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*, Dao Ming Wang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
19 Downloads (Pure)

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.

Original languageEnglish
Article number7421
Number of pages12
JournalNature Communications
Volume14
DOIs
Publication statusPublished - Nov-2023

Keywords

  • Data mining
  • Microbial genetics
  • Tumour immunology

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