Causal relationship between gut microbiota and polycystic ovary syndrome: a literature review and Mendelian randomization study

Abstract

IntroductionNumerous studies have suggested an association between gut microbiota and polycystic ovarian syndrome (PCOS). However, the causal relationship between these two factors remains unclear.MethodsA review of observational studies was conducted to compare changes in gut microbiota between PCOS patients and controls. The analysis focused on four levels of classification, namely, phylum, family, genus, and species/genus subgroups. To further investigate the causal relationship, Mendelian randomization (MR) was employed using genome-wide association study (GWAS) data on gut microbiota from the MiBioGen consortium, as well as GWAS data from a large meta-analysis of PCOS. Additionally, a reverse MR was performed, and the results were verified through sensitivity analyses.ResultsThe present review included 18 observational studies that met the inclusion and exclusion criteria. The abundance of 64 gut microbiota taxa significantly differed between PCOS patients and controls. Using the MR method, eight bacteria were identified as causally associated with PCOS. The protective effects of the genus Sellimonas on PCOS remained significant after applying Bonferroni correction. No significant heterogeneity or horizontal pleiotropy was found in the instrumental variables (IVs). Reverse MR analyses did not reveal a significant causal effect of PCOS on gut microbiota.ConclusionThe differences in gut microbiota between PCOS patients and controls vary across observational studies. However, MR analyses identified specific gut microbiota taxa that are causally related to PCOS. Future studies should investigate the gut microbiota that showed significant results in the MR analyses, as well as the underlying mechanisms of this causal relationship and its potential clinical significance.

Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics

“…The change in gut microbiota might be the result and the cause of the PCOS phenotype. Moreover, amelioration of gut microbiota might improve the PCOS phenotype ( Starling, 2021 ; Salehi et al, 2024 ; Sun et al, 2024 ).…”

Reducing the Risk of Pre-Eclampsia in Women with Polycystic Ovary Syndrome Using a Combination of Pregnancy Screening, Lifestyle, and Medical Management Strategies

“…Preliminary data showed elevated LPS, LPS-binding protein, and zonulin levels, and a beneficial effect of probiotics and synbiotics. A subsequent review of 18 observational studies found a significant difference in 64 gut microbiota taxa between women with PCOS and controls [ 212 ]. A recent meta-analysis of microbiota studies reported that there are specific microbial communities closely associated with PCOS [ 213 ].…”

“…In addition to these observational data, four recent Mendelian randomization studies have investigated a possible causal relationship between the gut microbiome and PCOS. Three studies concluded that there was a causal relationship [ 212 , 213 , 216 ], and one study did not support a causal relationship [ 217 ]. In summary, accumulating evidence supports a role for the gut microbiome in the pathogenesis of PCOS via a variety of possible mechanisms.…”

Unraveling intestinal microbiota’s dominance in polycystic ovary syndrome pathogenesis over vaginal microbiota

“…A large number of studies have found that intestinal flora and its metabolites have the potential to regulate the hypothalamic-pituitary axis and luteinizing hormone secretion through the gut axis, and that the imbalance of intestinal microbiota is associated with HA, insulin resistance, chronic inflammation, and metabolic disorders related to PCOS ( Guo et al., 2023 ; Sun et al., 2024 ). Studies reveal a reduced relative abundance of Lactobacillus , Ruminococcus , and Clostridium , coupled with elevated Prevotella levels, in the intestines of PCOS-afflicted rats ( Guo et al., 2016 ).…”