Higher BMI is associated with vaginal microbiome alterations in women with PCOS.

Abstract: Polycystic ovary syndrome (PCOS) is commonly associated with obesity and metabolic disturbances. Although gut and vaginal microbiome changes have been linked to PCOS, the independent role of body mass index in these alterations remains unclear. This study aimed to compare gut and vaginal microbiomes in women with PCOS and healthy controls, emphasizing the impact of body mass index. Seventy-five women were enrolled, including 55 with PCOS and 20 healthy controls. Participants were stratified into normal-weight (<25) and overweight (≥25) groups. Vaginal and anorectal swabs were analyzed using full-length 16S rRNA nanopore sequencing. Microbial diversity and composition were assessed with alpha diversity indices, principal component analysis, analysis of composition of microbes, PERMANOVA, and vaginal community state type classification. Without body mass index stratification, women with PCOS showed differences in several vaginal taxa compared with healthy controls. Within the PCOS cohort, overweight women exhibited higher vaginal alpha diversity, reduced Lactobacillus dominance, and enrichment of anaerobic taxa compared with normal-weight women with PCOS. Differences in vaginal microbial composition were also observed between healthy and PCOS women with normal body mass index. In contrast, gut microbiome alterations were limited and less consistent across analytical approaches. Vaginal community state type analysis revealed predominance of class IV communities in both healthy women and women with PCOS. These findings suggest that higher body mass index is associated with vaginal microbiome alterations in women with PCOS, although PCOS-related factors independent of body weight may also contribute to the observed microbial differences. Lay summary: Polycystic ovary syndrome is a common condition that affects hormones, fertility, and metabolism in women. Many women with this condition are also overweight, but it is not fully understood how body weight influences the bacteria living in the body. In this study, we compared bacteria present in vaginal and anorectal samples from women with and without polycystic ovary syndrome, while also considering body weight. We found that women with higher body weight had more noticeable changes in vaginal bacterial composition, including lower amounts of protective Lactobacillus bacteria and higher diversity of anaerobic bacteria. At the same time, some bacterial differences were also observed in women with polycystic ovary syndrome who had normal body weight. Changes in gut bacteria were smaller and less consistent. These findings suggest that both body weight and polycystic ovary syndrome may influence vaginal bacterial composition and should be considered in future studies of women's reproductive health.