Abstract：
The gut microbiota influences the clinical responses of cancer patients to immunecheckpoint inhibitors (ICIs). However, there is no consensus definition of detrimental dysbiosis. Based on metagenomics (MG) sequencing of 245 non-small cell lung cancer (NSCLC) patient feces, we constructed species-level co-abundance networks that were clustered into species-interacting groups (SIGs) correlating with overall survival. Thirty-seven and forty-five MG species (MGSs) were associated with resistance (SIG1) and response (SIG2) to ICIs, respectively. When combined with the quantification of Akkermansia species, this procedure allowed a person-based calculation of a topological score (TOPOSCORE) that was validated in an additional 254 NSCLC patients and in 216 genitourinary cancer patients. Finally, this TOPOSCORE was translated into a 21-bacterial probe set-based qPCR scoring that was validated in a prospective cohort of NSCLC patients as well as in colorectal and melanoma patients. This approach could represent a dynamic diagnosis tool for intestinal dysbiosis to guide personalized microbiota-centered interventions.
摘要：
肠道菌群影响癌症患者对免疫检查点抑制剂（ICI）的临床反应。然而,有害生态失调没有一致的定义。基于宏基因组学（MG）对245例非小细胞肺癌（NSCLC）患者粪便进行测序，我们构建了物种水平的共丰度网络,这些网络被聚集成与总体存活相关的物种相互作用组(SIG).37和45个MG物种（MGS）与对ICIs的抗性（SIG1）和反应（SIG2）相关，分别。当与Akkermansia物种的定量相结合时，该程序允许基于人计算拓扑评分(TOPOSCORE),该评分在另外254例NSCLC患者和216例泌尿生殖系统癌症患者中得到验证.最后,该TOPOSCORE被转化为基于21细菌探针集的qPCR评分,该评分在NSCLC患者以及结直肠和黑色素瘤患者的前瞻性队列中得到了验证.这种方法可以代表肠道菌群失调的动态诊断工具，以指导以微生物群为中心的个性化干预措施。
