Impact of Short-Term Isoflavone Intervention in Polycystic Ovary Syndrome (PCOS) Patients on Microbiota Composition and Metagenomics

Abstract

Background: Polycystic ovary syndrome (PCOS) affects 5–20% of women of reproductive age worldwide and is associated with disorders of glucose metabolism. Hormone and metabolic signaling may be influenced by phytoestrogens, such as isoflavones. Their endocrine effects may modify symptom penetrance in PCOS. Equol is one of the most active isoflavone metabolites, produced by intestinal bacteria, and acts as a selective estrogen receptor modulator. Method: In this interventional study of clinical and biochemical characterization, urine isoflavone levels were measured in PCOS and control women before and three days after a defined isoflavone intervention via soy milk. In this interventional study, bacterial equol production was evaluated using the log(equol: daidzein ratio) and microbiome, metabolic, and predicted metagenome analyses were performed. Results: After isoflavone intervention, predicted stool metagenomic pathways, microbial alpha diversity, and glucose homeostasis in PCOS improved resembling the profile of the control group at baseline. In the whole cohort, larger equol production was associated with lower androgen as well as fertility markers. Conclusion: The dynamics in our metabolic, microbiome, and predicted metagenomic profiles underline the importance of external phytohormones on PCOS characteristics and a potential therapeutic approach or prebiotic in the future.

Intersection of Polycystic Ovary Syndrome and the Gut Microbiome

“…Using 16S rRNA gene sequencing, multiple studies reported that beta diversity was altered in fecal samples obtained from women with PCOS compared with healthy women [ 19 , 22 , 28 ]. However, in other studies, no significant difference in beta diversity was detected in women with PCOS compared with healthy women [ 21 , 26 , 33 , 34 ], potentially due to small sample sizes. Comparing adolescent girls with PCOS and obesity to BMI-matched controls, changes in beta diversity were also observed between the 2 groups [ 37 ].…”

“…Recent studies have shown that alpha diversity of gut microbiota is altered in women with PCOS compared with healthy women. By sampling the fecal microbial content and sequencing 16S ribosomal RNA (rRNA) genes amplified with universal bacterial primers, multiple studies demonstrated that alpha diversity of gut bacteria decreased in premenopausal women with PCOS as compared with age-matched, healthy women [ 19 , 22 , 26–28 , 33 ]. In contrast, 3 studies did not observe significant changes in alpha diversity between women with PCOS and healthy women, potentially due to small sample sizes [ 21 , 24 , 34 ].…”

“…Table 1 summarizes cohort characteristics of women included in studies of PCOS and the gut microbiome, while Table 2 summarizes the different taxa that were significantly altered in women with PCOS from the studies reviewed herein and is organized by bacterial phyla. Of the genera within phylum Bacteroidetes , Bacteroides were positively associated with PCOS in 5/7 studies and Parabacteroides were positively associated with PCOS in 2 studies [ 20 , 23–25 , 28 , 33 ], while the family S24-7 was negatively associated with PCOS in 2 studies [ 19 , 33 ]. Of the genera within phylum Firmicutes , family Clostridiaceae was positively associated with PCOS in 2 studies [ 22 , 25 ] and family Veillonellaceae in 2 other studies [ 27 , 33 ].…”

“…Of the genera within phylum Bacteroidetes , Bacteroides were positively associated with PCOS in 5/7 studies and Parabacteroides were positively associated with PCOS in 2 studies [ 20 , 23–25 , 28 , 33 ], while the family S24-7 was negatively associated with PCOS in 2 studies [ 19 , 33 ]. Of the genera within phylum Firmicutes , family Clostridiaceae was positively associated with PCOS in 2 studies [ 22 , 25 ] and family Veillonellaceae in 2 other studies [ 27 , 33 ]. Of the genera within phylum Proteobacteria , Escherichia , and Shigella were positively associated with PCOS in 2 studies [ 20 , 22 ].…”

Genistein: Dual Role in Women’s Health

“…For example, after isoflavone intervention, a 50 mg isoflavones/day regimen over just three consecutive days improved predicted stool metagenomic pathways, microbial alpha diversity, and glucose homeostasis in PCOS patients. The effect was so profound that, post-treatment, these variables resembled the profile of the control group at baseline [ 182 ]. Though further testing is required, evidence suggests that dietary supplementation of genistein may be a viable natural option for treating many of the symptoms of PCOS [ 175 , 176 , 177 , 178 , 179 ].…”