Pathogenic Mechanism of the Lactylation-Related Gene DCBLD1 in Ulcerative Colitis: A Multi-Omics and Machine Learning Analysis.

Abstract

Background: The incidence of ulcerative colitis (UC) has been steadily increasing in recent years. Current treatments are only effective for some patients, highlighting the need to find novel therapeutic targets. Lactylation, a post-translational modification, remains poorly understood in UC. This study examines the role of the lactylation-related gene DCBLD1 in the pathogenesis of UC through multi-omics analysis.

Methods: Summary-data-based Mendelian Randomization (SMR) analysis identified DCBLD1 as a lactylation-related gene associated with UC risk. Single-cell RNA sequencing (scRNA-seq) examined DCBLD1 expression in UC and healthy intestinal tissues, coupled with cellular communication, metabolic pathway, KEGG enrichment, and GO annotations. Diagnostic models were built based on differential expression between DCBLD1+ and DCBLD1- epithelial cells. In addition, RNA sequencing (RNA-seq) was used for analysis. Ultimately, qPCR was performed to validate DCBLD1 expression.

Results: SMR demonstrated that DCBLD1 positively correlated with UC risk. scRNA-seq revealed that DCBLD1+ epithelial cells exhibited enhanced cellular communication and metabolic activity. Seventeen hub genes were screened for machine learning, yielding AUC values of 0.69 (CATboost), 0.63 (XGBoost), and 0.55 (NGboost) in the test set. RNA-seq confirmed the association of DCBLD1 with immune responses. qPCR confirmed elevated DCBLD1 expression in UC tissues versus controls.

Discussion: Intestinal epithelial cells expressing DCBLD1 may promote inflammation in UC by lactylation, regulating immunometabolism, and participating in immunological responses, all of which require further investigation in the future.

Conclusion: DCBLD1 may promote UC progression through lactylation, immune-metabolic regulation, and involvement in immune responses, serving as a potential therapeutic target.