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Association between Polycystic Ovary Syndrome and Gut Microbiota.

Guo Y, Qi Y, Yang X, Zhao L, Wen S, Liu Y, Tang L - PLoS ONE (2016)

Bottom Line: Their ovarian morphologies normalized.The composition of gut microbiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella.These results indicated that dysbiosis of gut microbiota was associated with the pathogenesis of PCOS.

View Article: PubMed Central - PubMed

Affiliation: Department of Microecology, School of Basic Medical Science, Dalian Medical University, Dalian, Liaoning, China.

ABSTRACT
Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. It is difficult to treat PCOS because of its complex etiology and pathogenesis. Here, we characterized the roles of gut microbiota on the pathogenesis and treatments in letrozole (a nonsteroidal aromatase inhibitor) induced PCOS rat model. Changes in estrous cycles, hormonal levels, ovarian morphology and gut microbiota by PCR-DGGE and real-time PCR were determined. The results showed that PCOS rats displayed abnormal estrous cycles with increasing androgen biosynthesis and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Meanwhile, the composition of gut microbiota in letrozole-treated rats was different from that in the controls. Lactobacillus, Ruminococcus and Clostridium were lower while Prevotella was higher in PCOS rats when compared with control rats. After treating PCOS rats with Lactobacillus and fecal microbiota transplantation (FMT) from healthy rats, it was found that the estrous cycles were improved in all 8 rats in FMT group, and in 6 of the 8 rats in Lactobacillus transplantation group with decreasing androgen biosynthesis. Their ovarian morphologies normalized. The composition of gut microbiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella. These results indicated that dysbiosis of gut microbiota was associated with the pathogenesis of PCOS. Microbiota interventions through FMT and Lactobacillus transplantation were beneficial for the treatments of PCOS rats.

No MeSH data available.


Related in: MedlinePlus

Time lines of the animal experiments.To establish the PCOS rat model, SD rats were treated with letrozole at a concentration of 1 mg/kg once daily for 21 days. After that, PCOS FMT group was treated with 2×109 fecal microbiota once daily, PCOS Lactobacillus transplantation group was treated with 2×109Lactobacillus once daily, PCOS group and control group were treated with normal saline for 14 days. On day 21, all rat fecal samples were collected. On day 36, all rat blood samples, ovarian tissue samples and fecal samples were collected.
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pone.0153196.g001: Time lines of the animal experiments.To establish the PCOS rat model, SD rats were treated with letrozole at a concentration of 1 mg/kg once daily for 21 days. After that, PCOS FMT group was treated with 2×109 fecal microbiota once daily, PCOS Lactobacillus transplantation group was treated with 2×109Lactobacillus once daily, PCOS group and control group were treated with normal saline for 14 days. On day 21, all rat fecal samples were collected. On day 36, all rat blood samples, ovarian tissue samples and fecal samples were collected.

Mentions: Six-week-old specific-pathogen free (SPF) level inbred female Sprague-Dawley (SD) rats (mean body weight, 180 g) were purchased from Animal Facility of Dalian Medical University. All animal experiments were approved by the Animal Care Committee of Dalian Medical University, China (SCXK-2013-0003). All animals were feed with commercial diet (51% nitrogen-free extract, 24.9% crude protein, 4.6% crud fat, 6.6% crud ash, 4.1% crud fiber and 8.9% moisture), and tap water ad libitum. In this experiment, 32 female SD rats were randomly assigned into 4 groups of 8 rats each, including a control group that received a gavage of normal saline, and three treatment groups (PCOS, PCOS FMT and PCOS Lactobacillus transplantation groups) administered a gavage of letrozole (Novartis Pharma Schweiz AG, Switzerland) at a concentration of 1 mg/kg once daily for 21 consecutive days. The establishment of PCOS rat model was similar to that of Kalafi. et al [26]. On day 21, all rat fecal samples were collected. Control rat fecal samples and PCOS rat fecal samples were used for DGGE analysis to evaluate the gut microbiota shift in PCOS rats. In order to quantify the differences of microbita for all rats on day 21, real-time PCR analysis was applied. Twenty four hours after the last dose of letrozole (on day 22), PCOS FMT rats were administered a gavage of fecal supernatant with 2×109 fecal microbiota, PCOS Lactobacillus transplantation rats were administered a gavage of 2×109Lactobacillus, the control rats and PCOS rats were administered a gavage of normal saline for 14 consecutive days. On day 36, all rat fecal samples were collected for real-time PCR analysis. Then all rats were sacrificed by decapitation. Trunk blood samples and ovarian tissue samples were obtained for the subsequent experiments. The treatments of the animals and sample collections were showed in Fig 1.


Association between Polycystic Ovary Syndrome and Gut Microbiota.

Guo Y, Qi Y, Yang X, Zhao L, Wen S, Liu Y, Tang L - PLoS ONE (2016)

Time lines of the animal experiments.To establish the PCOS rat model, SD rats were treated with letrozole at a concentration of 1 mg/kg once daily for 21 days. After that, PCOS FMT group was treated with 2×109 fecal microbiota once daily, PCOS Lactobacillus transplantation group was treated with 2×109Lactobacillus once daily, PCOS group and control group were treated with normal saline for 14 days. On day 21, all rat fecal samples were collected. On day 36, all rat blood samples, ovarian tissue samples and fecal samples were collected.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836746&req=5

pone.0153196.g001: Time lines of the animal experiments.To establish the PCOS rat model, SD rats were treated with letrozole at a concentration of 1 mg/kg once daily for 21 days. After that, PCOS FMT group was treated with 2×109 fecal microbiota once daily, PCOS Lactobacillus transplantation group was treated with 2×109Lactobacillus once daily, PCOS group and control group were treated with normal saline for 14 days. On day 21, all rat fecal samples were collected. On day 36, all rat blood samples, ovarian tissue samples and fecal samples were collected.
Mentions: Six-week-old specific-pathogen free (SPF) level inbred female Sprague-Dawley (SD) rats (mean body weight, 180 g) were purchased from Animal Facility of Dalian Medical University. All animal experiments were approved by the Animal Care Committee of Dalian Medical University, China (SCXK-2013-0003). All animals were feed with commercial diet (51% nitrogen-free extract, 24.9% crude protein, 4.6% crud fat, 6.6% crud ash, 4.1% crud fiber and 8.9% moisture), and tap water ad libitum. In this experiment, 32 female SD rats were randomly assigned into 4 groups of 8 rats each, including a control group that received a gavage of normal saline, and three treatment groups (PCOS, PCOS FMT and PCOS Lactobacillus transplantation groups) administered a gavage of letrozole (Novartis Pharma Schweiz AG, Switzerland) at a concentration of 1 mg/kg once daily for 21 consecutive days. The establishment of PCOS rat model was similar to that of Kalafi. et al [26]. On day 21, all rat fecal samples were collected. Control rat fecal samples and PCOS rat fecal samples were used for DGGE analysis to evaluate the gut microbiota shift in PCOS rats. In order to quantify the differences of microbita for all rats on day 21, real-time PCR analysis was applied. Twenty four hours after the last dose of letrozole (on day 22), PCOS FMT rats were administered a gavage of fecal supernatant with 2×109 fecal microbiota, PCOS Lactobacillus transplantation rats were administered a gavage of 2×109Lactobacillus, the control rats and PCOS rats were administered a gavage of normal saline for 14 consecutive days. On day 36, all rat fecal samples were collected for real-time PCR analysis. Then all rats were sacrificed by decapitation. Trunk blood samples and ovarian tissue samples were obtained for the subsequent experiments. The treatments of the animals and sample collections were showed in Fig 1.

Bottom Line: Their ovarian morphologies normalized.The composition of gut microbiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella.These results indicated that dysbiosis of gut microbiota was associated with the pathogenesis of PCOS.

View Article: PubMed Central - PubMed

Affiliation: Department of Microecology, School of Basic Medical Science, Dalian Medical University, Dalian, Liaoning, China.

ABSTRACT
Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. It is difficult to treat PCOS because of its complex etiology and pathogenesis. Here, we characterized the roles of gut microbiota on the pathogenesis and treatments in letrozole (a nonsteroidal aromatase inhibitor) induced PCOS rat model. Changes in estrous cycles, hormonal levels, ovarian morphology and gut microbiota by PCR-DGGE and real-time PCR were determined. The results showed that PCOS rats displayed abnormal estrous cycles with increasing androgen biosynthesis and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Meanwhile, the composition of gut microbiota in letrozole-treated rats was different from that in the controls. Lactobacillus, Ruminococcus and Clostridium were lower while Prevotella was higher in PCOS rats when compared with control rats. After treating PCOS rats with Lactobacillus and fecal microbiota transplantation (FMT) from healthy rats, it was found that the estrous cycles were improved in all 8 rats in FMT group, and in 6 of the 8 rats in Lactobacillus transplantation group with decreasing androgen biosynthesis. Their ovarian morphologies normalized. The composition of gut microbiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella. These results indicated that dysbiosis of gut microbiota was associated with the pathogenesis of PCOS. Microbiota interventions through FMT and Lactobacillus transplantation were beneficial for the treatments of PCOS rats.

No MeSH data available.


Related in: MedlinePlus