Li Hongjiao, Li Peimin, Guo Xiaofeng, Zhou Yan, Ma Shaowei, Gao Xin
The Stomatology Department of Shanxi Provincial People Hospital, Taiyuan, Shanxi, China.
The Gastroenterology Department of Shanxi Provincial People's Hospital, Taiyuan, Shanxi, China.
Front Immunol. 2025 Aug 27;16:1668277. doi: 10.3389/fimmu.2025.1668277. eCollection 2025.
Ulcerative colitis (UC) and periodontitis (PD) are chronic inflammatory diseases with increasing evidence of bidirectional communication through the oral-gut axis. However, the immunological mechanisms underlying their co-occurrence remain largely unclear.
We conducted a bidirectional Mendelian randomization (MR) analysis to evaluate potential causal relationships between UC and PD. Transcriptomic data from public repositories were integrated to identify shared differentially expressed genes. Immune-related genes were further screened using three machine learning approaches. Enrichment analysis and immune cell infiltration profiling were performed to explore underlying mechanisms. A rat model combining UC and PD was established to validate key findings .
MR analysis revealed a unidirectional causal effect of UC on PD. Among the intersected immune-related genes, CXCL6 was identified as a hub gene significantly upregulated in both UC and PD. It was associated with neutrophil infiltration and pathways related to chemokine signaling and mucosal barrier disruption. In a dual-disease rat model, CXCL6 expression was further elevated in colonic tissues compared to UC alone, aligning with aggravated epithelial damage.
Our study identifies a shared immune signature between UC and PD, highlighting CXCL6 as a pivotal mediator. These insights deepen understanding of oral-gut mucosal interactions and inform future biomarker and mechanistic studies.
溃疡性结肠炎（UC）和牙周炎（PD）是慢性炎症性疾病，越来越多的证据表明它们通过口肠轴进行双向交流。然而，它们同时发生的免疫机制在很大程度上仍不清楚。
我们进行了双向孟德尔随机化（MR）分析，以评估UC和PD之间的潜在因果关系。整合来自公共数据库的转录组数据，以识别共同的差异表达基因。使用三种机器学习方法进一步筛选免疫相关基因。进行富集分析和免疫细胞浸润分析，以探索潜在机制。建立了UC和PD联合的大鼠模型，以验证关键发现。
MR分析揭示了UC对PD的单向因果效应。在相交的免疫相关基因中，CXCL6被确定为在UC和PD中均显著上调的枢纽基因。它与中性粒细胞浸润以及与趋化因子信号传导和粘膜屏障破坏相关的途径有关。在双病大鼠模型中，与单独的UC相比，结肠组织中CXCL6的表达进一步升高，这与上皮损伤加重一致。
我们的研究确定了UC和PD之间共同的免疫特征，突出了CXCL6作为关键介质。这些见解加深了对口肠粘膜相互作用的理解，并为未来的生物标志物和机制研究提供了信息。
