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Lactylation-Related Genes in Ulcerative Colitis: A Multiomics Mendelian Randomization Study for Therapeutic Target

Na An¹, Ruiyun Wang², Huiping Jiao³

¹Anorectal Department, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China, sdutcm.edu.cn.

|June 29, 2026

Summary

Lactylation modification, particularly STMN1 and EP300 genes, plays a causal role in ulcerative colitis (UC) pathogenesis. Increased STMN1 expression in UC suggests its involvement in immune imbalance and potential as a diagnostic marker.

Keywords:

Mendelian randomization lactylation multiomics integration qPCR spatial transcriptome ulcerative colitis

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Area of Science:

Gastroenterology
Immunology
Genetics

Background:

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with increasing global incidence.
Its precise pathogenesis is not fully understood, but lactylation modifications are linked to inflammation.
Investigating lactylation offers insights into UC development and potential treatments.

Purpose of the Study:

To explore the role of lactylation in the pathogenesis of ulcerative colitis (UC).
To identify specific genes involved in lactylation that causally influence UC.
To provide a genetic basis for novel diagnostic markers and therapeutic strategies for UC.

Main Methods:

Utilized Mendelian randomization (MR) analysis with large-scale genetic and clinical data (Finnish database, 482,657 participants).
Integrated eQTL data, SMR analysis, and differential gene expression analysis (GEO dataset).
Validated findings using cell inflammation models (LPS-induced colonic epithelial cells) and molecular techniques (qPCR, spatial transcriptomics).

Main Results:

Identified EP300, LDHC, and STMN1 as causal genes in UC pathogenesis via lactylation.
Confirmed significant upregulation of EP300 and STMN1 in UC patient data.
STMN1 showed enrichment in B cells and monocytes, with the most significant upregulation observed in qPCR and spatial transcriptome analyses.

Conclusions:

STMN1 and EP300 are identified as key causal genes in ulcerative colitis.
Elevated STMN1 expression in UC, particularly in immune cells, suggests a role in immune dysregulation.
Lactylation may contribute to UC pathogenesis by driving immune imbalance, paving the way for new diagnostic and therapeutic approaches.