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.

肠道微生物群影响癌症患者对免疫检查点抑制剂（ICIs）的临床反应。然而，对于有害的生态失调还没有达成共识的定义。基于对 245 名非小细胞肺癌 (NSCLC) 患者粪便的宏基因组 (MG) 测序，我们构建了物种水平的共丰度网络，该网络被聚类为与总体生存相关的物种相互作用组 (SIG)。 37 种和 45 种 MG 物种 (MGS) 分别与 ICI 的耐药性 (SIG1) 和反应性 (SIG2) 相关。当与 Akkermansia 物种的量化相结合时，该程序允许基于个人的拓扑评分 (TOPOSCORE) 计算，并在另外 254 名 NSCLC 患者和 216 名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 种细​​菌探针组的 qPCR 评分，该评分在 NSCLC 患者以及结直肠癌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。