DOP021 Appendectomy regulates intestinal flora-bile acid axis inhibits macrophage lipid metabolism and improves Ulcerative Colitis

Abstract Background The specific role of the appendix as both an immune organ and a reservoir for gut microbiota in inflammatory bowel disease (IBD) remains elusive. Recent clinical studies have demonstrated that appendectomy can alleviate refractory ulcerative colitis and reduce the rate of colon surgical resection in patients. However, the underlying mechanisms are still unclear. This study aims to comprehensively explore the precise regulatory mechanisms of appendectomy in the process of colonic inflammation. Methods Appendectomy was performed on C57BL/6 mice followed by induction of dextran sulfate sodium (DSS)-induced colitis. Changes in colon length, body weight, and other parameters were evaluated.Quantitative real-time polymerase chain reaction (qPCR), western blot, and immunofluorescence staining were employed to assess production of pro-inflammatory cytokines and the level of colonic mucosal barrier markers. Public databases were utilized for bioinformatics analysis. Transcriptomic, 16S rRNA, and metabolomic sequencing were conducted. Results Appendectomy increased colon length, body weight, and enhanced mucosal barrier integrity in mice with colitis, indicating alleviation of colitis. 16S rRNA sequencing indicated significant differences in microbial taxa such as Mucispirillum, Bacleroides, Clostridium_sensu_stricto_1, Romboutsia genus, Turcicibacter. Metabolomics analysis suggested that secondary bile acids accumulation. Both tanscriptome sequencing and metabolomics analysis enriched in lipid metabolism. Conclusion This study highlights the critical role of' appendectomy in regulating gut microbiota and lipid metabolism, and its contribution to the remission of UC. Appendectomy may hold promise as a therapeutic approach for mitigating colonic inflammation and improving disease outcomes in patients with UC. References 1. Agrawal M, Allin KH, Mehandru S, Faith J, Jess T, Colombel JF. The appendix and ulcerative colitis - an unsolved connection. Nat Rev Gastroenterol Hepatol. 2023;20(9):615-624. doi:10.1038/s41575-023-00774-3 2. Arjomand Fard N, Armstrong H, Perry T, Wine E. Appendix and Ulcerative Colitis: a Key to Explaining the Pathogenesis and Directing Novel Therapies?. Inflamm Bowel Dis. 2023;29(1):151-160. doi:10.1093/ibd/izac106 3. Parian A, Limketkai B, Koh J, et al. Appendectomy does not decrease the risk of future colectomy in UC: results from a large cohort and meta-analysis. Gut. 2017;66(8):1390-1397. doi:10.1136/gutjnl-2016-311550 4. Elmahdi R, Jess T, Andersena NN. Appendectomy in Your First-degree Relative Protects You Against UC. J Crohns Colitis. 2019;13(12):1585. doi:10.1093/ecco-jcc/jjz089