Gut Microbial Diversity in Women With Polycystic Ovary Syndrome Correlates With Hyperandrogenism

Abstract

Context: A majority of women with polycystic ovary syndrome (PCOS) have metabolic abnormalities that result in an increased risk of developing type 2 diabetes and heart disease. Correlative studies have shown an association between changes in the gut microbiome and metabolic disorders. Two recent studies reported a decrease in α diversity of the gut microbiome in women with PCOS compared with healthy women.

Objective: We investigated whether changes in the gut microbiome correlated with specific clinical parameters in women with PCOS compared with healthy women. We also investigated whether there were changes in the gut microbiome in women with polycystic ovarian morphology (PCOM) who lacked the other diagnostic criteria of PCOS.

Participants: Subjects were recruited at the Poznan University of Medical Sciences. Fecal microbial diversity profiles of healthy women (n = 48), women with PCOM (n = 42), and women diagnosed with PCOS using the Rotterdam criteria (n = 73) were analyzed using 16S ribosomal RNA gene sequencing.

Results: Lower α diversity was observed in women with PCOS compared with healthy women. Women with PCOM had a change in α diversity that was intermediate between that of the other two groups. Regression analyses showed that hyperandrogenism, total testosterone, and hirsutism were negatively correlated with α diversity. Permutational multivariate analysis of variance in UniFrac distances showed that hyperandrogenism was also correlated with β diversity. A random forest identified bacteria that discriminated between healthy women and women with PCOS.

Conclusion: These results suggest that hyperandrogenism may play a critical role in altering the gut microbiome in women with PCOS.

Figure 1.

Biodiversity of the gut microbiome was decreased in women with PCOS. Box plots of α diversity in fecal samples from healthy women (controls; n = 47), women with PCOM (n = 41), and women diagnosed with PCOS using the Rotterdam criteria (n = 70) are shown, with whiskers extending 1.5× past the interquartile range. (a‒d) α diversity was calculated using (a) the number of observed SVs as an estimate of species richness, (b) Faith PD as an estimate of species richness that takes phylogenetic relationships into account, (c) Shannon as an estimate of both species richness and evenness, and (d) Pielou as an estimate of the evenness of a community. One-way analysis of variance was performed on ranked data with the Tukey honest significant difference post hoc test to compare means among groups. *P < 0.05.

Figure 2.

A decrease in gut bacterial biodiversity correlated with an increase in testosterone level and hirsutism. (a‒d) Scatterplots and trend lines show the relationship between testosterone and (a) observed SVs or (c) Faith PD as well as the relationship between hirsutism and (b) observed SVs or (d) Faith PD. Results of a Pearson correlation (P value and correlation coefficient) are shown in the insets, with the gray shaded areas indicating the 95% confidence interval for the line of best fit. Healthy women (controls; n = 47), women with PCOM (n = 41), and women with PCOS (n = 70).

Figure 3.

β diversity of the gut bacterial community was influenced by hyperandrogenism (HA), and random forests identified bacterial taxa that distinguished between healthy women and women with PCOS. (a) PCoA of β diversity (unweighted UniFrac distances) of fecal samples from healthy women (controls; n = 43) and women with PCOS (n = 66). Proportion of variance explained by each principal coordinate (PC) axis is denoted on the corresponding axis. Permutation analysis of variance of the unweighted UniFrac distances indicated that hyperandrogenism had a strong influence on the gut microbial community (P = 0.0009). (b) CCA represents the relationship between β diversity and specific variables of interest, such as HA, testosterone, and hirsutism. CCA demonstrated that changes in the gut microbial communities between healthy women and women with PCOS correlated with hirsutism (permutation test; P = 0.06). Proportion of variance explained by each CCA axis is denoted on the corresponding axis. The arrows represent the direction and strength of the correlation between gut microbiome composition and specific variables of interest. (c) A random forest classifier was used to identify bacterial observed SVs that best distinguished between healthy women (controls) and women with PCOS. The relative mean abundances (mean ± standard error of the mean) of the top eight most discriminant observed SVs are identified to the genus and species level when possible.