The potential mechanism of the progression from latent to active tuberculosis based on the intestinal microbiota alterations

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
Luo D, Shi CY, Wei NS, Yang BY, Qin K, Liu G, Dong BQ, Qin YX, Qin XL, Chen SY, Guo XJ, Gan L, Xu RL, Li H, Li J
Journal
Tuberculosis (Edinburgh, Scotland)
Year
2023
Keywords:
16S rDNA sequencing, Intestinal microbiota, LTBI, Tuberculosis
INTRODUCTION: Tuberculosis (TB) poses a serious challenge to global health systems. The altered intestinal microbiota is associated with the pathogenesis of TB, but the exact links remain unclear. METHODS: 16 S rDNA sequencing was performed to comprehensively detect the changes in the intestinal microbiota of feces from active TB (ATB), latent TB infection (LTBI) and healthy controls (HC). RESULTS: The rarefaction curves demonstrated the sequencing results' validity. The alpha diversity was lowest in ATB, while highest in HC. Boxplot of beta diversity showed significant differences in every two groups. LDA Effect Size (LEfSe) Analysis revealed differences in probiotic bacteria like Romboutsia, Bifidobacterium and Lactobacillus in LTBI, and pro-inflammatory bacteria like R. gnavus, Streptococcus and Erysipelatoclostridium in ATB, corresponding to the cluster analysis. PICRUST2 analysis revealed the pentose phosphate pathway was active in ATB and LTBI (more active in ATB). The differences between the groups are statistically significant at the P<0.05 level. CONCLUSION: Our study indicated that from LTBI to ATB, some intestinal microbiota inhibit the synthesis of interferon (INF)-γ and interleukin (IL)-17, promoting the survival and spread of Mycobacterium tuberculosis (M. tb). In addition, the metabolites secreted by intestinal microbiota and dysbiosis in intestine also have an effect on the development of LTBI to ATB.

Experiment 1


Needs review

Curated date: 2025/07/29

Curator: Nuerteye

Revision editor(s): Nuerteye

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 active tuberculosis (ATB) and latent tuberculosis infection (LTBI)
Group 1 name Corresponds to the case (exposed) group for case-control studies
healthy controls
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
All cases had no previous history of tuberculosis
Group 0 sample size Number of subjects in the control (unexposed) group
42
Group 1 sample size Number of subjects in the case (exposed) group
11
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
previous history of treatment using antibiotics

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V5
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
4

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: 2025/07/29

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 5A-B

Description: The enrichment deviation diagram of three groups based on LEfSe analysis (selection criteria: P<0.05; LDA score ≥ 4). Histogram of LDA value of intestinal microbiota in three groups. The column represents LDA Score, and the colors represent the microbiota in three groups, respectively. LEfSe cladogram of LEfSe analysis.

Abundance in Group 1: increased abundance in healthy controls

NCBI Quality ControlLinks
Prevotellaceae
Prevotella
Holdemanella
Prevotella copriPrevotella copri
Negativicutes
Veillonellales selenomonadalesVeillonellales selenomonadales

Revision editor(s): Nuerteye

Experiment 2


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 healthy controls (HC) and latent tuberculosis infection (LTBI)
Group 1 name Corresponds to the case (exposed) group for case-control studies
active tuberculosis (ATB)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patents with ATB enrolled according to Technical Guidelines for Tuberculosis Prevention and Control in China [20] and all cases had no previous history of TB.
Group 0 sample size Number of subjects in the control (unexposed) group
24
Group 1 sample size Number of subjects in the case (exposed) group
29

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
Not specified

Alpha Diversity

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
Richness Number of species
decreased

Signature 1

Needs review

Curated date: 2025/07/29

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 5A-B

Description: The enrichment deviation diagram of three groups based on LEfSe analysis (selection criteria: P<0.05; LDA score ≥ 4). Histogram of LDA value of intestinal microbiota in three groups. The column represents LDA Score, and the colors represent the microbiota in three groups, respectively. LEfSe cladogram of LEfSe analysis.

Abundance in Group 1: increased abundance in active tuberculosis (ATB)

NCBI Quality ControlLinks
Bacilli
Lactobacillales
Ruminococcus gnavusRuminococcus gnavus
Streptococcaceae
Streptococcus
ErysipelatoclostridiaceaeErysipelatoclostridiaceae
Blautia caecimurisBlautia caecimuris
ErysipelatoclostridiumErysipelatoclostridium
Enterobacterales
Enterobacteriaceae

Revision editor(s): Nuerteye

Experiment 3


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 healthy controls (HC) and active tuberculosis (ATB)
Group 1 name Corresponds to the case (exposed) group for case-control studies
latent tuberculosis infection (LTBI)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Positive IGRAs and/or TST (nodule ≥15 mm, blister or necrosis), but had no clinical symptoms of TB.
Group 0 sample size Number of subjects in the control (unexposed) group
40
Group 1 sample size Number of subjects in the case (exposed) group
13

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

Signature 1

Needs review

Curated date: 2025/07/29

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 5A-B

Description: The enrichment deviation diagram of three groups based on LEfSe analysis (selection criteria: P<0.05; LDA score ≥ 4). Histogram of LDA value of intestinal microbiota in three groups. The column represents LDA Score, and the colors represent the microbiota in three groups, respectively. LEfSe cladogram of LEfSe analysis.

Abundance in Group 1: increased abundance in latent tuberculosis infection (LTBI)

NCBI Quality ControlLinks
Bifidobacterium
Bifidobacteriales
Bifidobacteriaceae
Lactobacillus
unclassified Lactobacillaceae
Romboutsia

Revision editor(s): Nuerteye