肠道微生物组和与炎症相关的蛋白质对口腔白血病的影响:孟德尔的随机化研究和调解分析
Junlong Da1, Yinting Ren2, Shiwei Liu1
1Department of Stomatology Center, The First People's Hospital of Foshan, Foshan, China.
Frontiers in oncology
|October 10, 2024
概括
这项研究揭示了与口腔白血病 (OL) 风险相关的肠道细菌. 介素-18受体1 (IL18-R1) 调解肠道细菌和OL之间的通路,提供新的治疗点.
科学领域:
- 研究肠道微生物群,炎症和口腔潜在恶性疾病之间的复杂相互作用.
- 采用先进的遗传流行病学技术,探索复杂疾病的因果关系.
背景情况:
- 口腔白血病 (OL) 是最常见的潜在恶性口腔疾病.
- 新出现的证据表明,肠道微生物群 (GM) 与口腔癌的发展之间存在联系.
- 转基因在OL中的确切因果作用和细胞因子的调解功能在很大程度上仍未确定.
研究的目的:
- 阐明肠道微生物群组成和口腔白血病的发展之间的因果关系.
- 研究肠道微生物群-OL轴中的与炎症相关的蛋白质的潜在调解作用.
- 通过了解其病因路径来确定OL的新型治疗点.
主要方法:
- 使用双样本的门德尔随机化 (MR) 设计,利用全基因组关联研究 (GWAS) 肠道微生物组 (MiBioGen联盟,n=18340) 和口腔白血病 (芬兰人群,513例,411668对照) 的数据.
- 应用了各种MR方法 (IVW,MR Egger,加权中位数,简单模式,加权模式) 来进行可靠的因果推断.
- 进行了灵敏度分析,反向MR分析和调解分析,以验证发现并探索机制性途径.
主要成果:
- 确定了五种与OL发展潜在因果关系的细菌种群; *Clostridiaceae家族1*显示出负相关性,而 *Dorea属*, *Ruminococcus属1*, *Senegalimasilia属*和 *Veillonella属*显示出正相关性.
- 确立了特定的与炎症相关的蛋白质,即介素-10受体亚单元α (IL-10RA) 和介素-18受体1 (IL18-R1) 和OL发生之间的潜在因果关系.
- 调解分析显示,IL18-R1在连接肠道微生物群中的Senegalimasilia属*与口腔白血病的途径中充当调解者.
结论:
- 这项研究强调了肠道微生物群,炎症和口腔白血病之间的重要,复杂的关系.
- 这些发现为针对肠道微生物群的潜在治疗策略提供了新的见解,用于OL预防,诊断和治疗.
- 鉴定IL18-R1的调解作用为未来的干预提供了一个特定的分子点.
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