Evaluation on the characteristics of gut microbiome in polycystic ovary syndrome rats induced by dihydrotestosterone or letrozole

Abstract

Background: Etiology of polycystic ovary syndrome (PCOS) is unclear. Recent reports indicated that gut microbiota regulates metabolism and plays a major role in the development of PCOS. The present study aimed to investigate and compare the effects of dihydrotestosterone or letrozole on the gut microbiome in rats.Methods: We used dihydrotestosterone (DHT) or letrozole (LET) to induce PCOS model rats. At the end of the experiment, ovarian morphology, hormonal and metabolic status were investigated in all rats. We analyzed the gut microbiome of rats by deep sequencing the 16S rDNA V3-V4 hypervariable regions. Predictive metagenomics profiling using PICRUST revealed functional alternation of the KEGG pathways in rats.Result: Rats induced by letrozole exhibited endocrine and reproductive characteristics, such as hyperandrogenism, abnormal oestrus cycles or complete acyclic, polycystic ovaries, and obesity. DHT-induced rats were obesity, irregular oestrus cycles, polycystic ovaries, with lower level of HDL-C and lower activity of SOD than controls. The bacterial diversity (Chao1 and Ace) of DHT group was decreased compared with the control group. Furthermore, principal coordinates analysis revealed that DHT and control groups could be distinguished from each other. The DHT group exhibited increased numbers of Firmicutes, Cyanobacteria, Actinobacteria and Saccharibacteria, and decreased Bacteroidetes compared with the control group at the phylum level. Moreover, PICRUST-predicted KEGG pathways related to Carbohydrate metabolism, Amino acid metabolism, Metabolism of terpenoids and polyketides, Metabolism of other amino acids, Replication and repair, Lipid metabolism and Energy metabolism, Translation, Folding, sorting and degradation and Xenobiotics biodegradation and metabolism were significantly elevated in the DHT group. And pathways related to Metabolism of terpenoids and polyketides, Replication and repair, Xenobiotics biodegradation and metabolism, Nucleotide metabolism, Infectious diseases and Excretory system were significantly elevated in the LET group.Conclusion: The findings of the present study indicated that DHT affected the composition and diversity of gut microbial community, and leads to the gut dysbiosis. KEGG function profiles calculated by PICRUST suggested that DHT may affect metabolism of the gut microbiota more directly than letrozle.

Interplay between PCOS and microbiome: The road less travelled

“…19 These changes in the levels of sex- Further studies on rat model have reported increased weight gain on induction of DHT/letrozole in rats after few weeks. 22,23 This was in accordance with a human study on normal weight women where HA caused increased abdominal fat storage and subsequently IR. 24,25 In fact, a recent study found that dysbiosis of the gut microbiota caused by androgens may exacerbate metabolic as well as endocrine function in PCOS 19 and exposure to a healthy gut flora protected a PCOS mouse model from developing metabolic abnormalities.…”

“…Infusion of microbes from healthy individual into the PCOS rats showed improved estrous cycle, decreased androgen production, and normalized ovarian morphology implying a link between HA and microbiota composition in PCOS 20,21 . Further studies on rat model have reported increased weight gain on induction of DHT/letrozole in rats after few weeks 22,23 . This was in accordance with a human study on normal weight women where HA caused increased abdominal fat storage and subsequently IR 24,25 .…”