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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Liu, Baike Liu, Zheran Jiang, Tianxiang Gu, Xiangshuai Yin, Xiaonan Cai, Zhaolun Zou, Xiaoqiao Dai, Lei Zhang, Bo |
| 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. |
| Related Links | https://eurjmedres.biomedcentral.com/counter/pdf/10.1186/s40001-024-01741-7.pdf |
| Ending Page | 16 |
| Page Count | 16 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s40001-024-01741-7 |
| Journal | European Journal of Medical Research |
| Issue Number | 1 |
| Volume Number | 29 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-03-12 |
| Access Restriction | Open |
| Subject Keyword | Medicine Public Health Infectious Diseases Internal Medicine Surgery Oncology Biomedicine Lachnospiraceae Akkermansia Ruminiclostridium6 Gut microbiota Immunotherapy toxicity Immune-related adverse effects irAEs Mendelian randomization study Multivariable Mendelian randomization study MVMR Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
| Journal Impact Factor | 2.8/2023 |
| 5-Year Journal Impact Factor | 2.9/2023 |
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