Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Yang J, Wang E, Jiang M, Tan Y, Yao F, Sun C, Pan L, Gao L, Yao J
Journal
Journal of ovarian research
Year
2023
Keywords:
Gut microbiota, Metabolomics, Obesity, Orlistat, Polycystic ovary syndrome
BACKGROUND: This study aimed to compare the characteristics of the gut microbiota and their metabolite profiles between polycystic ovary syndrome (PCOS) and orlistat-treated PCOS rats (ORL-PCOS), which could help to better understand the underlying mechanism of the effect of orlistat on PCOS. METHODS: PCOS rat models were established using letrozole combined with a high-fat diet. Ten rats were randomly selected as a PCOS control group (PCOS). The other three groups (n = 10/group) were additionally supplemented with different doses of orlistat (low, medium, high). Then, fecal samples of the PCOS and ORL-PCOS groups were analysed by 16S rRNA gene sequencing and untargeted metabolomics. Blood samples were collected to detect serum sex hormones and lipids. RESULTS: The results showed that orlistat attenuated the body weight gain, decreased the levels of T, LH, the LH/FSH ratio, TC, TG and LDL-C; increased the level of E2; and improved estrous cycle disorder in PCOS rats. The bacterial richness and diversity of the gut microbiota in the ORL-PCOS group were higher than those in the PCOS group. The ratio of Firmicutes to Bacteroidetes was decreased with orlistat treatment. Moreover, orlistat treatment led to a significant decrease in the relative abundance of Ruminococcaceae and Lactobacillaceae, and increases in the abundances of Muribaculaceae and Bacteroidaceae. Metabolic analysis identified 216 differential fecal metabolites in total and 6 enriched KEGG pathways between the two groups, including steroid hormone biosynthesis, neuroactive ligand-receptor interaction and vitamin digestion and absorption. Steroid hormone biosynthesis was the pathway with the most significant enrichment. The correlations between the gut microbiota and differential metabolites were calculated, which may provide a basis for understanding the composition and function of microbial communities. CONCLUSIONS: Our data suggested that orlistat exerts a PCOS treatment effect, which may be mediated by modifying the structure and composition of the gut microbiota, as well as the metabolite profiles of PCOS rats.

Experiment 1


Needs review

Curated date: 2025/04/30

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke

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
Treatment outcome measurement Treatment outcome measurement,treatment outcome measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
PCOS (Polycystic ovary syndrome ) Control group
Group 1 name Corresponds to the case (exposed) group for case-control studies
ORL-PCOS (Orlistat-Polycystic ovary syndrome) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The ORL-PCOS (Orlistat-Polycystic ovary syndrome) group was treated with different doses of orlistat (low-20 mg/kg/d; medium-40 mg/kg/d; high-80 mg/kg/d; Lunan Pharmaceutical Group Corporation; Shandong, Linyi, China.) over the next 12 weeks.
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

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
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

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/04/30

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke, Victoria

Source: Fig. 4A and 4B

Description: LEfSe of the gut microbiota of the ORL-PCOS and PCOS groups.

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

NCBI Quality ControlLinks
Acidibacter
Acidimicrobiia
Acidobacteriota
Acidothermaceae
Acidothermus
Alphaproteobacteria
Anaeromyxobacter
Aquicella
Aquisphaera
Bacteroidaceae
Bacteroidales
Bacteroides
Bacteroidia
Bacteroidota
Bryobacter
Butyricimonas
Candidatus Korobacter
Candidatus Solibacter
Desulfovibrio
Frankiales
Gemmatirosa
Hyphomicrobiales
Methanocella
Muribaculaceae
Mycobacterium
Occallatibacter
Parabacteroides
Parasutterella
Pseudomonadota
Roseiarcus
Terriglobia
Xanthobacteraceae
mouse gut metagenome
uncultured Acidobacteriota bacterium
uncultured Actinomycetes bacterium
uncultured Alphaproteobacteria bacterium
uncultured Bacillota bacterium
uncultured bacterium
uncultured forest soil bacterium
Ruminococcaceae_NK4A214_groupRuminococcaceae_NK4A214_group

Revision editor(s): PreciousChijioke, Victoria

Signature 2

Needs review

Curated date: 2025/05/01

Curator: PreciousChijioke

Revision editor(s): PreciousChijioke

Source: Fig. 4A and 4B

Description: LEfSe of the gut microbiota of the ORL-PCOS and PCOS groups.

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

NCBI Quality ControlLinks
Bacilli
Bacillota
Lactobacillaceae
Lactobacillales
Lactobacillus
Oscillospiraceae
Ruminococcaceae_UCG_005Ruminococcaceae_UCG_005
Ruminococcaceae_UCG_014Ruminococcaceae_UCG_014
Eubacterium coprostanoligenes
Ruminococcus 2Ruminococcus 2
Ruminiclostridium 6Ruminiclostridium 6
Ruminococcaceae UCG-010Ruminococcaceae UCG-010
Ruminococcaceae UCG-008Ruminococcaceae UCG-008
GCA-900066225GCA-900066225
Ruminococcaceae UCG-009Ruminococcaceae UCG-009
Butyricicoccus
Defluvitalaceae UCG-011Defluvitalaceae UCG-011
Erysipelotrichaceae UCG-003Erysipelotrichaceae UCG-003

Revision editor(s): PreciousChijioke