Abstract
Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.
Highlights
In Polycystic ovary syndrome (PCOS) groups, the levels of glycodeoxycholic acid (GDCA) and tauroursodeoxycholic acid (TUDCA) decreased due to the action of the encoded protein, bile salt hydrolases: an increased abundance of B.vulgatus reduced the concentrations of the bile acids, which negatively influenced the production of interleukin-Normally, IL-22 administration is very effective in ameliorating insulin resistance, regulating disrupted oestrous cycles, reversing ovary morphological changes and improving infertility, all typical aspect of PCOS phenotypes
In a meta-analysis of seven RCTs, Heshmati et al found no significant effect of probiotic supplementation on anthropometric indices like weight, body mass index (BMI), and waist circumferences as well as HOMA-Insulin resistance (IR) and LDL, in PCOS patients compared to placebo; they instead found a significant effect on glycemic control, with lower insulin levels, and on lipid metabolism, by lowering TG serum levels and increasing HDL
Qi et al reported low levels of IL-22 in individuals with PCOS, mediated by reduced IL-22 secretion induced by glycodeoxycholic acid; reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels were found after transplantation of fecal microbiota from women with PCOS to recipient mice, resulting in insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion, worst ovarian functions and infertility [31]
Summary
In 2003, the meeting of experts in Rotterdam revised the criterion; according to the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM) PCOS is defined by the presence of 2 out of the following 3 features: oligo- and/or anovulation, clinical and/or biochemical signs of hyperandrogenism, and/or polycystic ovarian morphology (PCOM). In the etiological hypotheses proposed over the years, the fact that, besides gynecological problems, PCOS can lead to systemic metabolic disorders (such as hyperinsulinemia and insulin resistance (IR), obesity, increased risk of type II diabetes, cardiovascular disease) has played a fundamental role [13]. The numerous evidence on the correlation between the intestinal microbiome and the development of metabolic disorders, have led to postulate the hypothesis that alterations in the microbiome are involved in the genesis of PCOS [14,15,16]. In consideration of the growing interest in the literature for the role of the microbiome in the genesis of numerous diseases, we try to summarize the main evidence published in literature regarding the relationship between microbiome and PCOS
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