Blood Bacterial 16S rRNA Gene Alterations in Women with Polycystic Ovary Syndrome

Background: Evidence proved the association between gut microbiome dysbiosis and polycystic ovary syndrome (PCOS) in metabolic defect, reproductive ability and hyperandrogenism. However, alterations of the blood microbiome of PCOS remained unknown. In this case-control study, we explored the blood microbiome profile of PCOS. Methods: Blood bacterial DNA of 24 PCOS patients and 24 healthy controls were obtained and investigated by 16S rRNA Gene Sequencing using the MiSeq technology. α and β diversity were used to analyze within-sample biodiversity and similarity of one group to another, respectively. Linear discriminant analysis effect size (LEfSe) was calculated to determine biomarkers between groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional prediction was performed at genera level. Findings: α diversity of blood microbiome revealed a significant decrease in women with PCOS, and a major separation in β diversity was observed between groups by weighted UniFac technique. PCOS group demonstrated a significant decrease in the proportion of sequences in Proteobacteria, Firmicutes and Bacteroidetes, and a significant richer abundance in Actinobacteria . Cladogram demonstrated microbiome differences of the two groups at various phylogenic levels. Meanwhile, LDA presented a significant decrease in Burkholderiaceae, Lachnospiraceae, Bacteroidaceae, Ruminococcaceae and S24-7, and a significant increase in Nocardioidaceae and Oxalobacteraceae in PCOS group. KEGG analysis exhibited 14 main pathways with significant differences between two groups at a genera level. Interpretation: Our findings demonstrated a significant lower α diversity, different β diversity and significant taxonomic variations in blood microbiome in PCOS patients compared with healthy controls. Funding: Funding: This work was supported by the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University, China (XJTU1AF-2018-017, XJTU1AF-CRF-2019-002), the Natural Science Basic Research Program of Shaanxi (2018JM7073, 2017ZDJC-11), the Key Research and Development Program of Shaanxi (2017ZDXM-SF-068, 2019QYPY-138), the Innovation Capability Support Program of Shaanxi (2017XT-026, 2018XT-002), and the Medical Research Project of Xi’an Social Development Guidance Plan (2017117SF/YX011-3). Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: This study was conducted in accordance with the ethical standards of the Declaration of Helsinki. The study was approved by the Institutional Review Board of the First Affiliated Hospital of Xi’an Jiao Tong University (IRB No. XJTU1AF2018LSK139) and was registered in Chinese Clinical Trial Registry (ChiCTR-TRC-1800020018).