Role of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome: a review

Abstract

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder. Typically, it is characterized by hirsutism, hyperandrogenism, ovulatory dysfunction, menstrual disorders and infertility. To date, its pathogenesis remains unclear. However, insulin resistance (IR) is considered as the primary pathological basis for its reproductive dysfunction. On the other hand, a condition in which insulin is over-secreted is called hyperinsulinemia. IR/Hyperinsulinemia is associated with chronic inflammation, hormonal changes, follicular dysplasia, endometrial receptivity changes, and abortion or infertility. Additionally, it increases incidence of complications during pregnancy and has been associated with anxiety, depression, and other psychological disorders. Gut microbiota, the "second genome" acquired by the human body, can promote metabolism, immune response through interaction with the external environment. Gut microbiota dysbiosis can cause IR, which is closely linked to the occurrence of PCOS. This article reviewed recent findings on the roles of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome.

Keywords: Gut microbiota; Hyperandrogenism; Insulin resistance; PCOS.

Fig. 1

Crosstalk between the gut microbiota and the mammalian host in inflammation and metabolism. The gut microbiota can contribute to host insulin resistance, low-grade inflammation, and hyperandrogenism(HA) through a range of molecular interactions with the host and therefore can indirectly participate in the onset of PCOS

Fig. 2

①Gut microbiota can cause IR by affecting lipopolysaccharide (LPS) and its receptor CD14(LPS-CD14; ②SCFAs protect intestinal barrier integrity and act on beta cells to promote insulin secretion, thus improving metabolism; ③Bile acids (BAs) are signaling molecules that regulate glucose metabolism and promote insulin sensitivity; ④The metabolic disorder of amino acids might aggravate IR by changing glucose metabolism or inducing inflammation;⑤A vicious cycle between hyperandrogenemia and IR in PCOS, thus promoting the occurrence and development of PCOS; ⑥Gut microbiota and its metabolites cause insulin resistance and hyperinsulinemia by stimulating the secretion of gut-brain peptides and regulating inflammation pathway activation. LPS: lipopolysaccharide; SCFA: short-chain fatty acid; BCAA: branch-chain amino acid; BA: Bile acids