Gut microbial structural variation associates with immune checkpoint inhibitor response

Rong Liu (), You Zou, Wei-Quan Wang, Jun-Hong Chen, Lei Zhang, Jia Feng, Ji-Ye Yin, Xiao-Yuan Mao, Qing Li, Zhi-Ying Luo, Wei Zhang () and Dao-Ming Wang ()
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Rong Liu: Central South University
You Zou: Central South University
Wei-Quan Wang: Central South University
Jun-Hong Chen: Central South University
Lei Zhang: Central South University
Jia Feng: Central South University
Ji-Ye Yin: Central South University
Xiao-Yuan Mao: Central South University
Qing Li: Central South University
Zhi-Ying Luo: Central South University
Wei Zhang: Central South University
Dao-Ming Wang: Department of Genetics

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts’ prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy.

Date: 2023
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DOI: 10.1038/s41467-023-42997-7

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