Gut microbial structural variation associates with immune checkpoint inhibitor response.
Rong LiuYou ZouWei-Quan WangJun-Hong ChenLei ZhangJia FengJi-Ye YinXiao-Yuan MaoQing LiZhi-Ying LuoWei ZhangDao-Ming WangPublished in: Nature communications (2023)
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.
Keyphrases
- free survival
- clinical trial
- end stage renal disease
- microbial community
- healthcare
- ejection fraction
- copy number
- randomized controlled trial
- newly diagnosed
- chronic kidney disease
- systematic review
- escherichia coli
- prognostic factors
- peritoneal dialysis
- gene expression
- patient reported outcomes
- combination therapy
- open label
- genetic diversity
- double blind