Gut microbiome, T cell subsets, and cytokine analysis identify differential biomarkers in tuberculosis

Study information

Needs review

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

38650928

DOI Digital object identifier for electronic documents.

10.3389/fimmu.2024.1323723

URI Uniform resource identifier for web resources.

Authors

Chai Y, Liu X, Bai G, Zhou N, Liu D, Zhang X, Li M, Li K, Lei H

Journal

Frontiers in immunology

Year

2024

Keywords:

T cell subsets, biomarkers, cytokines, gut microbiome, tuberculosis

INTRODUCTION: The gut microbiota, T cell subsets, and cytokines participate in tuberculosis (TB) pathogenesis. To date, the mechanisms by which these factors interactively promote TB development at different time points remain largely unclear. In the context of this study, We looked into the microorganisms in the digestive tract, T cell types, and cytokines related to tuberculosis. METHODS: According to QIIME2, we analyzed 16SrDNA sequencing of the gut microbiome on the Illumina MiSeq. Enzyme-linked immunosorbent assay was used to measure the concentrations of cytokines. RESULTS: We showed the presence of 26 identifiable differential microbiomes in the gut and 44 metabolic pathways between healthy controls and the different time points in the development of TB in patients. Five bacterial genera (Bacteroides, Bifidobacterium, Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4/CD8, whereas three bacterial taxa (Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4. Three bacterial taxa (Faecalibacterium, Ruminococcus, and Dorea) were most closely associated with IL-4. Ruminococcus was most closely associated with IL-2 and IL-10. CONCLUSION: Diverse microorganisms, subsets of T cells, and cytokines, exhibiting varying relative abundances and structural compositions, were observed in both healthy controls and patients throughout distinct phases of tuberculosis. Gaining insight into the function of the gut microbiome, T cell subsets, and cytokines may help modulate therapeutic strategies for TB.

Experiment 1

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Curated date: 2025/07/29

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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: Tuberculosis active tuberculosis,Kochs disease,TB,tuberculosis,tuberculosis disease,Tuberculosis

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Combination of TB patients (cz group) and retreated patients (fz group)

Group 1 name Corresponds to the case (exposed) group for case-control studies: healthy controls (jk group)

Group 0 sample size Number of subjects in the control (unexposed) group: 60

Group 1 sample size Number of subjects in the case (exposed) group: 30

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): never used antituberculosis drugs or were treated with antituberculosis drugs for the first time for less than 1 month

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

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

Alpha Diversity

Pielou Quantifies how equal the community is numerically: increased

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

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: increased

Richness Number of species: increased

Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample: increased

Signature 1

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Curated date: 2025/07/29

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Source: Figure 3A and 3B

Description: Identification of different genera as biomarkers by relative abundance. (A) The column length signifies the impact of distinct species in terms of relative abundance (linear discriminant analysis scores > 4). (B) The clado-gram displays the species that are markedly distinct. Each circle symbolizes the phylogenetic progression from phylum to genus, encompassing both the interior and exterior. The size of each circle is linked to the number of taxa present, and the biomarker is in agreement with the group indicated by the color.

Abundance in Group 1: increased abundance in healthy controls (jk group)

NCBI	Quality Control	Links
Coprococcus
Roseburia
Peptostreptococcaceae
Clostridiaceae
Dorea
Rikenellaceae
Lachnospiraceae
Clostridium
Collinsella
Alistipes
AdlecreutziaAdlecreutzia
TenericutesTenericutes
Enterococcaceae bacterium RF39
Mollicutes
Sutterella
Pediococcus
unclassified Christensenellaceae
Lachnospira
Lachnobacterium
Barnesiella
MogibacteriaceaeMogibacteriaceae
Gemm 3Gemm 3
Butyricimonas

Revision editor(s): Nuerteye

Experiment 2

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Combination of retreated patients (fz group) and healthy controls (jk group)

Group 1 name Corresponds to the case (exposed) group for case-control studies: TB patients (cz group)

Lab analysis

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Statistical Analysis

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 4

Alpha Diversity

Pielou Quantifies how equal the community is numerically: decreased

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Chao1 Abundance-based estimator of species richness: decreased

Simpson Estimator of species richness and species evenness: more weight on species evenness: decreased

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: decreased

Richness Number of species: decreased

Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample: decreased

Signature 1

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2025/07/29

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3A and 3B

Description: Identification of different genera as biomarkers by relative abundance. (A) The column length signifies the impact of distinct species in terms of relative abundance (linear discriminant analysis scores > 4). (B) The clado-gram displays the species that are markedly distinct. Each circle symbolizes the phylogenetic progression from phylum to genus, encompassing both the interior and exterior. The size of each circle is linked to the number of taxa present, and the biomarker is in agreement with the group indicated by the color.

Abundance in Group 1: increased abundance in TB patients (cz group)

NCBI	Quality Control	Links
Lachnospiraceae
Gemmiger
Eubacterium
Actinomycetaceae
Actinomyces
TM7TM7
TM7 3TM7 3
Bulleidia
Comamonas
Coxiellaceae
Rickettsiella sp.
Legionellales
Gaiella

Revision editor(s): Nuerteye

Experiment 3

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Mark reviewed

Your review change was submittedDuplicate this Experiment Add a new Signature

Needs review

Curated date: 2025/07/29

Curator: Nuerteye

Revision editor(s): Nuerteye

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Combination of TB patients (cz group) and healthy controls (jk group)

Group 1 name Corresponds to the case (exposed) group for case-control studies: retreated patients (fz group)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: patients with recurrent TB in the fz group

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically: decreased

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Chao1 Abundance-based estimator of species richness: decreased

Simpson Estimator of species richness and species evenness: more weight on species evenness: decreased

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: decreased

Richness Number of species: decreased

Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample: decreased

Signature 1

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2025/07/29

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3A and 3B

Description: Identification of different genera as biomarkers by relative abundance. (A) The column length signifies the impact of distinct species in terms of relative abundance (linear discriminant analysis scores > 4). (B) The clado-gram displays the species that are markedly distinct. Each circle symbolizes the phylogenetic progression from phylum to genus, encompassing both the interior and exterior. The size of each circle is linked to the number of taxa present, and the biomarker is in agreement with the group indicated by the color.

Abundance in Group 1: increased abundance in retreated patients (fz group)

NCBI	Quality Control	Links
ProteobacteriaProteobacteria
Gammaproteobacteria
Enterobacteriaceae
Enterobacterales
Erysipelotrichaceae
Coprobacillus
Acidaminococcus

Revision editor(s): Nuerteye