastroenterology 40(3):p 235-243, March 2006. Conflict of interest: Ms. Jadzewski, Elena: No conflict of interest Oswald, Stefan: No conflict of interest Krafft, Jerome: No conflict of interest Reiner, Johannes: No conflict of interest Lamprecht, Georg: No conflict of interest Witte, Maria: No conflict of interest Berlin, Peggy: No conflict of interest