Sputum microbiota profiles of treatment-naïve TB patients in Uganda before and during first-line therapy

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
Kateete DP, Mbabazi MM, Nakazzi F, Katabazi FA, Kigozi E, Ssengooba W, Nakiyingi L, Namiiro S, Okwera A, Joloba ML, Muwonge A
Journal
Scientific reports
Year
2021
Information on microbiota dynamics in pulmonary tuberculosis (TB) in Africa is scarce. Here, we sequenced sputa from 120 treatment-naïve TB patients in Uganda, and investigated changes in microbiota of 30 patients with treatment-response follow-up samples. Overall, HIV-status and anti-TB treatment were associated with microbial structural and abundance changes. The predominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria and Actinobacteria, accounting for nearly 95% of the sputum microbiota composition; the predominant genera across time were Prevotella, Streptococcus, Veillonella, Haemophilus, Neisseria, Alloprevotella, Porphyromonas, Fusobacterium, Gemella, and Rothia. Treatment-response follow-up at month 2 was characterized by a reduction in abundance of Mycobacterium and Fretibacterium, and an increase in Ruminococcus and Peptococcus; month 5 was characterized by a reduction in Tannerella and Fusobacterium, and an increase in members of the family Neisseriaceae. The microbiota core comprised of 44 genera that were stable during treatment. Hierarchical clustering of this core's abundance distinctly separated baseline (month 0) samples from treatment follow-up samples (months 2/5). We also observed a reduction in microbial diversity with 9.1% (CI 6-14%) of the structural variation attributed to HIV-status and anti-TB treatment. Our findings show discernible microbiota signals associated with treatment with potential to inform anti-TB treatment response monitoring.

Experiment 1


Needs review

Curated date: 2025/06/11

Curator: Nuerteye

Revision editor(s): Nuerteye

Subjects

Location of subjects
Uganda
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
Sputum Expectoration,Sputum,sputum
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Pulmonary tuberculosis lung TB,lung tuberculosis,pulmonary TB,pulmonary tuberculosis,Tuberculosis, Pulmonary,Pulmonary tuberculosis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Baseline (pre-treatment)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Month 2 and Month 5 follow-up
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Sputum collected at 2 months (end of intensive phase) and 5 months (end of therapy) of first-line anti-TB regimen.
Group 0 sample size Number of subjects in the control (unexposed) group
106
Group 1 sample size Number of subjects in the case (exposed) group
44
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
All were treatment-naïve at baseline; no anti-TB drugs prior to sampling; other antibiotic history not exclusionary.

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
ANOVA
Kruskall-Wallis
Mixed-Effects Regression
PERMANOVA
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)?
Yes
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "HIV status" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.HIV status, Confounders controlled for: "BMI" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.BMI, Confounders controlled for: "gender" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.gender

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on 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: 2025/06/11

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 2

Description: Fig. 2 shows relative-abundance shifts of major genera across baseline, Month 2 and Month 5.

Abundance in Group 1: increased abundance in Month 2 and Month 5 follow-up

NCBI Quality ControlLinks
Ruminococcus bromii
Peptococcus niger
Neisseria subflava

Revision editor(s): Nuerteye

Signature 2

Needs review

Curated date: 2025/06/11

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 2

Description: Fig. 2 shows relative-abundance shifts of major genera across baseline, Month 2 and Month 5.

Abundance in Group 1: decreased abundance in Month 2 and Month 5 follow-up

NCBI Quality ControlLinks
Mycobacterium tuberculosis
Fretibacterium fastidiosum
Tannerella forsythia
Fusobacterium nucleatum

Revision editor(s): Nuerteye

Experiment 2


Needs review

Curated date: 2025/06/11

Curator: Nuerteye

Revision editor(s): Nuerteye

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Sputum collected at 2 months (end of intensive phase) and 5 months (end of therapy) of first-line anti-TB regimen

Lab analysis

Statistical Analysis

Alpha Diversity

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