ArticleEuropean journal of medical research2024
Univariable and multivariable Mendelian randomization study identified the key role of gut microbiota in immunotherapeutic toxicity.
Article in European journal of medical research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Beyond just correlation: causal machine learning for the microbiome, from prediction to health policy with econometric tools.Frontiers in microbiology · 2025Pooled it
- Harnessing the microbiome: a new frontier in lung cancer immunotherapy.Cancer biology & medicine · 2026Review
- Harnessing the Microbiome in Cancer Immunotherapy: Regulation, Prediction, and Therapeutic Targeting.Annual review of immunology · 2026Review
- Article
- Gut microbiota diversity is prognostic in metastatic hormone receptor-positive breast cancer patients receiving chemotherapy and immunotherapy.Molecular oncology · 2026Article
- Omics-based biomarkers of immune-related organ toxicities associated with immune checkpoint inhibitors: a scoping review and evidence map.Frontiers in immunology · 2026Article
- Traditional Chinese medicine and its components effectively reduce resistance mediated by immune checkpoint inhibitors.Frontiers in immunology · 2024Review
- Assessing causal relationships between gut microbiota and abortion: evidence from two sample Mendelian randomization analysis.Frontiers in endocrinology · 2024Article
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Authors and funding
9 authors.
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Abstract
backgroundIn 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.
methodsTo 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.
resultsOur 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.
conclusionsOur 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.
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