AUTHOR=Yang Hua 

TITLE=The causality between gut microbiota and endometriosis: a bidirectional Mendelian randomization study

JOURNAL=Frontiers in Medicine

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1434582

DOI=10.3389/fmed.2024.1434582

ISSN=2296-858X

ABSTRACT=<sec><title>Background</title><p>Observational studies and animal experiments had suggested a potential relationship between gut microbiota abundance and pathogenesis of endometriosis (EMs), but the relevance of this relationship remains to be clarified.</p></sec><sec><title>Methods</title><p>We perform a two-sample bidirectional Mendelian randomization (MR) analysis to explore whether there is a causal correlation between the abundance of the gut microbiota and EMs and the direction of causality. Genome-wide association study (GWAS) data ukb-d-N80, finn-b-N14-EM, and MiBinGen were selected. Inverse variance weighted (IVW), weighted median, and MR Egger are selected for causal inference. The Cochran Q test, Egger intercept test, and leave-one-out analysis are performed for sensitivity analyses.</p></sec><sec><title>Results</title><p>In the primary outcome, we find that a higher abundance of class Negativicutes, genus <italic>Dialister</italic>, genus <italic>Enterorhabdus</italic>, genus <italic>Eubacterium</italic> xylanophilum group, genus <italic>Methanobrevibacter</italic> and order Selenomonadales predict a higher risk of EMs, and a higher abundance of genus <italic>Coprococcus</italic> and genus <italic>Senegalimassilia</italic> predict a lower risk of EMs. During verifiable outcomes, we find that a higher abundance of phylum Cyanobacteria, genus <italic>Ruminococcaceae</italic> UCG002, and genus <italic>Coprococcus</italic> 3 predict a higher risk of EMs, and a higher abundance of genus <italic>Flavonifracto</italic>, genus <italic>Bifidobacterium</italic>, and genus <italic>Rikenellaceae</italic> RC9 predict a lower risk of EMs. In primary reverse MR analysis, we find that EMs predict a lower abundance of the genus <italic>Eubacterium</italic> fissicatena group, genus <italic>Prevotella7</italic>, genus <italic>Butyricicoccus</italic>, family <italic>Lactobacillaceae</italic>, and a higher abundance of genus <italic>Ruminococcaceae</italic> UCG009. In verifiable reverse MR analysis, we find that EMs predict a lower abundance of the genus <italic>Ruminococcaceae</italic> UCG004 and a higher abundance of the genus <italic>Howardella</italic>.</p></sec><sec><title>Conclusion</title><p>Our study implies a mutual causality between gut microbiota abundance and the pathogenesis of EMs, which may provide a novel direction for EMs diagnosis, prevention, and treatment, may promote future functional or clinical analysis.</p></sec>