单变量和多变量门德尔随机化研究确定了肠道微生物群在免疫治疗毒性的关键作用
Baike Liu1,2, Zheran Liu3, Tianxiang Jiang1,2
1Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
European journal of medical research
|March 13, 2024
概括
像Lachnospiraceae这样的肠道细菌与接受免疫检查点抑制剂 (ICI) 的癌症患者的免疫相关不良事件 (irAEs) 有因果关系. 一些微生物可以防止irAEs,为管理提供潜在的目标.
科学领域:
- 微生物组研究的研究.
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- 新出现的证据将肠道微生物群与接受免疫检查点抑制剂 (ICI) 的癌症患者的免疫相关不良事件 (irAEs) 联系起来.
- 肠道微生物在irAE发展中的确切因果作用尚不清楚.
研究的目的:
- 在接受ICI治疗的患者中,研究特定肠道细菌种群和irAEs之间的因果关系.
- 识别潜在的微生物生物标记物或治疗点,以管理irAEs.
主要方法:
- 使用单变量和多变量门德尔随机化 (MR) 分析.
- 采用了来自MiBioGen联盟 (18,340名参与者) 的肠道微生物群的仪器变量.
- 通过使用各种MR方法,分析了来自ICI治疗队列 (1751名患者) 的IRE的GWAS总结数据.
主要成果:
- 确定了14种与irAEs因果相关的肠道细菌种群.
- 拉克诺斯皮拉属植物 (Lachnospiraceae) 显示出与高等级和所有等级的irAEs风险增加的强烈关联.
- 阿克尔曼西亚,Verrucomicrobiaceae和Anaerostipes对高等级的irAEs有保护作用,而鲁米尼克洛斯特里6,Coprococcus3,Collinsella和Eubacterium (fissicatena组) 则增加了风险.
结论:
- 建立了拉克诺斯皮拉属和irAEs之间强烈的因果关系,与其他微生物种群一起.
- 研究结果表明,肠道微生物群调节是治疗ICI治疗癌症患者的irAEs的潜在策略.
相关概念视频
Microorganisms in Medicine and Therapeutics
1.4K
Microorganisms play a fundamental role in vaccine development, gene therapy, and therapeutic production. Their biological properties are harnessed to advance medicine and public health. Beyond immunization, microorganisms contribute to gut health, antibiotic synthesis, and genetic disease treatment.Live Attenuated and Inactivated VaccinesLive attenuated vaccines, such as the measles, mumps, and rubella (MMR) vaccine, utilize weakened forms of pathogens to closely resemble natural infections.
1.4K
Introduction to the Human Microbiota
226
Microorganisms colonize various regions of the human body, including the mouth, nasal passages, throat, stomach, intestines, urogenital tract, and skin. The total number of microbial cells is estimated to range from 10¹³ to 10¹⁴—comparable to, or exceeding, the number of human somatic cells. This host–microbiome relationship has led to the conceptualization of humans as supraorganisms, wherein microbial communities perform vital roles in development, immunity,...
226
Development of Human Microbiota
73
The human microbiota begins developing at birth and undergoes continual change as we age. Infancy marks a critical period of microbial sensitivity, offering a “window of opportunity” during which beneficial microbes help mature the immune system. By age three, children typically develop a more stable and diverse microbial community. Newborns acquire microbes from their immediate environment; vaginal delivery favors maternal vaginal microbes, while cesarean births favor microbes from...
73
Microbiota of the Stomach and Small Intestine
95
The human gastrointestinal (GI) tract is characterized by distinct physicochemical conditions that shape its microbial communities. Among these, the stomach presents a particularly challenging environment for microbial colonization due to its highly acidic pH, ranging from 1 to 3. This extreme acidity effectively limits microbial density. However, certain acid-tolerant microorganisms are capable of surviving in this niche. Notably, Helicobacter pylori can colonize the gastric mucosa,...
95
Functions of the Gut Microbiota
257
The gut microbiota includes trillions of microorganisms that colonize the human gastrointestinal tract, including bacteria, archaea, viruses, and fungi. This complex ecosystem plays a critical role in maintaining intestinal and systemic health. Most of these microbes inhabit the large intestine, establishing a relatively stable and diverse community that contributes to gut homeostasis through various metabolic, immunological, and protective mechanisms.Dominant bacterial phyla, such as...
257
Gut-Brain Axis
252
The gut–brain axis is a bidirectional communication system that connects the gastrointestinal tract and the brain. This interaction is mediated through multiple pathways, including the vagus nerve, hormonal signals, immune responses, and chemical messengers produced by gut microbes.Microbial Contributions to Brain FunctionGut microbiota contributes significantly to brain function by producing neuroactive compounds. These include neuroactive compounds that influence neurotransmitters such...
252


