Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice

Study information

Reviewed Marked as Reviewed by KateRasheed on 2025-6-6

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

37443082

DOI Digital object identifier for electronic documents.

10.1186/s13048-023-01227-w

URI Uniform resource identifier for web resources.

Authors

Zhang H, Zheng L, Li C, Jing J, Li Z, Sun S, Xue T, Zhang K, Xue M, Cao C, Ouyang L, Qian Z, Xu R, He Z, Ma R, Chen L, Yao B

Journal

Journal of ovarian research

Year

2023

Keywords:

Gut microbiota, Inflammation, Omega-3 PUFAs, Polycystic ovary syndrome

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.

Experiment 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-6-6

Curated date: 2025/04/25

Curator: MyleeeA

Revision editor(s): MyleeeA, Svetlana up

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: Mus musculus

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Treatment outcome measurement Treatment outcome measurement,treatment outcome measurement

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Control group

Group 1 name Corresponds to the case (exposed) group for case-control studies: Polycystic ovary syndrome (PCOS)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Polycystic ovary syndrome (PCOS) mice were treated with an equal volume of corn oil at 2 g/kg

Group 0 sample size Number of subjects in the control (unexposed) group: 3

Group 1 sample size Number of subjects in the case (exposed) group: 3

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: ANOVA

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

Alpha Diversity

Chao1 Abundance-based estimator of species richness: unchanged

Richness Number of species: decreased

Signature 1

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Source: Figure 4G

Description: Differential microbial abundance between Polycystic ovary syndrome (PCOS) and Control

Abundance in Group 1: increased abundance in Polycystic ovary syndrome (PCOS)

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Alloprevotella

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Source: Figure 4I

Description: Differential microbial abundance between Polycystic ovary syndrome (PCOS) and Control

Abundance in Group 1: decreased abundance in Polycystic ovary syndrome (PCOS)

NCBI	Quality Control	Links
Alistipes

Revision editor(s): MyleeeA

Experiment 2

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Curated date: 2025/04/25

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Polycystic ovary syndrome (PCOS) mice

Group 1 name Corresponds to the case (exposed) group for case-control studies: Omega-3 mice

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Omega-3-treated mice, after 3 weeks of DHEA treatment, the mice received another 8 weeks of treatment by gavage with omega-3 PUFAs (2 g/kg every 2 days)