Gut microbiota biodiversity indices as markers of hyperandrogenemia in women of reproductive age

Introduction. Previously, it was shown that the “classic” phenotypes of polycystic ovarian syndrome (PCOS) are associated with significant decrease in gut microbiota alpha diversity as compared with healthy women.

The aim of the study. To establish cut-off points for alpha diversity indices, significant in polycystic ovarian syndrome with hyperandrogenism.

Material and methods. The manuscript presents a sub-study of Eastern Siberia PCOS Epidemiology and Phenotype Study, conducted in Eastern Siberia (Russia) from 2016 to 2019. All participants (175 women of reproductive age: 26 women with PCOS (according to Rotterdam criteria (2003)) and hyperandrogenemia (increased levels of total testosterone (TT) and/or free androgenindex(FAI), and/ordehydroepiandrosterone sulphate (DHEAS)), 149 – without hyperandrogenemia) were recruited during the annual employment medical assessment. Methods included a questionnaire survey, anthropometry and modified Ferriman – Gallwey score, gynecological examination, pelvic ultrasound, and blood serum tests for TT, DHEAS, sex hormone-binding globulin, FAI, prolactin, thyroid-stimulating hormone, and 17-hydroxyprogesterone. Five indices of alpha diversity (amplicon sequencing variant, Shannon index, Simpson index, Chao index, and abundance-based coverage Index) were estimated for the gut microbiota using amplicon metasequencing. Statistical analysis included ROC-analysis for development of cut-off points for the indices, associated with hyperandrogenism in women of reproductive age with PCOS.

Results. According to results of ROC-analysis, the greatest sensitivity with moderate specificity, with a high area under the curve was established for the Shannon and Simpson indices with cut-off points classifying women with or without hyperandrogenemia – 5.84 and 0.97, respectively.

Conclusions. The developed criteria for assessing alpha diversity using cut-off points for the most significant indices can be useful for monitoring the results of different therapeutic interventions (prebiotics, probiotics, etc.) in hyperandrogenic phenotypes of PCOS.

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