Association between premature ovarian insufficiency and gut microbiota Original paper

What was studied?

This original research article examined the vaginal microbiome in premature ovarian insufficiency, exploring how microbial imbalances relate to hormonal disruptions characteristic of POI. Using 16S rRNA sequencing of vaginal samples, the investigators compared microbial composition, diversity, and predicted metabolic activity between affected women and healthy controls. The study sought to determine whether distinct microbial signatures were associated with POI and whether specific taxa correlated with reproductive hormone levels. By integrating microbial profiling with detailed endocrine assessments, the authors aimed to clarify whether alterations in the vaginal ecosystem may influence, reflect, or even contribute to ovarian dysfunction. The findings help establish foundational microbial patterns that could support future diagnostic or mechanistic research.

Who was studied?

The study analysed 40 women aged 24–40 years recruited from Shenzhen Maternity and Child Healthcare Hospital: 28 with spontaneous POI and 12 healthy women matched for age and BMI. Strict exclusion criteria removed confounding influences such as recent antibiotic use, autoimmune disease, pregnancy, pelvic surgery, gastrointestinal disorders, abnormal BMI, smoking, or cancer therapy. POI participants met diagnostic criteria of amenorrhoea for at least four months and repeatedly elevated follicle-stimulating hormone (FSH) levels exceeding 40 IU/L. Controls demonstrated regular menstrual cycles and normal ovarian hormone profiles. Vaginal and blood samples were collected, enabling paired microbiome–hormone comparisons essential for interpreting microbe–host interactions.

Most important findings

Women with POI showed significantly altered vaginal microbial composition, diversity, and functional patterns compared with healthy controls. Increased beta diversity (weighted UniFrac) reflected greater community instability, also evident in the genus-level shifts visualised in the bar plots on pages 4–5. Lactobacillus—a hallmark of healthy vaginal ecology—was markedly reduced (54.18% vs 83.94%). Genera associated with dysbiosis, including Gardnerella, Prevotella, Anaerococcus, Peptoniphilus, Veillonella, and especially Streptococcus, were substantially elevated. Linear discriminant analysis highlighted significantly lower Lactobacillus, Odoribacter, and Brevundimonas in POI, while Streptococcus was significantly higher. Microbe–hormone correlations (heatmap on page 5) showed Lactobacillus positively associated with estradiol and negatively with FSH, mirroring menopausal-like hormonal shifts. Brevundimonas and Odoribacter correlated positively with AMH, while Streptococcus correlated positively with FSH and LH, reinforcing its association with ovarian insufficiency. Functional pathway analysis revealed metabolic alterations, with 15 pathways enriched in POI, including purine and pyrimidine biosynthesis routes, suggesting potential links to cellular stress or DNA damage. Lactose and galactose degradation pathways were reduced, implying possible galactose accumulation, a known ovarian toxin.

Key implications

The findings underscore a clear association between POI and vaginal microbial dysbiosis, characterised by depleted Lactobacillus dominance, increased inflammatory or opportunistic taxa, and hormonally relevant microbial shifts. These microbiome patterns resemble postmenopausal transitions, suggesting that hormonal decline may destabilise protective microbial structures, while microbial changes may further influence endocrine pathways. The study supports the concept of the vagina–ovary axis, where microbial metabolites, immune activation, or disrupted carbohydrate metabolism could contribute to impaired follicular function. While causal mechanisms require further investigation, this microbial signature has potential value for diagnostic development, early risk detection, and future probiotic or microbiome-targeted interventions.

Citation

Wu J, Ning Y, Tan L, Chen Y, Huang X, Zhuo Y. Characteristics of the vaginal microbiome in women with premature ovarian insufficiency. Journal of Ovarian Research. 2021;14:172