Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling

From BugSigDB
Reviewed Marked as Reviewed by KateRasheed on 2025-8-18
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Li S, Zhai J, Chu W, Geng X, Wang D, Jiao L, Lu G, Chan WY, Sun K, Sun Y, Chen ZJ, Du Y
Journal
NPJ biofilms and microbiomes
Year
2023
Knowledge gaps that limit the development of therapies for polycystic ovary syndrome (PCOS) concern various environmental factors that impact clinical characteristics. Circadian dysrhythmia contributes to glycometabolic and reproductive hallmarks of PCOS. Here, we illustrated the amelioration of Limosilactobacillus reuteri (L. reuteri) on biorhythm disorder-ignited dyslipidemia of PCOS via a microbiota-metabolite-liver axis. A rat model of long-term (8 weeks) darkness treatment was used to mimic circadian dysrhythmia-induced PCOS. Hepatic transcriptomics certified by in vitro experiments demonstrated that increased hepatic galanin receptor 1 (GALR1) due to darkness exposure functioned as a critical upstream factor in the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway to suppress nuclear receptors subfamily 1, group D, member 1 (NR1D1) and promoted sterol regulatory element binding protein 1 (SREBP1), inducing lipid accumulation in the liver. Further investigations figured out a restructured microbiome-metabolome network following L. reuteri administration to protect darkness rats against dyslipidemia. Notably, L. reuteri intervention resulted in the decrease of Clostridium sensu stricto 1 and Ruminococcaceae UCG-010 as well as gut microbiota-derived metabolite capric acid, which could further inhibit GALR1-NR1D1-SREBP1 pathway in the liver. In addition, GALR antagonist M40 reproduced similar ameliorative effects as L. reuteri to protect against dyslipidemia. While exogenous treatment of capric acid restrained the protective effects of L. reuteri in circadian disruption-induced PCOS through inhibiting GALR1-dependent hepatic lipid metabolism. These findings purport that L. reuteri could serve for circadian disruption-associated dyslipidemia. Manipulation of L. reuteri-capric acid-GALR1 axis paves way for clinical therapeutic strategies to prevent biorhythm disorder-ignited dyslipidemia in PCOS women.

Experiment 1


Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/08/06

Curator: Victoria

Revision editor(s): Victoria, Ese

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
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
Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Darkness
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Rats in this group were exposed to the darkness treatment for 8 weeks.
Group 0 sample size Number of subjects in the control (unexposed) group
8
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
Dunn's test
Kruskall-Wallis
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
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 2025-8-18

Curated date: 2025/08/06

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5c & Supplementary Data 4

Description: Relative abundance of differential genera (highly or lowly expressed in darkness rats compared with control and DL.reuteri rats, P < 0.05), calculated with Kruskal–Wallis test followed by Dunn’s multiple comparison test.

Abundance in Group 1: increased abundance in Darkness

NCBI Quality ControlLinks
Clostridium
Ruminococcaceae UCG-009Ruminococcaceae UCG-009
Ruminococcaceae UCG-010Ruminococcaceae UCG-010
Family XIII AD3011 groupFamily XIII AD3011 group

Revision editor(s): Victoria

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/08/06

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5c & Supplementary Data 4

Description: Relative abundance of differential genera (highly or lowly expressed in darkness rats compared with control and DL.reuteri rats, P < 0.05), calculated with Kruskal–Wallis test followed by Dunn’s multiple comparison test.

Abundance in Group 1: decreased abundance in Darkness

NCBI Quality ControlLinks
Lactobacillus

Revision editor(s): Victoria

Experiment 2


Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/08/06

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
Darkness
Group 1 name Corresponds to the case (exposed) group for case-control studies
Darkness+Limosilactobacillus reuteri
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Rats in this group were exposed to the darkness treatment for 8 weeks, followed by Limosilactobacillus reuteri administration.

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 2025-8-18

Curated date: 2025/08/06

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5c & Supplementary Data 4

Description: Relative abundance of differential genera (highly or lowly expressed in darkness rats compared with control and DL.reuteri rats, P < 0.05), calculated with Kruskal–Wallis test followed by Dunn’s multiple comparison test.

Abundance in Group 1: increased abundance in Darkness+Limosilactobacillus reuteri

NCBI Quality ControlLinks
Lactobacillus

Revision editor(s): Victoria

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/08/06

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5c & Supplementary Data 4

Description: Relative abundance of differential genera (highly or lowly expressed in darkness rats compared with control and DL.reuteri rats, P < 0.05), calculated with Kruskal–Wallis test followed by Dunn’s multiple comparison test.

Abundance in Group 1: decreased abundance in Darkness+Limosilactobacillus reuteri

NCBI Quality ControlLinks
Clostridium
Ruminococcaceae UCG-009Ruminococcaceae UCG-009
Ruminococcaceae UCG-010Ruminococcaceae UCG-010
Family XIII AD3011 groupFamily XIII AD3011 group

Revision editor(s): Victoria

Experiment 3


Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/08/06

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 & Darkness
Group 0 sample size Number of subjects in the control (unexposed) group
16

Lab analysis

Statistical Analysis

Statistical test
LEfSe
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2


Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/08/06

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5d & e

Description: Cladogram and Genera biomarkers within groups identified by LDA effect size analysis with an LDA score > 2.

Abundance in Group 1: increased abundance in Darkness+Limosilactobacillus reuteri

NCBI Quality ControlLinks
Butyricimonas
Candidatus Gastranaerophilales
Candidatus Melainabacteria
Candidatus Neoarthromitus
Eubacterium ruminantium
Mollicutes
Streptococcaceae
Streptococcus
uncultured Erysipelotrichia bacterium
uncultured rumen bacterium
Ruminococcus 2Ruminococcus 2
Prevotella 1Prevotella 1
Mollicutes RF9Mollicutes RF9
uncultured Oscillospiraceae bacterium

Revision editor(s): Victoria

Experiment 4


Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/08/06

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 & Darkness+Limosilactobacillus reuteri
Group 1 name Corresponds to the case (exposed) group for case-control studies
Darkness
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Rats in this group were exposed to the darkness treatment for 8 weeks.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/08/06

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5d & e

Description: Cladogram and Genera biomarkers within groups identified by LDA effect size analysis with an LDA score > 2.

Abundance in Group 1: increased abundance in Darkness

NCBI Quality ControlLinks
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Clostridium
Erysipelotrichaceae
Erysipelotrichales
Erysipelotrichia
Faecalitalea
Oscillibacter
Pasteurella
Pasteurellaceae
Pasteurellales
Peptostreptococcaceae
Turicibacter
Ruminococcaceae UCG-010Ruminococcaceae UCG-010
Ruminiclostridium 5Ruminiclostridium 5
Ruminococcaceae UCG-009Ruminococcaceae UCG-009
Family XIIIFamily XIII
Clostridiaceae 1Clostridiaceae 1
Family XIII AD3011 groupFamily XIII AD3011 group

Revision editor(s): Victoria

Experiment 5


Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/08/06

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
Darkness & Darkness+Limosilactobacillus reuteri
Group 1 name Corresponds to the case (exposed) group for case-control studies
Control
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Rats in this group were not exposed to the darkness treatment.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/08/06

Curator: Victoria

Revision editor(s): Victoria

Source: Figure 5d & e

Description: Cladogram and Genera biomarkers within groups identified by LDA effect size analysis with an LDA score > 2.

Abundance in Group 1: increased abundance in Control

NCBI Quality ControlLinks
Corynebacterium 1Corynebacterium 1
Atopostipes
Sporosarcina
Jeotgalicoccus
Facklamia
Bacillus
Psychrobacter
Vagococcus
Myroides
Amphibacillus
Mesohizorbium sp. UASWS1009Mesohizorbium sp. UASWS1009
Brachybacterium
Oceanobacillus
Bacilli
Lactobacillales
Carnobacteriaceae
Aerococcaceae
Caryophanaceae
Bacillaceae
Flavobacteriia
Flavobacteriaceae
Flavobacteriales
Actinomycetota
Dermabacteraceae
Mycobacteriales
Corynebacteriaceae

Revision editor(s): Victoria