Core Viewpoint - The article discusses the promising results of fecal microbiota transplantation (FMT) combined with immunotherapy in treating non-small cell lung cancer (NSCLC), melanoma, and metastatic renal cell carcinoma (mRCC), highlighting its potential to overcome resistance to PD-1 therapy and improve patient outcomes [2][3][4]. Group 1: FMT and Immunotherapy in NSCLC and Melanoma - The FMT-LUMINate trial demonstrated an objective response rate (ORR) of 80% (16/20) in NSCLC and 75% (15/20) in melanoma, achieving the primary endpoint [8]. - Safety assessments indicated no grade 3 or higher adverse events in the NSCLC cohort, while 65% of melanoma patients experienced grade 3 or higher adverse events [8]. - The study found that responders had a unique gut microbiome composition post-FMT, with significant reductions in specific bacterial species associated with non-responders [9]. Group 2: FMT in Metastatic Renal Cell Carcinoma - The PERFORM trial showed that 50% (10/20) of mRCC patients experienced grade 3 immune-related adverse events, with no severe FMT-related toxicities reported [11][14]. - The objective response rate was 50% (9/18), including 11% (2/18) achieving complete response, with most responders not experiencing severe immune-related adverse events [14]. - Improvements in gut microbiome diversity were linked to reduced toxicity and enhanced treatment response, while the presence of specific bacteria correlated with higher immune-related adverse events [15][16]. Group 3: FMT Combined with Pembrolizumab and Axitinib - The TACITO trial evaluated the efficacy of donor-derived FMT in mRCC patients receiving pembrolizumab and axitinib, with a primary endpoint of disease progression-free survival [18][21]. - Although the primary endpoint was not met, the donor FMT group showed a significantly longer median progression-free survival of 24.0 months compared to 9.0 months in the placebo group [22]. - The donor FMT group had an ORR of 52%, while the placebo group had 32%, indicating potential benefits of selective donor FMT in enhancing immunotherapy outcomes [22].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 粪菌移植 （FMT） 是一种日益常用的干预手段，通过将 健康人粪便中的微生物移植到病人体内， 以期恢复其肠道菌群的健康平衡。然而，粪便中的微生物主要 是来自结肠 （大肠的一部分） 的 厌氧微生物，这些微生物在 小肠或消化系统的其他部位定植时，可能会导致 肠道生态系统失衡。 实际上，美国 FDA 已经批准了粪菌移植 （FMT） 用于治疗复发性艰难梭菌感染，但其在其他疾病 （包括肥胖症、自闭症、癌症和炎症性肠病） 中的作用机 制、疗效以及脱靶效应仍不清楚。有报道显示，接受 FMT 的患者曾出现过肠胃不适、败血症以及代谢问题 （例如体重增加、溃疡性结肠炎病情加重等） 。 在这项最新研究中，研究团队在接受通过上消化道内镜进行粪菌移植的人类受试者中，观察到在 4 周后十二指肠内厌氧菌定植。研究团队推测，经过口腔的粪菌 移植 （FMT） 会造成宿主-微生物不匹配，从而影响小肠稳态。 为了验证这一点，研究团队给经过抗生素处理的无特定病原体 （SPF） 小鼠分别移植 空肠菌移植 （ JMT ） 、 盲肠菌移植 （ CMT ） 或 粪菌移植 （ FMT ） ，并在 1 个月或 3 个月后 ...