Intersection of Polycystic Ovary Syndrome and the Gut Microbiome

Maryan G. Rizk; Varykina G. Thackray

Disclosures

J Endo Soc. 2021;5(2) 

In This Article

Abstract and Introduction

Abstract

The etiology of polycystic ovary syndrome (PCOS) remains unclear, although studies indicate that both genetic and environmental factors contribute to the syndrome. In 2012, Tremellen and Pearce proposed the idea that dysbiosis of the intestinal (gut) microbiome is a causative factor of metabolic and reproductive manifestations of PCOS. In the past 5 years, studies in both humans and rodent models have demonstrated that changes in the taxonomic composition of gut bacteria are associated with PCOS. Studies have also clearly shown that these changes in gut microbiota are associated with PCOS as opposed to obesity, since these changes are observed in women with PCOS that are both of a normal weight or obese, as well as in adolescent girls with PCOS and obesity compared with body mass index- and age-matched females without the disorder. Additionally, studies in both women with PCOS and rodent models of PCOS demonstrated that hyperandrogenism is associated with gut microbial dysbiosis, indicating that androgens may modulate the gut microbial community in females. One study reported that the fecal microbiome transplantation of stool from women with PCOS or exposure to certain bacteria resulted in a PCOS-like phenotype in mice, while other studies showed that exposure to a healthy gut microbiome, pre/probiotics, or specific gut metabolites resulted in protection from developing PCOS-like traits in mice. Altogether, these results suggest that dysbiosis of the gut microbiome may be sufficient to develop PCOS-like symptoms and that modulation of the gut microbiome may be a potential therapeutic target for PCOS.

Introduction

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting 5% to 10% of women of reproductive age worldwide.[1,2] Diagnosis of PCOS includes 2/3 clinical presentations: (1) clinical or biochemical hyperandrogenism (HA), (2) oligomenorrhea or anovulation, and (3) polycystic ovaries.[3] Women with PCOS are at a higher risk for infertility and pregnancy complications.[4–7] In PCOS, metabolic dysregulation is correlated with HA, occurs independently of body mass index (BMI), and includes obesity, insulin resistance (IR), and dyslipidemia (Figure 1),[8–10] which leads to an increased risk of developing type 2 diabetes (T2D), hypertension, and nonalcoholic fatty liver disease.[6,11–14] Due to its prevalence and association with multiple chronic diseases, studying the mechanisms driving the etiology and pathogenesis of PCOS is of utmost importance in facilitating the development of novel therapies for PCOS.

Figure 1.

Correlations between hyperandrogenism (HA), dysbiosis of the gut microbiome, and metabolic dysfunction. A: Link between HA and dysbiosis of the gut microbiome. Recent studies in women and rodent models demonstrated that HA is correlated with dysbiosis of the gut microbiome, including changes in the overall biodiversity of gut bacteria as well as the relative abundance of certain bacteria. In addition, 1 study reported that introducing stool from women with PCOS or a bacterial species (B. vulgatus) in antibiotic-treated mice resulted in HA, suggesting that gut microbial dysbiosis or the overabundance of specific bacteria may be sufficient to induce PCOS-like symptoms. B: Link between HA and metabolic dysfunction. Metabolic dysfunction, including weight gain, insulin resistance (IR), and dyslipidemia, occurs predominantly in women with PCOS diagnosed with HA and ovulatory dysfunction, independent of body mass index. C: Link between dysbiosis of the gut microbiome and metabolic dysfunction. Gut dysbiosis has been associated with obesity, IR, and impaired lipid metabolism in metabolic diseases, including metabolic syndrome, type 2 diabetes, nonalcoholic fatty liver disease, and PCOS. Despite the tripartite set of correlations between HA, gut microbial dysbiosis, and metabolic dysfunction, the mechanisms of how each player affects the other 2 are still largely unknown. Future studies will be required to decipher how the gut microbiome communicates with the host and vice versa in order to alter or respond to varying levels of steroid and metabolic hormones.

The intestinal (gut) microbiome is comprised of a community of diverse bacteria, archaea, fungi, protozoa, and viruses, along with their metabolites. This community plays an important role in host physiology, including immunity, the health of the gut epithelial barrier, production of vitamin B12, and production of short-chain fatty acids (SCFAs) via fermentation of fiber, metabolism, and neurological functions.[15] Alterations in gut microbiota have been associated with metabolic diseases (Figure 1), autoimmune diseases, neurological disorders, and cardiovascular disease.[16] In 2012, Tremellen and Pearce proposed that a connection might exist between dysbiosis of the gut microbiome and the metabolic and reproductive manifestations of PCOS.[17] Two studies in 2016 and 2017 first reported evidence that changes in the gut microbiome were associated with PCOS in a mouse model of PCOS and in women with the disorder.[18,19] Since then, multiple subsequent studies in humans[20–28] and rodents[29–32] provided further evidence that dysbiosis of the gut microbiome is associated with PCOS.

In this review, we highlight recent findings on the association between the gut microbiome and PCOS, the relationship between HA and the gut microbiome in PCOS, the relationship between substrates and metabolites of the gut microbiota and PCOS, and potential gut microbiota-altering treatments as therapies of PCOS. To do so, we used the following search terms in NCBI PubMed: "microbiome," "microbiota," and "polycystic ovary syndrome." We confined our search criteria to primary research articles of human and rodent studies on PCOS and the gut microbiome between 2016 and 2020.

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