Blood metabolites reflect the effect of gut microbiota on differentiated thyroid cancer: a Mendelian randomization analysis

Background Studies have linked gut microbiome and differentiated thyroid cancer (DTC). However, their causal relationships and potential mediating factors have not been well defined. Our study investigated the causal relationships between the gut microbiome, papillary thyroid cancer (PTC) and follic...

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Veröffentlicht in:BMC cancer Jg. 25; H. 1; S. 368 - 10
Hauptverfasser: Zhang, Hanfei, Li, Yuhao, Li, Lin
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 28.02.2025
BioMed Central Ltd
Springer Nature B.V
BMC
Schlagworte:
Adenocarcinoma, Follicular - blood
Adenocarcinoma, Follicular - genetics
Adenocarcinoma, Follicular - microbiology
Adenocarcinoma, Follicular - pathology
Bayes Theorem
Bayesian analysis
Biomedical and Life Sciences
Biomedicine
Blood
Blood metabolites
Cancer Research
Causes of
Development and progression
Follicular thyroid cancer
Gastrointestinal Microbiome
Gastrointestinal system
Genome-wide association studies
Genome-Wide Association Study
Genomes
Gut Microbiota
Health aspects
Health Promotion and Disease Prevention
Humans
Intestinal microflora
Medicine/Public Health
Mendelian randomization
Mendelian Randomization Analysis
Metabolic Networks and Pathways
Metabolic pathways
Metabolism
Metabolites
Microbiomes
Microbiota
Microbiota (Symbiotic organisms)
Oncology
Papillary thyroid cancer
Physiological aspects
Sensitivity analysis
Sphingomyelin
Statistical analysis
Statistics
Surgical Oncology
Thyroid cancer
Thyroid Cancer, Papillary - blood
Thyroid Cancer, Papillary - genetics
Thyroid Cancer, Papillary - microbiology
Thyroid Cancer, Papillary - pathology
Thyroid Neoplasms - blood
Thyroid Neoplasms - genetics
Thyroid Neoplasms - microbiology
Thyroid Neoplasms - pathology
China
Mendelian randomization
Papillary thyroid cancer
Follicular thyroid cancer
Gut Microbiota
Blood metabolites
ISSN:1471-2407, 1471-2407
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Zusammenfassung:Background Studies have linked gut microbiome and differentiated thyroid cancer (DTC). However, their causal relationships and potential mediating factors have not been well defined. Our study investigated the causal relationships between the gut microbiome, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC), as well as the mediating effect of potential blood metabolites, using genetic approaches. Methods Leveraging the summary statistics of gut microbial taxa, blood metabolites, PTC and FTC from the largest genome-wide association studies (GWAS) to date, we applied the bidirectional and mediation Mendelian randomization (MR) design. The multivariable MR approach based on Bayesian model averaging (MR-BMA) was used to prioritize the most likely causal taxa. Furthermore, metabolic pathway analysis was performed via the web-based Metaconflict 4.0. Results After sensitivity analyses, we identified 4 taxa, 19 blood metabolites, and 5 gut bacterial pathways were causally associated with PTC. Similarly, 3 taxa, 31 blood metabolites, and 3 gut bacterial pathways were found to be causally associated with FTC, with 2 blood metabolites exhibiting bidirectional causal relationships. Metabolic pathway analysis revealed 8 significant pathways in PTC and FTC. MR-BMA analysis pinpointed species Bifidobacterium longum as the primary causal taxon for PTC and genus Bacteroides for FTC. The mediation MR analysis showed that sphingomyelin (d18:2/23:0, d18:1/23:1, d17:1/24:1) and 2-hydroxysebacate mediated the causal effects of specific gut microbiota on PTC and FTC, respectively. Conclusion The study suggested a causal relationship between several gut microbial taxa and DTC, and that specific blood metabolites might mediate this relationship.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1471-2407
1471-2407
DOI:10.1186/s12885-025-13598-y