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. 2024 Jul 3:15:1403316.
doi: 10.3389/fmicb.2024.1403316. eCollection 2024.

Dissecting causal relationships between gut microbiota, blood metabolites, and glioblastoma multiforme: a two-sample Mendelian randomization study

Xuan Chen  1 , Lihui Han  1 , Wenzhe Xu  2   3
Affiliations

Dissecting causal relationships between gut microbiota, blood metabolites, and glioblastoma multiforme: a two-sample Mendelian randomization study

Xuan Chen et al. Front Microbiol. .

Abstract

Background: Given the increasing interest in the role of gut microbiota in glioblastoma multiforme (GBM), our objective was to examine the potential causal relationship between gut microbiota and GBM, as well as the mediating effects of specific metabolites.

Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the associations between 196 microbial taxa and GBM. A two-step MR technique was used to identify significant mediators in this relationship. Subsequently, a mediation analysis was performed to explore and quantify the mediating effects of specific metabolites on the causal relationship between gut microbiota and GBM.

Results: Five taxa showed significant associations with GBM. Among them, family Victivallaceae [odds ratio (OR): 1.95; 95% confidence interval (CI): 1.21, 3.13; p = 0.005] and genus Lactococcus (OR: 1.81; 95% CI: 1.04, 3.15; p = 0.036) were positively correlated with the risk of GBM, while phylum Cyanobacteria had a protective effect against GBM (OR: 0.45; 95% CI: 0.22, 0.89; p = 0.021). The mediation analysis revealed that the connections among family Victivallaceae, genus Lactococcus, phylum Cyanobacteria and GBM were mediated by Methyl-4-hydroxybenzoate sulfate, phosphoethanolamine and dehydroepiandrosterone sulfate. Each of these accounted for 7.27, 7.98, and 8.65%, respectively.

Conclusion: Our study provides evidence supporting a potential causal association between certain gut microbiota taxa and GBM. The study highlights the central role of gut microbiota in GBM pathogenesis and their interactions with vital serum metabolites. This paves the way for potential novel therapeutic interventions in GBM management.

Keywords: Mendelian randomization; glioblastoma; gut microbiota; gut-brain axis; metabolites.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Diagrams illustrating associations examined in this study. The total effect (β) was decomposed into: (i) indirect effect (β1 × β2) (where β1 is the effect of gut microbiota on metabolite, and β2 is the effect of metabolite on GBM) and (ii) direct effect (β-β1 × β2). Mediated proportion was the indirect effect divided by the total effect. (B) Flow chart outlining the methodology used to investigate the relation between gut microbiota and GBM. Mediation analysis evaluated the potential influence of M-4-HBS, PE and DHEAS on the microbiota-GBM association.
Figure 2
Figure 2
Forest plot to visualize the relationship between specific gut microbial taxa (exposure) and GBM (outcome).
Figure 3
Figure 3
MR analysis: Microbiota’s effect on mediators and mediators’ on GBM. (A) Forest plot to visualize the effect between microbial taxa and specific mediators. (B) Forest plot exhibiting the causal effect of mediators on GBM.
See this image and copyright information in PMC

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