Causal association between gut microbiome and polycystic ovary syndrome: A bidirectional Mendelian randomization...

Area of Science:

• Genetics and Microbiology
• Reproductive Endocrinology

Background:

• Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with multifactorial etiology.
• The gut microbiome's role in PCOS pathogenesis is increasingly recognized but causal relationships remain unclear.

Purpose of the Study:

• To elucidate the causal relationship between gut microbiome composition and PCOS using a bidirectional Mendelian randomization approach.
• To identify specific bacterial taxa that may act as protective or risk factors for PCOS.

Main Methods:

• Bidirectional Mendelian randomization (MR) study utilizing summary statistics from the FinnGen consortium (27,943 PCOS cases, 162,936 controls).
• Primary analysis employed the inverse-variance weighting (IVW) method, with sensitivity analyses using MR-Egger, weighted median, and weighted mode methods.
• Reverse MR analyses were conducted to assess the impact of PCOS on gut microbiome composition.

Main Results:

• The genera Streptococcus and Enterorhabdus were found to be protective against PCOS.
• The phylum Tenericutes, and genera Anaerofilum, Coprococcus 2, Lachnospiraceae ND3007 group, and Ruminiclostridium 5 were identified as risk factors for PCOS.
• Reverse MR indicated down-regulation of Tenericutes, Actinobacteria, and specific genera post-PCOS onset, while Bacteroides, Barnesiella, and others were up-regulated.

Conclusions:

• A significant causal relationship exists between the gut microbiome and PCOS.
• Specific bacterial taxa demonstrate potential as biomarkers for targeted diagnosis and therapeutic interventions in PCOS management.