Effects of Glucagon-Like Peptide-1 Receptor Agonists on Gut Microbiota in Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome Mice: Compared Evaluation of Liraglutide and Semaglutide Intervention

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Reviewed Marked as Reviewed by Svetlana up on 2025-1-30
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Xiong C, Wu J, Ma Y, Li N, Wang X, Li Y, Ding X
Journal
Diabetes, metabolic syndrome and obesity : targets and therapy
Year
2024
Keywords:
GLP-1 receptor agonists, PCOS, gut microbiota, metabolism
PURPOSE: Polycystic ovary syndrome (PCOS) is a frequent cause of infertility in reproductive-age women. Our work aims to evaluate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on gut microbiota, with metabolic parameters including body weight and the hormone profile in PCOS. PATIENTS AND METHODS: Dehydroepiandrosterone (DHEA)-induced PCOS mice were established and then treated with two GLP-1RAs: liraglutide and novel form semaglutide for four weeks. Changes in body weight and metabolic parameters were measured. Fecal samples were collected and analyzed using metagenomic sequencing. RESULTS: Liraglutide and semaglutide modulated both alpha and beta diversity of the gut microbiota in PCOS. Liraglutide increased the Bacillota-to-Bacteroidota ratio through up-regulating the abundance of butyrate-producing members of Bacillota like Lachnospiraceae. Moreover, liraglutide showed the ability to reverse the altered microbial composition and the disrupted microbiota functions caused by PCOS. Semaglutide increased the abundance of Helicobacter in PCOS mice (p < 0.01) which was the only bacteria found negatively correlated with body weight. Moreover, pathways involving porphyrin and flavonoids were increased after semaglutide intervention. CONCLUSION: Liraglutide and semaglutide improved reproductive and metabolic disorders by modulating the whole structure of gut microbiota in PCOS. The greater efficacy in weight loss compared with liraglutide observed after semaglutide intervention was positively related with Helicobacter. The study may provide new ideas in the treatment and the underlying mechanisms of GLP-1RAs to improve PCOS.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2025-1-30

Curated date: 2025/01/02

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

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
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 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy control group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Polycystic ovary syndrome group (PCOS)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Mice with Dehydroepiandrosterone (DHEA)-induced Polycystic ovary syndrome (PCOS).
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
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
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
LEfSe
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
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
3


Signature 1

Needs review

Curated date: 2025/01/03

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Source: Figure 3B

Description: LDA (linear discriminant analysis) scores for the species abundance in the control and PCOS groups.

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

NCBI Quality ControlLinks
Bacteroides acidifaciens
Duncaniella dubosii
Escherichia coli
Lepagella muris
Muribaculaceae bacterium
Paramuribaculum intestinale
unclassified Bacteroidales
unclassified Bacteroides
unclassified Enterobacteriaceae
Muribaculaceae bacterium Isolate-104 (HZI)
Muribaculaceae bacterium Isolate-110 (HZI)
Muribaculaceae bacterium Isolate-037 (Harlan)
Muribaculaceae bacterium Isolate-105 (HZI)
Barnesiella sp. CU968
Muribaculaceae bacterium Isolate-114 (HZI)
Muribaculaceae bacterium Isolate-004 (NCI)
Muribaculaceae bacterium Isolate-036 (Harlan)

Revision editor(s): Victoria, WikiWorks

Signature 2

Needs review

Curated date: 2025/01/03

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Source: Figure 3B

Description: LDA (linear discriminant analysis) scores for the species abundance in the control and PCOS groups.

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

NCBI Quality ControlLinks
bacterium 1xD42-87
Lachnospiraceae bacterium MD335
Lachnospiraceae bacterium
Muribaculum intestinale
Taurinivorans muris
Alistipes muris
Lachnospiraceae bacterium 10-1
Lachnospiraceae bacterium A4
bacterium 0.1xD8-71
Caudoviricetes sp.
Acetatifactor muris
unclassified Helicobacter
Lachnospiraceae bacterium 28-4
Acetatifactor aquisgranensis
Flintibacter muris
Sporofaciens musculi
Muribaculaceae bacterium Isolate-042 (Harlan)
Schaedlerella arabinosiphila
Oscillibacter sp. CU971
Oscillibacter sp. 1-3
unclassified Eubacteriales
Firmicutes bacterium ASF500
Eubacterium sp. 14-2
Eubacterium plexicaudatum
Helicobacter sp. MIT 03-1616

Revision editor(s): Victoria, WikiWorks

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2025-1-30

Curated date: 2025/01/02

Curator:

Revision editor(s):

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Polycystic ovary syndrome (PCOS) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Polycystic ovary syndrome + Liraglutide group (PCOS + Liraglutide)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Mice with Dehydroepiandrosterone (DHEA)-induced Polycystic ovary syndrome (PCOS) and then treated with liraglitude GLP-1RAs for 4 weeks.

Lab analysis

Statistical Analysis

Alpha Diversity

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: 2025/01/03

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Source: Figure 3C

Description: LDA scores for the species abundance in the PCOS and PCOS+Liraglutide groups.

Abundance in Group 1: increased abundance in

NCBI Quality ControlLinks
Duncaniella dubosii
Lachnospiraceae bacterium A4
Lachnospiraceae bacterium
Helicobacter ganmani
Bifidobacterium pseudolongum
Eubacterium sp. 14-2
Ileibacterium valens
Lactobacillus johnsonii
bacterium 1xD42-87
Alistipes muris
Dorea sp. 5-2
Lachnospiraceae bacterium A2
Flintibacter muris
Acutalibacter muris
Lachnospiraceae bacterium 10-1
Oscillibacter sp. 1-3
Oscillibacter sp. CU971
Muribaculaceae bacterium Isolate-080 (Janvier)
unclassified Eubacteriales
Firmicutes bacterium ASF500
Schaedlerella arabinosiphila
Sporofaciens musculi
Pseudoflavonifractor sp. 60
Otoolea muris
Colidextribacter sp. OB.20
Petralouisia muris
bacterium 1xD42-67
Faecalibaculum rodentium
Lachnospiraceae bacterium 3-1
Acetatifactor muris
unclassified Lachnospiraceae

Revision editor(s): Victoria, WikiWorks

Signature 2

Needs review

Curated date: 2025/01/03

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Source: Figure 3C

Description: LDA scores for the species abundance in the PCOS and PCOS+Liraglutide groups.

Abundance in Group 1: decreased abundance in

NCBI Quality ControlLinks
Lepagella muris
Muribaculaceae bacterium
Muribaculaceae bacterium Isolate-110 (HZI)
Muribaculaceae bacterium Isolate-013 (NCI)
Muribaculaceae bacterium Isolate-002 (NCI)
Muribaculaceae bacterium Isolate-004 (NCI)
Muribaculaceae bacterium Isolate-104 (HZI)
Muribaculaceae bacterium Isolate-102 (HZI)
Muribaculaceae bacterium Isolate-105 (HZI)
Muribaculaceae bacterium Isolate-037 (Harlan)
unclassified Bacteroidales
Bacteroides acidifaciens
unclassified Duncaniella
Muribaculum sp. NM65_B17
unclassified Enterobacteriaceae
Paramuribaculum intestinale
Escherichia coli
Prevotella sp. MGM2
Duncaniella muris
Parabacteroides distasonis
unclassified Bacteroides
Duncaniella freteri
Bacteroides stercorirosoris
unclassified Parabacteroides
Muribaculum gordoncarteri

Revision editor(s): Victoria, WikiWorks

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2025-1-30

Curated date: 2025/01/02

Curator:

Revision editor(s):

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Polycystic ovary syndrome + Semaglutide group (PCOS + Semaglutide)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Mice with Dehydroepiandrosterone (DHEA)-induced Polycystic ovary syndrome (PCOS) and then treated with Semaglutide GLP-1RAs for 4 weeks.

Lab analysis

Statistical Analysis

Alpha Diversity

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: 2025/01/03

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Source: Figure 3D

Description: LDA scores for the species abundance in the PCOS and PCOS+Semaglutide groups.

Abundance in Group 1: increased abundance in

NCBI Quality ControlLinks
unclassified Duncaniella
unclassified Helicobacter
Alistipes muris
Helicobacter sp. MIT 03-1616
Helicobacter typhlonius
Helicobacter japonicus
Faecalibaculum rodentium
Otoolea muris
Rikenella microfusus
Lachnospiraceae bacterium M18-1
Clostridium sp. MD294
Millionella massiliensis
Helicobacter hepaticus
Helicobacter sp. MIT 03-1614
unclassified Desulfovibrio
Senimuribacter intestinalis

Revision editor(s): Victoria, WikiWorks

Signature 2

Needs review

Curated date: 2025/01/03

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Source: Figure 3D

Description: LDA scores for the species abundance in the PCOS and PCOS+Semaglutide groups.

Abundance in Group 1: decreased abundance in

NCBI Quality ControlLinks
Acetivibrio sp. MSJd-27
Akkermansia muciniphila
Akkermansia muciniphila CAG:154
Alistipes communis
Alistipes finegoldii
Alistipes ihumii
Alistipes senegalensis
Alistipes sp. CAG:268
Bacteroidaceae bacterium
Bacteroidales bacterium
Bacteroides acidifaciens
Bacteroides faecichinchillae
Bacteroides finegoldii
Bacteroides nordii
Bacteroides ovatus
Bacteroides sp. CAG:927
Bacteroides stercorirosoris
Bacteroides uniformis
Bacteroides xylanisolvens
Blautia pseudococcoides
Burkholderiales bacterium
Escherichia coli
Muribaculaceae bacterium
Muribaculaceae bacterium Isolate-002 (NCI)
Muribaculaceae bacterium Isolate-037 (Harlan)
Muribaculaceae bacterium Isolate-110 (HZI)
Muribaculum intestinale
Odoribacter splanchnicus
Parabacteroides distasonis
Parabacteroides goldsteinii
Parabacteroides gordonii
Paraprevotella clara
Paraprevotella xylaniphila
Parasutterella excrementihominis
Phocaeicola sartorii
Phocaeicola vulgatus
Prevotella sp. CAG:1185
Prevotella sp. MGM2
Proteus mirabilis
Romboutsia ilealis
Segatella copri
Tannerella forsythia
unclassified Bacillota
unclassified Bacteroidales
unclassified Bacteroides
unclassified Enterobacterales
unclassified Enterobacteriaceae
unclassified Escherichia
unclassified Gammaproteobacteria
unclassified Parabacteroides
unclassified Proteus (in: enterobacteria)
unclassified Rikenellaceae
unclassified Turicibacter
Alistipes timonensis
unclassified Bacteroidaceae
Parabacteroides chinchillae
Gallalistipes aquisgranensis
Marseilla massiliensis
uncultured bacterium BAC10G6
Intestinimonas massiliensis (ex Liu et al. 2021)
Alistipes sp. An66
Candidatus Contubernalis alkalaceticus
Lawsonibacter celer

Revision editor(s): Victoria, WikiWorks

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2025-1-30

Curated date: 2025/01/14

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy control group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Polycystic ovary syndrome group (PCOS)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Mice with Dehydroepiandrosterone (DHEA)-induced Polycystic ovary syndrome (PCOS).

Lab analysis

Statistical Analysis

Statistical test
Kruskall-Wallis
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified


Signature 1

Needs review

Curated date: 2025/01/14

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Source: Figure 2b, c, d & Figure 3e

Description: Microbiota composition at the phylum, family, and genus level and the relative abundance of signatures among four groups.

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

NCBI Quality ControlLinks
Muribaculaceae bacterium Isolate-037 (Harlan)
Bacteroidota
Muribaculaceae
Bacteroidaceae
Bacteroides
Lepagella muris
Lepagella
Bacteroides acidifaciens

Revision editor(s): Victoria, WikiWorks

Signature 2

Needs review

Curated date: 2025/01/14

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Source: Figure 2b

Description: Microbiota composition at the phylum, family, and genus level and the relative abundance of signatures among four groups.

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

NCBI Quality ControlLinks
Bacillota
Bacillota/BacteroidotaBacillota/Bacteroidota

Revision editor(s): Victoria, WikiWorks

Experiment 5


Reviewed Marked as Reviewed by Svetlana up on 2025-1-30

Curated date: 2025/01/14

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Polycystic ovary syndrome (PCOS) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Polycystic ovary syndrome + Liraglutide group (PCOS + Liraglutide)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Mice with Dehydroepiandrosterone (DHEA)-induced Polycystic ovary syndrome (PCOS) and then treated with liraglutide GLP-1RAs for 4 weeks.

Lab analysis

Statistical Analysis

Alpha Diversity

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: 2025/01/14

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Source: Figure 2b, c & d

Description: Microbiota composition at the phylum, family, and genus level and the relative abundance of signatures among four groups.

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

NCBI Quality ControlLinks
Bacillota
Bifidobacterium
Ileibacterium
Lachnospiraceae
Oscillospiraceae
Bacillota/BacteroidotaBacillota/Bacteroidota

Revision editor(s): Victoria, WikiWorks

Signature 2

Needs review

Curated date: 2025/01/14

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Source: Figure 2b, c, d & Figure 3e

Description: Microbiota composition at the phylum, family, and genus level and the relative abundance of signatures among four groups.

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

NCBI Quality ControlLinks
Muribaculaceae bacterium Isolate-037 (Harlan)
Bacteroidota
Muribaculaceae
Bacteroidaceae
Lepagella
Bacteroides
Lepagella muris
Bacteroides acidifaciens

Revision editor(s): Victoria, WikiWorks

Experiment 6


Reviewed Marked as Reviewed by Svetlana up on 2025-1-30

Curated date: 2025/01/14

Curator:

Revision editor(s):

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Polycystic ovary syndrome + Semaglutide group (PCOS + Semaglutide)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Mice with Dehydroepiandrosterone (DHEA)-induced Polycystic ovary syndrome (PCOS) and then treated with Semaglutide GLP-1RAs for 4 weeks.

Lab analysis

Statistical Analysis

Alpha Diversity

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: 2025/01/14

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Source: Figure 2b, c, d & Figure 3e

Description: Microbiota composition at the phylum, family, and genus level and the relative abundance of signatures among four groups.

Abundance in Group 1: increased abundance in

NCBI Quality ControlLinks
Campylobacterota
Helicobacteraceae
Helicobacter
Alistipes muris

Revision editor(s): Victoria, WikiWorks

Signature 2

Needs review

Curated date: 2025/01/14

Curator: Victoria

Revision editor(s): Victoria, WikiWorks

Source: Figure 2d & Figure 3e

Description: Microbiota composition at the phylum, family, and genus level and the relative abundance of signatures among four groups.

Abundance in Group 1: decreased abundance in

NCBI Quality ControlLinks
Lepagella
Bacteroides
Lepagella muris
Bacteroides acidifaciens
Muribaculaceae bacterium Isolate-037 (Harlan)

Revision editor(s): Victoria, WikiWorks