Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice
Abstract Background Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatt...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-023-01227-w |
| _version_ | 1797778777608028160 |
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| author | Hong Zhang Lu Zheng Chuwei Li Jun Jing Zhou Li Shanshan Sun Tongmin Xue Kemei Zhang Mengqi Xue Chun Cao Lei Ouyang Zhang Qian Rui Xu Zhaowanyue He Rujun Ma Li Chen Bing Yao |
| author_facet | Hong Zhang Lu Zheng Chuwei Li Jun Jing Zhou Li Shanshan Sun Tongmin Xue Kemei Zhang Mengqi Xue Chun Cao Lei Ouyang Zhang Qian Rui Xu Zhaowanyue He Rujun Ma Li Chen Bing Yao |
| author_sort | Hong Zhang |
| collection | DOAJ |
| description | Abstract Background Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. Methods We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. Results We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1β, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. Conclusion These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance. |
| first_indexed | 2024-03-12T23:21:30Z |
| format | Article |
| id | doaj.art-9735ad415dba4bcd9b3088b61f7adbf3 |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-03-12T23:21:30Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-9735ad415dba4bcd9b3088b61f7adbf32023-07-16T11:24:47ZengBMCJournal of Ovarian Research1757-22152023-07-0116111710.1186/s13048-023-01227-wEffects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome miceHong Zhang0Lu Zheng1Chuwei Li2Jun Jing3Zhou Li4Shanshan Sun5Tongmin Xue6Kemei Zhang7Mengqi Xue8Chun Cao9Lei Ouyang10Zhang Qian11Rui Xu12Zhaowanyue He13Rujun Ma14Li Chen15Bing Yao16Center of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityCenter of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityCenter of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityCenter of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityCenter of Reproductive Medicine, Nanjing Jinling Hospital, School of Medicine, Jiangsu UniversityJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal UniversityReproductive Medical Center, Clinical Medical College (Northern Jiangsu People’s Hospital), Yangzhou UniversityReproductive Medical Center, Jinling Hospital Department, Nanjing Medical UniversityReproductive Medical Center, Jinling Hospital Department, Nanjing Medical UniversityDepartment of Reproductive Medicine, Affiliated Jinling Hospital, The First School of Clinical Medicine, Southern Medical UniversityDepartment of Reproductive Medicine, Affiliated Jinling Hospital, The First School of Clinical Medicine, Southern Medical UniversityCenter of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityCenter of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityCenter of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityCenter of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityCenter of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityCenter of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityAbstract Background Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. Methods We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. Results We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1β, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. Conclusion These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.https://doi.org/10.1186/s13048-023-01227-wOmega-3 PUFAsPolycystic ovary syndromeInflammationGut microbiota |
| spellingShingle | Hong Zhang Lu Zheng Chuwei Li Jun Jing Zhou Li Shanshan Sun Tongmin Xue Kemei Zhang Mengqi Xue Chun Cao Lei Ouyang Zhang Qian Rui Xu Zhaowanyue He Rujun Ma Li Chen Bing Yao Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice Journal of Ovarian Research Omega-3 PUFAs Polycystic ovary syndrome Inflammation Gut microbiota |
| title | Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice |
| title_full | Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice |
| title_fullStr | Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice |
| title_full_unstemmed | Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice |
| title_short | Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice |
| title_sort | effects of gut microbiota on omega 3 mediated ovary and metabolic benefits in polycystic ovary syndrome mice |
| topic | Omega-3 PUFAs Polycystic ovary syndrome Inflammation Gut microbiota |
| url | https://doi.org/10.1186/s13048-023-01227-w |
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