Predominance of Escherichia-Shigella in Gut Microbiome and Its Potential Correlation with Elevated Level of Plasma Tumor Necrosis Factor Alpha in Patients with Tuberculous Meningitis
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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
Authors
Li S, Guo J, Liu R, Zhang F, Wen S, Liu Y, Ren W, Zhang X, Shang Y, Gao M, Lu J, Pang Y
Journal
Microbiology spectrum
Year
2022
Keywords:
Escherichia-Shigella, TNF-α, claudin-5, gut microbiota, tuberculous meningitis
Tuberculous meningitis (TBM), the most lethal and disabling form of tuberculosis (TB), may be related to gut microbiota composition, warranting further study. Here we systematically compared gut microbiota compositions and blood cytokine profiles of TBM patients, pulmonary TB patients, and healthy controls. Notably, the significant gut microbiota dysbiosis observed in TBM patients was associated with markedly high proportions of Escherichia-Shigella species as well as increased blood levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Next, we obtained a fecal bacterial isolate from a TBM patient and administered it via oral gavage to mice in order to develop a murine gut microbiota dysbiosis model for use in exploring mechanisms underlying the observed relationship between gut microbial dysbiosis and TBM. Thereafter, cells of commensal Escherichia coli (E. coli) were isolated and administered to model mice by gavage and then mice were inoculated with Mycobacterium tuberculosis (M. tuberculosis). Subsequently, these mice exhibited increased blood TNF-α levels accompanied by downregulated expression of tight junction protein claudin-5, increased brain tissue bacterial burden, and elevated central nervous system inflammation relative to corresponding indicators in controls administered PBS by gavage. Thus, our results demonstrated that a signature dysbiotic gut microbiome profile containing a high proportion of E. coli was potentially associated with an increased circulating TNF-α level in TBM patients. Collectively, these results suggest that modulation of dysbiotic gut microbiota holds promise as a new strategy for preventing or alleviating TBM. IMPORTANCE As the most severe form of tuberculosis, the pathogenesis of tuberculous meningitis (TBM) is still unclear. Gut microbiota dysbiosis plays an important role in a variety of central nervous system diseases. However, the relationship between gut microbiota and TBM has not been identified. In our study, significant dysbiosis in gut microbiota composition with a high proportion of E. coli and increased levels of TNF-α in plasma was noted in TBM patients. A commensal E. coli was isolated and shown to increase the plasma level of TNF-α and downregulate brain tight junction protein claudin-5 in the murine model. Gavage administration of E. coli aggravated the bacterial burden and increased the inflammatory responses in the central nervous system after M. tuberculosis infection. Dysbiosis of gut microbiota may be a promising therapeutic target and biomarker for TBM prevention or treatment.
Experiment 1
Reviewed Marked as Reviewed by Aiyshaaaa on 2023-6-8
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- 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
- Meningeal tuberculosis meningeal tuberculosis,TB meningitis,Meningeal tuberculosis
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy Control (HC)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Tuberculosis Meningitis (TBM)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- The patients who have been diagnosed from Tuberculosis Meningitis (TBM).
- Group 0 sample size Number of subjects in the control (unexposed) group
- 9
- Group 1 sample size Number of subjects in the case (exposed) group
- 9
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- proof of extensive antibiotic therapy for 1+ week in previous 6 months. also, prior treatment of systemic antituberculous therapy for more than 1 week.
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
- Welch's 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
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Aiyshaaaa on 2023-6-8
Source: Supplementary Figure. 1 and 2(A)
Description: The Welch’s t-test was used to analyze phylum and genus level differences in microbiota compositions between pairs of groups: HC and TBM
Abundance in Group 1: increased abundance in Tuberculosis Meningitis (TBM)
| NCBI | Quality Control | Links |
|---|---|---|
| Pseudomonadota | ||
| Escherichia/Shigella sp. |
Revision editor(s): Aiyshaaaa
Signature 2
Reviewed Marked as Reviewed by Aiyshaaaa on 2023-6-8
Source: Supplementary Figure. 1 and 2(A)
Description: The Welch’s t-test was used to analyze phylum and genus level differences in microbiota compositions between pairs of groups: HC and TBM
Abundance in Group 1: decreased abundance in Tuberculosis Meningitis (TBM)
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota | ||
| Bacillota | ||
| Blautia | ||
| Bifidobacterium | ||
| Fusicatenibacter | ||
| Parabacteroides | ||
| Roseburia | ||
| Romboutsia |
Experiment 2
Reviewed Marked as Reviewed by Aiyshaaaa on 2023-6-8
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Pulmonary tuberculosis (PTB)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- The patients who have been diagnosed from Pulmonary tuberculosis (PTB).
- Group 1 sample size Number of subjects in the case (exposed) group
- 13
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- therapy for 1+ week in previous 6 months. also, prior treatment of systemic antituberculous therapy for more than 1 week.
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Aiyshaaaa on 2023-6-8
Source: Supplementary Figure. 1 and 2(B)
Description: Welch’s t-test was used to analyze phylum-level differences in microbiota compositions between pairs of groups: HC and PTB
Abundance in Group 1: increased abundance in Pulmonary tuberculosis (PTB)
| NCBI | Quality Control | Links |
|---|---|---|
| Pseudomonadota | ||
| Bacteroidia | ||
| Bacteroides | ||
| Escherichia/Shigella sp. |
Revision editor(s): Aiyshaaaa
Signature 2
Reviewed Marked as Reviewed by Aiyshaaaa on 2023-6-8
Source: Supplementary Figure. 1 and 2(B)
Description: Welch’s t-test was used to analyze phylum-level differences in microbiota compositions between pairs of groups: HC and PTB
Abundance in Group 1: decreased abundance in Pulmonary tuberculosis (PTB)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Blautia | ||
| Fusicatenibacter | ||
| Dorea | ||
| Romboutsia | ||
| Coprococcus |
Experiment 3
Reviewed Marked as Reviewed by Aiyshaaaa on 2023-6-8
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Pulmonary tuberculosis (PTB)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Tuberculosis Meningitis (TBM)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- The patients who have been diagnosed from Tuberculosis Meningitis (TBM)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 13
- Group 1 sample size Number of subjects in the case (exposed) group
- 9
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- proof of extensive antibiotic therapy for 1+ week in previous 6 months. also, prior treatment of systemic antituberculous therapy for more than 1 week.
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Aiyshaaaa on 2023-6-8
Source: Supplementary Figure. 1 and 2(C)
Description: Welch’s t-test was used to analyze phylum-level differences in microbiota compositions between pairs of groups: TBM and PTB
Abundance in Group 1: increased abundance in Tuberculosis Meningitis (TBM)
| NCBI | Quality Control | Links |
|---|---|---|
| Pseudomonadota | ||
| Escherichia/Shigella sp. |
Revision editor(s): Aiyshaaaa
Signature 2
Reviewed Marked as Reviewed by Aiyshaaaa on 2023-6-8
Source: Supplementary Figure. 1 and 2(C)
Description: Welch’s t-test was used to analyze phylum-level differences in microbiota compositions between pairs of groups: TBM and PTB
Abundance in Group 1: decreased abundance in Tuberculosis Meningitis (TBM)
| NCBI | Quality Control | Links |
|---|---|---|
| Blautia | ||
| Bacteroides | ||
| Actinomycetota | ||
| Bacteroidia | ||
| Bacillota |
Revision editor(s): Aiyshaaaa
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