Gut microbiota and SCFAs improve the treatment efficacy of chemotherapy and immunotherapy in NSCLC.

Journal: NPJ biofilms and microbiomes
Published Date:

Abstract

The role of gut dysbiosis in shaping immunotherapy responses is well-recognized, yet its effect on the therapeutic efficacy of chemotherapy and immunotherapy combinations remains poorly understood. We analyzed gut microbiota in non-small cell lung cancer (NSCLC) patients treated with chemo-immunotherapy, comparing responders and non-responders using 16S rRNA sequencing. Responders showed higher microbial richness and abundance of specific genera like Faecalibacterium and Subdoligranulum, and the phylum Firmicutes. Support vector machine (SVM), a machine learning model based on microbial composition, predicted treatment efficacy with the area under the curve (AUC) values of 0.763 for genera and 0.855 for species. Metagenomic analysis revealed significant differences in metabolic pathways, with responders exhibiting higher short-chain fatty acids (SCFAs) production. Fecal microbiota transplantation (FMT) and SCFAs supplementation in mouse models enhanced treatment efficacy by promoting effector T cell activity in tumors. Our study suggests that gut microbiota, through SCFAs production, regulates chemo-immunotherapy efficacy, offering new strategies to improve NSCLC treatment outcomes.

Authors

  • Yanping Yang
    Shanghai Institute of Infectious Disease and Biosecurity, Fudan University Shanghai 200032 China.
  • Maosong Ye
    Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Yijun Song
    Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Wenyu Xing
    Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai 200438, China; Human Phenome Institute, Fudan University, Shanghai 200438, China.
  • Xing Zhao
    Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People's Republic of China.
  • Yufan Li
    Anhui University of Chinese Medicine, Hefei, China.
  • Jiacheng Shen
    George R. Brown School of Engineering, Rice University, Houston, USA.
  • Jian Zhou
    CTIQ, Canon Medical Research USA, Inc., Vernon Hills, 60061, USA.
  • Kinji Arikawa
    John H Stroger Jr Hospital of Cook County, Chicago, IL, USA.
  • Shengdi Wu
    Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. wu.shengdi@zs-hospital.sh.cn.
  • Yuanlin Song
    Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China; Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai, 200032, China.
  • Nuo Xu
    Information Engineering, Guangdong University of Technology, Guangzhou, China.