Multi-omics of the gut microbial ecosystem in patients with microsatellite-instability-high gastrointestinal cancer resistant to immunotherapy

• DOI: 10.1016/j.xcrm.2023.101355
• Publication Date: 2024-01-08T15:41:58Z
• Authors: Siyuan Cheng; Zihan Han; Die Dai; Fang Li; Xiaotian Zhang; Ming Lu; Zhihao Lu; Xicheng Wang; Jun Zhou; Jian Li; Xiaohuan Guo; Panwei Song; Chuangzhao Qiu; Wei Shen; Qi Zhang; Ning Zhu; Xi Wang; Yan Tan; Yan Kou; Xiaochen Yin; Lin Shen; Zhi Peng
• Keywords: Microsatellite Instability; Metabolome; Omics; Gut microbiome

Despite the encouraging efficacy of anti-PD-1/PD-L1 immunotherapy in microsatellite-instability-high/deficient mismatch repair (MSI-H/dMMR) advanced gastrointestinal cancer, many patients exhibit primary or acquired resistance. Using multi-omics approaches, we interrogate gut microbiome, blood metabolome, and cytokines/chemokines with MSI-H/dMMR cancer (N = 77) at baseline during treatment. We identify a number microbes (e.g., Porphyromonadaceae) metabolites arginine) highly associated resistance to immunotherapy. An independent validation cohort 39) mouse model are used further confirm our findings. A predictive machine learning for is also built achieves an accuracy 0.79 on external set. Furthermore, several pinpointed that gradually changed process In summary, study demonstrates essential role microbiome drug resistance, this can be utilized as preventative diagnosis tool therapeutic target future.