OBJECTIVESInflammatory bowel disease (IBD), sepsis, and intestinal tumors are major health threats. This study aimed to explore the regulatory role of CD177+ neutrophils in the BMP signaling pathway and its impact on the onset, progression, and treatment of these diseases.METHODSGene expression data from the Gene Expression Omnibus (GEO) database for IBD and sepsis were retrieved. Bioinformatics methods like background correction, normalization, and differential expression analysis were used. Weighted gene co-expression network analysis (WGCNA), gene functional enrichment analysis, pan-cancer analysis, single-cell analysis, and in vitro experiments including Caco-2 cell culture, cell proliferation assay (CCK-8), flow cytometry apoptosis analysis, quantitative real-time PCR (qRT-PCR), and plate colony formation assay were performed.RESULTSKey genes associated with IBD and sepsis, such as BMP2, BMP4, BMP6, BMP8A, and CD177, were identified. WGCNA in sepsis found two significant modules related to key clinical outcomes. Core gene screening revealed seven shared genes between IBD and sepsis, and enrichment analysis showed involvement in important biological processes and pathways. Pan-cancer analysis showed diverse gene expression patterns and correlations with immune dynamics. Single-cell transcriptomics provided insights into the tumor microenvironment. In vitro experiments demonstrated that CD177 knockdown affected BMP signaling pathway-related gene expression, ROS production, apoptosis, and cell proliferation.CONCLUSIONCD177+ neutrophils play a crucial role in regulating the BMP signaling pathway in IBD, sepsis, and intestinal tumors. These findings offer potential therapeutic targets, but further clinical validation is required to translate them into effective treatment strategies.