Diversity of the Gut Microbiota in Dihydrotestosterone-Induced PCOS Rats and the Pharmacologic Effects of Diane-35, Probiotics, and Berberine

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Zhang F, Ma T, Cui P, Tamadon A, He S, Huo C, Yierfulati G, Xu X, Hu W, Li X, Shao LR, Guo H, Feng Y, Xu C
Journal
Frontiers in microbiology
Year
2019
Keywords:
DHT, Diane-35, PCOS, berberine, gut microbiota, probiotics
Polycystic ovary syndrome (PCOS) is a frequent endocrine and metabolic syndrome in reproductive-age women. Recently, emerging evidence has shown that gut microbiota is closely related to metabolic diseases such as type 2 diabetes, obesity and PCOS. In the present study, we established dihydrotestosterone (DHT)-induced PCOS rats and used Illumina MiSeq sequencing (PE300) to examine the composition, diversity, and abundance of the gut microbiota in PCOS. We compared the effects of three PCOS treatments: Diane-35 (estrogen and progesterone), probiotics and berberine. The DHT-induced rats showed constant estrous cycles, the loss of mature ovarian follicles, insulin resistance and obesity. The reproductive and metabolic functions in the PCOS rats were improved by treatment with Diane-35 and probiotics. Diane-35 and probiotics could restore the diversity of the gut microbiota, and the recovery of gut microbiota disorders improved the reproductive function in PCOS-like rats. However, berberine drastically reduced the species diversity and amount of gut microbiota and showed no improvement in PCOS. The findings of this study will help us to better understand the influence of the gut microbiota in the metabolic and reproductive alterations in PCOS as well as suggest opportunities for future personal dietary guidance for PCOS.

Experiment 1


Needs review

Curated date: 2025/06/05

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Rattus norvegicus
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
Response to diet Response to diet,response to diet
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
HFD (High fat diet)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Female Wistar rats of 21 days fed a high-fat chow, energy%: 60% from fat, 20% from carbohydrates and 20% from protein, 5.24 kcal/g (Research Diets, D12492).
Group 0 sample size Number of subjects in the control (unexposed) group
6
Group 1 sample size Number of subjects in the case (exposed) group
6

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
T-Test
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

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
decreased

Signature 1

Needs review

Curated date: 2025/06/06

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 5

Description: The abundance of Spirochaetaceae at the family level.

Abundance in Group 1: decreased abundance in HFD (High fat diet)

NCBI Quality ControlLinks
Spirochaetaceae

Revision editor(s): Anne-mariesharp

Experiment 2


Needs review

Curated date: 2025/06/05

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
DHT (Dihydrotestosterone)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Female Wistar rats of 21 days fed with standard chow, energy%: 10.3% from fat, 65.5% from carbohydrate and 24.2% from protein, 3.52kcal/g (Shanghai SLAC Laboratory Animal) and implanted subcutaneously with slow-release Dihydrotestosterone (15 mg, 75-day release) silicone tubes at 21 days old to induce Polycystic ovary syndrome

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2025/06/06

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 5

Description: The abundance of Spirochaetaceae at the family level.

Abundance in Group 1: decreased abundance in DHT (Dihydrotestosterone)

NCBI Quality ControlLinks
Spirochaetaceae

Revision editor(s): Anne-mariesharp

Experiment 3


Needs review

Curated date: 2025/06/05

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
DHT (Dihydrotestosterone) + Berberine
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Dihydrotestosterone-implanted rats fed standard chow and treated daily by oral gavage with berberine hydrochloride (dissolved in 1% CMC at 150 mg/kg body weight) starting 7 weeks post-implantation.

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased
Richness Number of species
decreased

Signature 1

Needs review

Curated date: 2025/06/06

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 5

Description: The abundance of Spirochaetaceae at the family level.

Abundance in Group 1: decreased abundance in DHT (Dihydrotestosterone) + Berberine

NCBI Quality ControlLinks
Spirochaetaceae

Revision editor(s): Anne-mariesharp

Signature 2

Needs review

Curated date: 2025/06/13

Curator: Amaanarif

Revision editor(s): Amaanarif

Source: Figure 6

Description: Decreased in the DHT + Berberine group compared to control group.

Abundance in Group 1: decreased abundance in DHT (Dihydrotestosterone) + Berberine

NCBI Quality ControlLinks
Lachnospiraceae
unclassified Oscillospiraceae
Desulfovibrio
unclassified Lachnospiraceae
Alloprevotella
Oscillibacter

Revision editor(s): Amaanarif

Experiment 4


Needs review

Curated date: 2025/06/06

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
HFD (High fat diet)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Female Wistar rats of 21 days fed a high-fat chow, energy%: 60% from fat, 20% from carbohydrates and 20% from protein, 5.24 kcal/g (Research Diets, D12492).

Lab analysis

Statistical Analysis

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
decreased

Signature 1

Needs review

Curated date: 2025/06/06

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 6A, Supplementary figure 2A

Description: Different fecal microbiota in rats at the genus level

Abundance in Group 1: increased abundance in HFD (High fat diet)

NCBI Quality ControlLinks
Ruminococcus
Ruminococcaceae bacterium UCG-005
Prevotella
Treponema
Bacteroides
Prevotellaceae_Ga6A1_groupPrevotellaceae_Ga6A1_group

Revision editor(s): Anne-mariesharp

Experiment 5


Needs review

Curated date: 2025/06/06

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
DHT (Dihydrotestosterone)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Female Wistar rats of 21 days fed with standard chow, energy%: 10.3% from fat, 65.5% from carbohydrate and 24.2% from protein, 3.52kcal/g (Shanghai SLAC Laboratory Animal) and implanted subcutaneously with slow-release Dihydrotestosterone (15 mg, 75-day release) silicone tubes at 21 days old to induce Polycystic ovary syndrome

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2025/06/06

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 6B, Supplementary figure 2B

Description: Different fecal microbiota in rats at the genus level

Abundance in Group 1: increased abundance in DHT (Dihydrotestosterone)

NCBI Quality ControlLinks
Prevotella
Bacteroides
Prevotellaceae_Ga6A1_groupPrevotellaceae_Ga6A1_group

Revision editor(s): Anne-mariesharp

Experiment 6


Needs review

Curated date: 2025/06/13

Curator: Amaanarif

Revision editor(s): Amaanarif

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
DHT + Diane-35
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Female Wistar rats of 21 days treated with DHT and Diane-35; diet conditions same as control.

Lab analysis

Statistical Analysis

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

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
decreased

Signature 1

Needs review

Curated date: 2025/06/13

Curator: Amaanarif

Revision editor(s): Amaanarif

Source: Supplemental Figure 2

Description: Decreased abundance of Ruminococcaceae_UCG-013 in DHT + Diane-35 treated rats compared to control.

Abundance in Group 1: decreased abundance in DHT + Diane-35

NCBI Quality ControlLinks
Oscillospiraceae

Revision editor(s): Amaanarif

Experiment 7


Needs review

Curated date: 2025/06/13

Curator: Amaanarif

Revision editor(s): Amaanarif

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Female rats treated with DHT and Diane-35; compared to untreated control group

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
decreased

Signature 1

Needs review

Curated date: 2025/06/13

Curator: Amaanarif

Revision editor(s): Amaanarif

Source: Supplemental Figure 2

Description: Decreased abundance of Christensenellaceae_R-7_group in DHT + Diane-35-treated rats

Abundance in Group 1: decreased abundance in DHT + Diane-35

NCBI Quality ControlLinks
Christensenellaceae
Lactobacillus

Revision editor(s): Amaanarif