Modulatory impact of Bifidobacterium longum subsp. longum BL21 on the gut-brain-ovary axis in polycystic ovary syndrome: insights into metabolic regulation, inflammation mitigation, and neuroprotection

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
Dong Y, Yang S, Zhang S, Zhao Y, Li X, Han M, Gai Z, Zou K
Journal
mSphere
Year
2025
Keywords:
Bifidobacterium longum subsp. longum, gut–brain–ovary axis, inflammation mitigation, metabolic regulation, polycystic ovarian syndrome
This study evaluates the efficacy of Bifidobacterium longum subsp. longum BL21 in mitigating symptoms of polycystic ovarian syndrome (PCOS) in DHT-induced PCOS model mice. It focuses on BL21's role in modulating metabolic dysregulation, inflammation, and neuroprotection via the gut-brain-ovary axis. Employing an 8-week treatment regimen, this research assessed the effects of BL21 on prenatal androgen-induced PCOS in ICR mice. Evaluations included body weight, glucose tolerance tests, serum analyses of BDNF, inflammatory markers, sex hormone levels, and 16S rRNA gene sequencing for gut microbiota diversity and composition. Twenty-four ICR mice with induced PCOS served as subjects to examine the probiotic's impact. Mice were administered a daily oral dose of 1 × 109 CFU of BL21 continuously for a total of 8 weeks. BL21 significantly enhanced sex hormone levels (P < 0.05), particularly those of follicle-stimulating hormone (FSH) and estradiol (E2), indicating improved ovarian function and offering a novel PCOS treatment approach. The intervention notably curbed weight gain and improved glucose tolerance in PCOS mice (P < 0.05). BL21 reduced inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and lipopolysaccharides (LPS), while increasing IL-10, BDNF, FSH, and E2 levels (P < 0.05 for all). It also enriched gut microbiota diversity, enhancing populations of Bifidobacterium and Lactobacillus. Correlation analyses underscored the positive shifts in microbiota linked to beneficial hormonal and inflammatory profiles. BL21 shows promise in alleviating PCOS symptoms through metabolic regulation, inflammation reduction, and neuroprotection, validating its potential in integrated therapeutic strategies.IMPORTANCEPolycystic ovarian syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, characterized by metabolic irregularities, hormonal imbalances, and chronic inflammation. Existing treatments are often inadequate, addressing symptoms without targeting the underlying etiological factors. The investigation of Bifidobacterium longum subsp. longum BL21 as a probiotic intervention offers a novel approach by potentially regulating the gut-brain-ovary axis. This could lead to innovative therapeutic strategies that not only manage but also potentially reverse the multifaceted symptoms of PCOS, enhancing quality of life and reproductive health.

Experiment 1


Needs review

Curated date: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria

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
Polycystic ovary syndrome (PCOS) + Bifidobacterium longum subsp. longum (BL21) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Control (CTL) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group consists of pregnant mice used as controls.
Group 0 sample size Number of subjects in the control (unexposed) group
16
Group 1 sample size Number of subjects in the case (exposed) group
8

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
2


Signature 1

Needs review

Curated date: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 6A

Description: Results of the linear discriminant analysis effect size (LEfSe) analysis, showing the impact of BL21 treatment on differences in the abundance of bacterial taxa at the genus level. LEfSe analysis evaluates each significantly enriched bacterial taxonomic unit by calculating linear discriminant analysis (LDA) scores.

Abundance in Group 1: increased abundance in Control (CTL) group

NCBI Quality ControlLinks
Parasutterella
Odoribacter
Bacteria incertae sedis
Colidextribacter
Helicobacter
Rs-E47 termite groupRs-E47 termite group

Revision editor(s): Victoria

Experiment 2


Needs review

Curated date: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Control (CTL) + Bifidobacterium longum subsp. longum (BL21) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Polycystic ovary syndrome (PCOS) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group consists of mice that were given dihydrotestosterone (DHT) to induce Polycystic ovary syndrome (PCOS).

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 6A

Description: Results of the linear discriminant analysis effect size (LEfSe) analysis, showing the impact of BL21 treatment on differences in the abundance of bacterial taxa at the genus level. LEfSe analysis evaluates each significantly enriched bacterial taxonomic unit by calculating linear discriminant analysis (LDA) scores.

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

NCBI Quality ControlLinks
Prevotellaceae UCG-001Prevotellaceae UCG-001
Alistipes
Alloprevotella
Klebsiella
Lachnospiraceae NK4A136 groupLachnospiraceae NK4A136 group
Rikenellaceae RC9 gut groupRikenellaceae RC9 gut group

Revision editor(s): Victoria

Experiment 3


Needs review

Curated date: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria, Ese

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Control (CTL) + Polycystic ovary syndrome (PCOS) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Bifidobacterium longum subsp. longum (BL21) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group consists of mice that were given dihydrotestosterone (DHT) to induce Polycystic ovary syndrome (PCOS) and then administered a daily oral dose of 1 × 109 CFU of BL21 continuously for a total of 8 weeks as treatment.

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 6A

Description: Results of the linear discriminant analysis effect size (LEfSe) analysis, showing the impact of BL21 treatment on differences in the abundance of bacterial taxa at the genus level. LEfSe analysis evaluates each significantly enriched bacterial taxonomic unit by calculating linear discriminant analysis (LDA) scores.

Abundance in Group 1: increased abundance in Bifidobacterium longum subsp. longum (BL21) group

NCBI Quality ControlLinks
Bacteroides
Butyricicoccus
Lachnospiraceae UCG-010Lachnospiraceae UCG-010
Muribaculum
Muribaculaceae
Lactobacillus
Bifidobacterium
Rikenella
Blautia
Actinomyces

Revision editor(s): Victoria

Experiment 4


Needs review

Curated date: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Control (CTL) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Polycystic Ovary Syndrome (PCOS) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group consists of mice that were given dihydrotestosterone (DHT) to induce Polycystic ovary syndrome (PCOS)—pre-BL21 intervention.
Group 0 sample size Number of subjects in the control (unexposed) group
8

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: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 6B

Description: LEfSe analysis results at the genus level between the DHT-induced PCOS mouse model and the control (CTL) group.

Abundance in Group 1: increased abundance in Polycystic Ovary Syndrome (PCOS) group

NCBI Quality ControlLinks
Rikenellaceae RC9 gut groupRikenellaceae RC9 gut group
UCG-010UCG-010
Rikenella
Prevotellaceae UCG-001Prevotellaceae UCG-001
Muribaculaceae
Lachnospiraceae NK4A136 groupLachnospiraceae NK4A136 group
Candidatus Neoarthromitus
Helicobacter
Bacteroides
Alloprevotella
Eubacterium xylanophilum
Eubacterium coprostanoligenes

Revision editor(s): Victoria

Signature 2

Needs review

Curated date: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 6B

Description: LEfSe analysis results at the genus level between the DHT-induced PCOS mouse model and the control (CTL) group.

Abundance in Group 1: decreased abundance in Polycystic Ovary Syndrome (PCOS) group

NCBI Quality ControlLinks
Parabacteroides
UCG-009UCG-009
Rs-E47 termite groupRs-E47 termite group
Odoribacter
Lactobacillus
Bifidobacterium
Desulfovibrio
Alistipes

Revision editor(s): Victoria

Experiment 5


Needs review

Curated date: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria, Ese

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
Bifidobacterium longum subsp. longum (BL21) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group consists of mice that were given dihydrotestosterone (DHT) to induce Polycystic ovary syndrome (PCOS) and then administered a daily oral dose of 1 × 109 CFU of BL21 continuously for a total of 8 weeks as treatment.—post-BL21 intervention.

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 6C

Description: Post-intervention LEfSe analysis results at the genus level between the DHT-induced PCOS mouse model and the BL21 treatment group.

Abundance in Group 1: increased abundance in Bifidobacterium longum subsp. longum (BL21) group

NCBI Quality ControlLinks
Ruminococcus
Rikenella
Lactobacillus
Lachnospiraceae NK4A136 groupLachnospiraceae NK4A136 group
Bifidobacterium
Bacteroides

Revision editor(s): Victoria

Signature 2

Needs review

Curated date: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 6C

Description: Post-intervention LEfSe analysis results at the genus level between the DHT-induced PCOS mouse model and the BL21 treatment group.

Abundance in Group 1: decreased abundance in Bifidobacterium longum subsp. longum (BL21) group

NCBI Quality ControlLinks
Odoribacter
Lachnoclostridium
Muribaculaceae
Helicobacter
Alistipes

Revision editor(s): Victoria

Experiment 6


Needs review

Curated date: 2025/07/07

Curator: Victoria

Revision editor(s): Victoria, Ese

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Bifidobacterium longum subsp. longum (BL21_Baseline) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Bifidobacterium longum subsp. longum (BL21_End) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group consists of mice that were given dihydrotestosterone (DHT) to induce Polycystic ovary syndrome (PCOS) and then administered a daily oral dose of 1 × 109 CFU of BL21 continuously for a total of 8 weeks as treatment (after BL21 intervention).

Lab analysis

Statistical Analysis

Statistical test
Kruskall-Wallis
Mann-Whitney (Wilcoxon)
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: 2025/07/08

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5B

Description: Violin plots illustrating differences in gut microbiota abundance at the phylum level before and after BL21 intervention at different time points. Different letters indicate statistically significant differences between groups.

Abundance in Group 1: increased abundance in Bifidobacterium longum subsp. longum (BL21_End) group

NCBI Quality ControlLinks
Thermodesulfobacteriota

Revision editor(s): Victoria

Experiment 7


Needs review

Curated date: 2025/07/08

Curator: Victoria

Revision editor(s): Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Control (CTL_Baseline) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Control (CTL_End) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group consists of pregnant mice used as controls (after BL21 intervention)

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
Kruskall-Wallis


Signature 1

Needs review

Curated date: 2025/07/08

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5B

Description: Violin plots illustrating differences in gut microbiota abundance at the phylum level before and after BL21 intervention at different time points.

Abundance in Group 1: increased abundance in Control (CTL_End) group

NCBI Quality ControlLinks
Thermodesulfobacteriota
Campylobacterota

Revision editor(s): Victoria

Signature 2

Needs review

Curated date: 2025/07/08

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5B

Description: Violin plots illustrating differences in gut microbiota abundance at the phylum level before and after BL21 intervention at different time points.

Abundance in Group 1: decreased abundance in Control (CTL_End) group

NCBI Quality ControlLinks
Pseudomonadota

Revision editor(s): Victoria

Experiment 8


Needs review

Curated date: 2025/07/08

Curator: Victoria

Revision editor(s): Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Polycystic Ovary Syndrome (PCOS_Baseline) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Polycystic Ovary Syndrome (PCOS_End) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
This group consists of mice that were given dihydrotestosterone (DHT) to induce Polycystic ovary syndrome (PCOS) (after BL21 intervention).

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/07/08

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5B

Description: Violin plots illustrating differences in gut microbiota abundance at the phylum level before and after BL21 intervention at different time points. Different letters indicate statistically significant differences between groups.

Abundance in Group 1: increased abundance in Polycystic Ovary Syndrome (PCOS_End) group

NCBI Quality ControlLinks
Thermodesulfobacteriota

Revision editor(s): Victoria

Signature 2

Needs review

Curated date: 2025/07/08

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5B

Description: Violin plots illustrating differences in gut microbiota abundance at the phylum level before and after BL21 intervention at different time points. Different letters indicate statistically significant differences between groups.

Abundance in Group 1: decreased abundance in Polycystic Ovary Syndrome (PCOS_End) group

NCBI Quality ControlLinks
Campylobacterota
Bacillota

Revision editor(s): Victoria