Univariable and multivariable Mendelian randomization study identified the key role of gut microbiota in immunotherapeutic toxicity.
Eur J Med Res
; 29(1): 161, 2024 Mar 12.
Article
em En
| MEDLINE
| ID: mdl-38475836
ABSTRACT
BACKGROUND:
In cancer patients receiving immune checkpoint inhibitors (ICIs), there is emerging evidence suggesting a correlation between gut microbiota and immune-related adverse events (irAEs). However, the exact roles of gut microbiota and the causal associations are yet to be clarified.METHODS:
To investigate this, we first conducted a univariable bi-directional two-sample Mendelian randomization (MR) analysis. Instrumental variables (IVs) for gut microbiota were retrieved from the MiBioGen consortium (18,340 participants). GWAS summary data for irAEs were gathered from an ICIs-treated cohort with 1,751 cancer patients. Various MR analysis methods, including inverse variance weighted (IVW), MR PRESSO, maximum likelihood (ML), weighted median, weighted mode, and cML-MA-BIC, were used. Furthermore, multivariable MR (MVMR) analysis was performed to account for possible influencing instrumental variables.RESULTS:
Our analysis identified fourteen gut bacterial taxa that were causally associated with irAEs. Notably, Lachnospiraceae was strongly associated with an increased risk of both high-grade and all-grade irAEs, even after accounting for the effect of BMI in the MVMR analysis. Akkermansia, Verrucomicrobiaceae, and Anaerostipes were found to exert protective roles in high-grade irAEs. However, Ruminiclostridium6, Coprococcus3, Collinsella, and Eubacterium (fissicatena group) were associated with a higher risk of developing high-grade irAEs. RuminococcaceaeUCG004, and DefluviitaleaceaeUCG011 were protective against all-grade irAEs, whereas Porphyromonadaceae, Roseburia, Eubacterium (brachy group), and Peptococcus were associated with an increased risk of all-grade irAEs.CONCLUSIONS:
Our analysis highlights a strong causal association between Lachnospiraceae and irAEs, along with some other gut microbial taxa. These findings provide potential modifiable targets for managing irAEs and warrant further investigation.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Clostridiales
/
Microbioma Gastrointestinal
/
Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article