THE ROLE OF GUT MICROBIOTA IN GYNECOLOGICAL DISORDERS: A NOVEL AREA OF RESEARCH

Abstract

Objective: We investigated the relationship between gut microbiota composition and two common gynecological disorders—endometriosis and polycystic ovary syndrome (PCOS)—in women presenting to a tertiary care hospital in Karachi, Pakistan. Building on evidence that dysbiosis and estrobolome activity can modulate estrogen signaling, inflammation, and metabolic homeostasis, we examined whether specific microbial signatures and metabolites differed between patients and controls.

Methods: We conducted a case–control study (January–September 2025) including laparoscopically/histologically confirmed endometriosis cases and Rotterdam-defined PCOS cases, each with age- and BMI-matched gynecologically healthy controls. After standardized dietary and medication washouts, we collected stool samples for 16S rRNA gene sequencing and targeted short-chain fatty acid (SCFA) quantification. Primary outcomes were alpha/beta diversity and differential abundance; secondary outcomes included associations of microbial taxa and SCFAs with clinical phenotypes (pain scores, insulin resistance indices, and androgen levels). Analytical approaches included PERMANOVA for beta diversity and multivariable regression for metabolite–phenotype links, following approaches reported in prior microbiome–PCOS literature.

Results: Compared with controls, women with endometriosis showed lower gut microbial diversity and a higher Firmicutes/Bacteroidetes ratio, with over-representation of taxa previously linked to estrogen recycling (e.g., Escherichia/Shigella) and inflammation. Women with PCOS exhibited higher fecal propionate and enrichment of Prevotella copri, which correlated with insulin resistance indices independent of BMI. The directionality of these signals aligned with recent reports implicating β-glucuronidase–mediated estrogen deconjugation in endometriosis and propionate-linked microbial networks in PCOS.

Conclusion: In this Karachi cohort, gut dysbiosis characterized both endometriosis and PCOS but with disorder-specific features: estrogen-recycling and pro-inflammatory taxa in endometriosis, and propionate-associated, insulin-resistance–linked taxa in PCOS. These findings supported the gut–reproductive axis as a promising avenue for biomarker development and microbiota-targeted interventions in South Asian populations.