Bidirectional Causal Effect Between Gut Microbiota and Glioma Risk: A Systematic
Review-Based Mendelian Randomization and Immune-Mediated Effect Analysis
#MMPMID41384027
Wang J
; Zhang Y
; Kang Z
; Li S
; Zhang R
; Huang M
; Wang C
; Fan Y
; Liu X
; Chen Y
; Han T
; Wang Y
; Li W
Cancer Innov
2025[Dec]; 4
(6
): e70039
PMID41384027
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BACKGROUND: Glioma is the most common malignant tumor in the central nervous
system, with unclear pathogenesis and poor treatment outcomes. Recent research
reveals that the brain-gut axis-involving gut microbiota and immune
activity-influences central nervous system tumors. Given the pivotal role of the
brain-gut axis in glioma, our study aimed to elucidate the causal association
between gut microbiota and glioma, and to identify potential immune-mediated
effects and therapeutic targets. METHODS: Based on publicly available genome-wide
association study data, our research employed multi-subgroup, replicated,
Bayesian weighted, and summary statistics-based two-sample Mendelian
randomization (MR) studies, combined with the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) systematic review strategy, to
systematically evaluate the potential causal effects of gut microbiota on glioma
and their immune-mediated traits. RESULTS: The initial screening identified 53
gut microbiota and 58 plasma immune traits with potential causal associations
with glioma. Through external data and systematic review from six studies, we
ultimately confirmed five gut microbiota-plasma immune trait-glioma pathways.
CD28(+)CD45RA(-) CD8dim Treg (OR?=?0.019, p?=?0.007) mediated the risk of
Bacteroides A plebeius A (OR?=?0.149, p?=?0.036) on glioma, accounting for 2.99%
of the effect; the proportion of CD4(+) memory T cells in whole blood
(OR?=?0.066, p?=?0.029) mediated the risk of Bacteroides sp002160055 (OR?=?0.158,
p?=?0.024) on non-glioblastoma(GBM), accounting for 8.51% of the effect, while
the risk of Faecalicoccus (OR?=?0.345, p?=?0.005) on non-GBM was jointly mediated
by the absolute number of Naive CD8br and the expression of CD19 in IgD(+) CD38br
B cells. The protective effect of Faecalibacterium sp002160895 on GBM was
mediated by 7.59% of the expression level of CD4 in Treg cells. CONCLUSION: Our
study, through MR analysis, revealed the causal relationship between gut
microbiota and the susceptibility to glioma, and for the first time proposed the
important role of circulating immune cells in this process, providing new
potential biomarkers for the early diagnosis and treatment of glioma.
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