Gut microbiota dysbiosis promotes coronary heart disease comorbid with depression through lipopolysaccharides and Toll-like receptor 4
From BugSigDB
Jump to:navigation, search
Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Pan Y., Luo Y., Wu G., Lu Y., Yang P., Kong P., Zheng C., Wang C., Yang L., Li X.
Journal
BMC microbiology
Year
2025
Keywords:
Coronary heart disease, Depression, Gut microbiota, Lipopolysaccharides, TLR4 receptors
Coronary heart disease (CHD) and depression often coexist and complicate patient care. The gut microbiota plays a crucial role in overall health and is involved in both conditions. Dysbiosis, particularly, increased levels of lipopolysaccharides (LPSs), can activate the Toll-like receptor 4 (TLR4), triggering inflammatory pathways associated with CHD and depression. Although some associations have been observed, the direct mechanistic association among gut dysbiosis, LPSs, TLR4 activation, and comorbidity of CHD and depression remains unclear. Thus, in the present study, we aimed to explore this association and the potential of modulating gut microbiota as a therapeutic strategy. METHODS: A rat model of CHD and depression was established using a high-fat diet and chronic unpredictable mild stress and verified by electrocardiogram, behavioral assessments, and cardiac marker analysis. Fecal microbiota transplantation (FMT) was performed by transferring microbiota from diseased rats to healthy rats (FMT-Disease group); the fecal microbiota of the rats from the FMT-Disease and FMT-Normal groups were compared. The TLR4 inhibitor TAK-242 was administered, creating the Disease + TAK-242 and FMT-Disease-TAK-242 groups. Gut microbiota composition was analyzed using 16 S rRNA high-throughput sequencing; LPS levels were measured using enzyme-linked immunosorbent assay. Polymerase chain reaction and western blotting were used to detect the expression of genes and proteins related to the TLR4/MYD88/NF-κB pathway in the heart and hippocampus, respectively. RESULTS: We confirmed that in the FMT-Disease group, the gut microbiota of diseased rats altered the gut microbial composition of healthy rats in terms of β-diversity, α-diversity, and community structure. Notably, LPS levels in the serum of FMT-Disease rats were elevated, thereby activating the TLR4/MYD88/NF-κB inflammatory pathway and increasing susceptibility to CHD comorbid with depression. Additionally, after receiving fecal microbiota from healthy rats, the Disease group showed a restoration of gut microbiota balance, improvement in general condition, and normalization of pathological, biochemical, and inflammatory indicators, indicating a suppressive effect on the progression of CHD with depression. CONCLUSION: Our findings further clarify the interrelationship between gut microbiota and CHD comorbid with depression, enhancing our understanding of its pathogenesis. Moreover, we propose a potential novel therapeutic strategy that focuses on modulating gut microbiota composition to block the TLR4/MYD88/NF-κB inflammatory pathway.
Experiment 1
Needs review
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 transplant Response to transplant,response to transplant
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy rats receiving autologous fecal matter transplant
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Healthy rats receiving fecal matter transplant from diseased rats
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Healthy rats receiving fecal microbiota transplantation from rats with coronary heart disease comorbid with depression (CHDWD), leading to altered gut microbiota composition and development of disease-like symptoms including weight loss, decreased appetite, and depressive behaviors
- Group 0 sample size Number of subjects in the control (unexposed) group
- 7
- Group 1 sample size Number of subjects in the case (exposed) group
- 7
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
- Mann-Whitney (Wilcoxon)
- 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)?
- No
Signature 1
Needs review
Source: Figure 3, Table 2
Description: Increased in Group 1 (Fecal matter transplant-Disease compared to Fecal matter transplant-Normal)
Abundance in Group 1: increased abundance in Healthy rats receiving fecal matter transplant from diseased rats
Revision editor(s): Nina Takang
Signature 2
Needs review
Source: Figure 3, Table 2
Description: Decreased in Group 1 (Fecal matter transplant-Disease compared to Fecal matter transplant-Normal)
Abundance in Group 1: decreased abundance in Healthy rats receiving fecal matter transplant from diseased rats
Revision editor(s): Nina Takang
Experiment 2
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Coronary artery disease , Depressive disorder Arterioscleroses, Coronary,Arteriosclerosis, Coronary,Artery Disease, Coronary,Artery Diseases, Coronary,Atheroscleroses, Coronary,Atherosclerosis, Coronary,CAD,CHD,CHD (coronary heart disease),CHD - Coronary heart disease,Coronary Arterioscleroses,Coronary Arteriosclerosis,coronary arteriosclerosis,CORONARY ARTERY DIS,Coronary Artery Disease,coronary artery disease,coronary artery disease or disorder,Coronary Artery Diseases,Coronary Atheroscleroses,Coronary Atherosclerosis,CORONARY DIS,Coronary Disease,coronary disease,Coronary Diseases,CORONARY HEART DIS,coronary heart disease,Coronary Heart Diseases,disease of coronary artery,disease or disorder of coronary artery,Disease, Coronary,Disease, Coronary Artery,Disease, Coronary Heart,Diseases, Coronary,Diseases, Coronary Artery,Diseases, Coronary Heart,disorder of coronary artery,Heart Disease, Coronary,Heart Diseases, Coronary,Coronary artery disease,depression,melancholia,melancholias,mental depression,syndrome, depressive,syndromes, depressive,Depressive disorder,depressive disorder
- 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
- Diseased model
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Male Sprague–Dawley rats that were used to establish a model of coronary heart disease comorbid with depression (CHDWD). The model was induced through a high-fat diet, chronic unpredictable mild stress (CUMS), and a coronary artery ligation surgery. Rats that met the predefined diagnostic criteria were considered successfully modeled.
Signature 1
Source: Table 1, Figure 2b, Text in Results - CHDWD altered gut microbiota composition
Description: Table showing the significant differences and direction of the genera in the control and CHDWD model. Figure showing barplots of the differential abundance in phyla.
Abundance in Group 1: increased abundance in Diseased model
Revision editor(s): YokoC
Signature 2
Source: Table 1
Description: Table showing the significant differences and direction of the genera in the control and CHDWD model.
Abundance in Group 1: decreased abundance in Diseased model
Revision editor(s): YokoC
Retrieved from "https://bugsigdb.org/w/index.php?title=40999363&oldid=214033"
