免疫检查点抑制剂（ICIs）彻底改变了癌症治疗，但其应用受免疫相关不良事件的限制。肠道菌群在免疫治疗反应和毒性中发挥重要作用，而法氏拟梭菌（F. prausnitzii）已证明具有免疫调节潜力。本文发现，接受ICIs并发结肠炎的患者F. prausnitzii的丰度较低。我们通过给予对ICIs敏感的小鼠和移植了人类外周血单个核细胞的免疫缺陷NSG小鼠葡甘露聚糖硫酸钠处理并给予ICIs治疗，研究了ICI引起的结肠炎。双重CTLA-4和PD-1阻断加重了自身免疫性结肠炎，激活了炎症反应，并促进了骨髓细胞浸润，其中包括更高百分比的巨噬细胞、树突状细胞、单核细胞和中性粒细胞。F. prausnitzii的给予减轻了由ICIs引起的加重结肠炎。同时，F. prausnitzii增强了ICIs在携带肿瘤的小鼠中引发的抗肿瘤免疫反应，同时消除了结肠炎。此外，F. prausnitzii的给予增加了肠道微生物的α多样性，并调节了微生物组成，增加了一些肠道益生菌的种群，减少了可能的肠道病原菌。F. prausnitzii在出现ICI相关性结肠炎的小鼠中丰度减少。总之，本研究表明，F. prausnitzii的给予可以改善ICI引起的结肠炎，重塑肠道微生物组成，并增强免疫治疗的抗肿瘤活性。

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy; however, their application is limited by the occurrence of immune-related adverse events. The gut microbiota plays important roles in the response to and toxicity of immunotherapy, and Faecalibacterium prausnitzii (F. prausnitzii) has been shown to possess immunomodulatory potential. Here, we found that patients receiving ICIs who developed colitis had a lower abundance of F. prausnitzii. In vivo, immunocompetent mice administered with dextran sodium sulfate and immunodeficient NSG mice with human peripheral blood mononuclear cell transfer were treated with ICIs to study ICI-induced colitis. Dual CTLA-4 and PD-1 blockade exacerbated autoimmune colitis, activated an inflammatory response, and promoted myeloid cell infiltration, with higher percentages of macrophages, dendritic cells, monocytes, and neutrophils. F. prausnitzii administration mitigated the exacerbated colitis induced by ICIs. Concomitantly, F. prausnitzii enhanced the anti-tumor immunity elicited by ICIs in tumor-bearing mice while abrogating colitis. In addition, administration of F. prausnitzii increased gut microbial alpha diversity and modulated the microbial composition, increasing a subset of gut probiotics and decreasing potential gut pathogens. F. prausnitzii abundance was reduced in mice that developed ICI-associated colitis. Together, this study shows that F. prausnitzii administration ameliorates ICI-induced colitis, reshapes the gut microbial composition, and enhances the anti-tumor activity of immunotherapy.