Mendelian randomization study of the role of TD CD4+ T cells in the association between Streptococcus thermophilus and esophageal cancer.

2026-01-16
Medicine 105(3)
- Yonglun Zhang
- Qian Li

PubMed: 41560008
DOI: 10.1097/md.0000000000047174

Study Design

Type: Observational
Population: 619 EC cases and 314,193 controls in the FinnGen R10 cohort, together with genome-wide association summary statistics of 412 gut microbiota taxa and 731 immune phenotypes
Methods: A 2-sample Mendelian randomization analysis was performed using data from the FinnGen R10 cohort and GWAS summary statistics; mediation analysis was used to explore immune cell-mediated pathways

Esophageal cancer (EC) remains a major global health burden, and emerging research highlights the potential influence of the gut microbiome on its pathogenesis. However, the causal relationship between specific microbial taxa and EC, as well as the immunological mechanisms mediating these effects, remains unclear. A 2-sample Mendelian randomization analysis was performed using data from 619 EC cases and 314,193 controls in the FinnGen R10 cohort, together with genome-wide association summary statistics of 412 gut microbiota taxa and 731 immune phenotypes obtained from the National Human Genome Research Institute-European Bioinformatics Institute Genome-Wide Association Studies Catalog. The analysis aimed to determine causal links between the gut microbiome and EC, and to explore immune cell-mediated pathways through mediation analysis. The results revealed a significant protective association between Streptococcus thermophilus and EC risk (odds ratio = 0.586, 95% confidence interval = 0.402-0.855, P = .006). Mediation analysis indicated that terminally differentiated CD4+ T cells partially mediated this relationship, accounting for approximately 6% of the total effect. This study identifies Streptococcus thermophilus as a potentially protective gut commensal that may reduce EC risk through immune modulation. The findings provide novel insights into microbiome-immune-cancer interactions and suggest possible preventive or therapeutic targets for EC.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Streptococcus thermophilus	—	Reduced Cancer Risk	Beneficial	Moderate	View source The results revealed a significant protective association between Streptococcus thermophilus and EC risk (odds ratio = 0.586, 95% confidence interval = 0.402-0.855, P = .006).