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

From BugSigDB
Reviewed Marked as Reviewed by KateRasheed on 2025-8-4
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


Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

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
ANOVA
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.01
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

Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/06/06

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 5D

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


Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/06/05

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

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,Polycystic ovary syndrome
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

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

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

Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/06/06

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 5D

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


Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/06/05

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp, Ese

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
DHT-induced PCOS rats treated with Berberine daily, starting 7 weeks after DHT implantation

Lab analysis

Statistical Analysis

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.01

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
increased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/06/06

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 5D

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

Experiment 4


Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/06/06

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to diet Response to diet,response to diet
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

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)?
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

Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

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
Bacteroides
Ruminococcaceae bacterium UCG-005
Ruminococcus_1Ruminococcus_1

Revision editor(s): Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/07/08

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: decreased abundance in HFD (High fat diet)

NCBI Quality ControlLinks
Prevotellaceae_Ga6A1_groupPrevotellaceae_Ga6A1_group
Prevotella_9Prevotella_9
Treponema_2Treponema_2

Revision editor(s): Anne-mariesharp

Experiment 5


Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/06/06

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

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,Polycystic ovary syndrome
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

Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

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
Bacteroides
Prevotella_9Prevotella_9

Revision editor(s): Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/07/08

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Supplementary figure 2B

Description: Different fecal microbiota in rats at the genus level

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

NCBI Quality ControlLinks
Prevotellaceae_Ga6A1_groupPrevotellaceae_Ga6A1_group

Revision editor(s): Anne-mariesharp

Experiment 6


Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/06/13

Curator: Amaanarif

Revision editor(s): Amaanarif, Anne-mariesharp, Ese

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
DHT (Dihydrotestosterone) + Diane-35
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
DHT-induced PCOS rats treated with Diane-35 daily, starting 7 weeks after DHT implantation

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

Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/06/13

Curator: Amaanarif

Revision editor(s): Amaanarif, Anne-mariesharp

Source: Supplementary Figure 2C

Description: Different fecal microbiota in rats at the genus level

Abundance in Group 1: increased abundance in DHT (Dihydrotestosterone) + Diane-35

NCBI Quality ControlLinks
Ruminococcaceae_UCG-013Ruminococcaceae_UCG-013

Revision editor(s): Amaanarif, Anne-mariesharp

Experiment 7


Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/06/13

Curator: Amaanarif

Revision editor(s): Amaanarif, Anne-mariesharp, Ese

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
DHT (Dihydrotestosterone) + Probiotics
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
DHT-induced PCOS rats treated with Probiotics daily, starting 7 weeks after DHT implantation

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

Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/06/13

Curator: Amaanarif

Revision editor(s): Amaanarif, Anne-mariesharp

Source: Supplementary Figure 2D

Description: Different fecal microbiota in rats at the genus level

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

NCBI Quality ControlLinks
Prevotellaceae_Ga6A1_groupPrevotellaceae_Ga6A1_group

Revision editor(s): Amaanarif, Anne-mariesharp

Experiment 8


Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/07/08

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp, Ese

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
DHT-induced PCOS rats treated with Berberine daily, starting 7 weeks after DHT 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
increased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/07/08

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 6E, Supplementary Figure 2E

Description: Different fecal microbiota in rats at the genus level

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

NCBI Quality ControlLinks
Blautia
Phascolarctobacterium
Thomasclavelia
Prevotellaceae_NK3B31_groupPrevotellaceae_NK3B31_group

Revision editor(s): Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-8-4

Curated date: 2025/07/08

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 6E, Supplementary Figure 2E

Description: Different fecal microbiota in rats at the genus level

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

NCBI Quality ControlLinks
Eubacterium coprostanoligenes
Lachnospiraceae bacterium NK4A136
Ruminococcaceae bacterium UCG-005
unclassified Oscillospiraceae
Ruminococcus_1Ruminococcus_1
Ruminiclostridium_9Ruminiclostridium_9
Lachnospiraceae_UCG-005Lachnospiraceae_UCG-005
Ruminococcaceae_UCG-014Ruminococcaceae_UCG-014
Treponema_2Treponema_2

Revision editor(s): Anne-mariesharp