Gut microbiome causal impacts on the prognosis of breast cancer: a Mendelian randomization study.

ABSTRACT

BACKGROUND: Growing evidence has shown that gut microbiome composition is associated with breast cancer (BC), but the causality remains unknown. We aimed to investigate the link between BC prognosis and the gut microbiome at various oestrogen receptor (ER) statuses. METHODS: We performed a genome-wide association study (GWAS) to analyse the gut microbiome of BC patients, the dataset for which was collected by the Breast Cancer Association Consortium (BCAC). The analysis was executed mainly via inverse variance weighting (IVW); the Mendelian randomization (MR) results were verified by heterogeneity tests, sensitivity analysis, and pleiotropy analysis. RESULTS: Our findings identified nine causal relationships between the gut microbiome and total BC cases, with ten and nine causal relationships between the gut microbiome and ER-negative (ER-) and ER-positive (ER+) BC, respectively. The family Ruminococcaceae and genus Parabacteroides were most apparent among the three categories. Moreover, the genus Desulfovibrio was expressed in ER- BC and total BC, whereas the genera Sellimonas, Adlercreutzia and Rikenellaceae appeared in the relationship between ER + BC and total BC. CONCLUSION: Our MR inquiry confirmed that the gut microbiota is causally related to BC. This further explains the link between specific bacteria for prognosis of BC at different ER statuses. Considering that potential weak instrument bias impacts the findings and that the results are limited to European females due to data constraints, further validation is crucial.