The Gut Microbiome Is Altered in a Letrozole-Induced Mouse Model of Polycystic Ovary Syndrome

Study information

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study design

time series / longitudinal observational
laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

26731268

DOI Digital object identifier for electronic documents.

https://doi.org/10.1371/journal.pone.0146509

URI

https://pubmed.ncbi.nlm.nih.gov/26731268/

Authors

Kelley ST, Skarra DV, Rivera AJ, Thackray VG

Journal

PloS one

Year

2016

Women with polycystic ovary syndrome (PCOS) have reproductive and metabolic abnormalities that result in an increased risk of infertility, diabetes and cardiovascular disease. The large intestine contains a complex community of microorganisms (the gut microbiome) that is dysregulated in humans with obesity and type 2 diabetes. Using a letrozole-induced PCOS mouse model, we demonstrated significant diet-independent changes in the gut microbial community, suggesting that gut microbiome dysbiosis may also occur in PCOS women. Letrozole treatment was associated with a time-dependent shift in the gut microbiome and a substantial reduction in overall species and phylogenetic richness. Letrozole treatment also correlated with significant changes in the abundance of specific Bacteroidetes and Firmicutes previously implicated in other mouse models of metabolic disease in a time-dependent manner. Our results suggest that the hyperandrogenemia observed in PCOS may significantly alter the gut microbiome independently of diet.

Experiment 1

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Curated date: 2022/12/05

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Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled (if applicable): 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

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: polycystic ovary syndrome Cystic disease of ovaries,hyperandrogenemia,Multicystic ovaries,multicystic ovaries,Ovarian Degeneration, Sclerocystic,Ovarian Syndrome, Polycystic,Ovarian Syndromes, Polycystic,Ovaries, Sclerocystic,Ovary Syndrome, Polycystic,Ovary, Sclerocystic,PCO - Polycystic ovaries,Pco1,PCOD - Polycystic ovarian disease,PCOS,Pcos,PCOS - Polycystic ovarian syndrome,PCOS1,Polycystic ovarian disease,polycystic ovarian disease,Polycystic ovarian syndrome,Polycystic ovaries,polycystic ovaries,Polycystic ovaries (disorder),polycystic ovary,polycystic ovary syndrome,polycystic ovary syndrome 1,Sclerocystic Ovarian Degeneration,Sclerocystic Ovaries,Sclerocystic Ovary,Sclerocystic Ovary Syndrome,Stein Leventhal Syndrome,Stein-Leventhal synd.,Stein-Leventhal Syndrome,Stein-Leventhal syndrome,Syndrome, Polycystic Ovary,Syndrome, Stein-Leventhal

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Placebo-treated
Group 1 name Corresponds to the case (exposed) group for case-control studies: Letrozole-treated
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: At 4 weeks of age, the mice were implanted subcutaneously with a 3 mg letrozole pellet (Innovative Research of America, Sarasota, FL) that provided a constant, slow release of letrozole (50 μg/day) (n = 10/group).
Group 0 sample size Number of subjects in the control (unexposed) group: 10
Group 1 sample size Number of subjects in the case (exposed) group: 10
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): N/A

Lab analysis

Sequencing type: 16S

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

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Statistical test: Kruskall-Wallis

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)?: Yes

Alpha Diversity

Chao1 Abundance-based estimator of species richness: decreased

Signature 1

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Source:

Description:

Abundance in Group 1: decreased abundance in Letrozole-treated

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Muribaculaceae
Ruminococcus
Alistipes

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Source: S2 Fig

Description: Letrozole treatment results in significant changes in 48 bacterial OTUs as assessed by Kruskal-Wallis test.

The denovo OTU identifier, Test-Statistic, uncorrected p-value, corrected p-value using FDR and Bonferroni correction for multiple comparisons, placebo mean of ranked relative abundance over the entire study (weeks 0–5), letrozole mean from weeks 0–5, and the taxonomy of the closest match as identified using Greengenes are shown.

https://doi.org/10.1371/journal.pone.0146509.s002

Abundance in Group 1: increased abundance in Letrozole-treated

NCBI	Quality Control	Links
Allobaculum
Blautia

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