Patients infected with Mycobacterium africanum versus Mycobacterium tuberculosis possess distinct intestinal microbiota

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
Namasivayam S, Diarra B, Diabate S, Sarro YDS, Kone A, Kone B, Tolofoudie M, Baya B, Diakite MT, Kodio O, Cohen K, Holl J, Achenbach CJ, Chatterjee S, Murphy RL, Bishai W, Diallo S, Sher A, Maiga M
Journal
PLoS neglected tropical diseases
Year
2020
BACKGROUND: Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB), is composed of eight subspecies. TB in West Africa, in contrast to other geographical regions, is caused by Mycobacterium africanum (MAF) in addition to M. tuberculosis (MTB), with both infections presenting similar symptoms. Nevertheless, MAF is considered to be hypovirulent in comparison with MTB and less likely to progress to active disease. In this study, we asked whether MAF and MTB infected patients possess distinct intestinal microbiomes and characterized how these microbiota communities are affected by anti-tuberculosis therapy (ATT). Additionally, we assessed if the changes in microbiota composition following infection correlate with pathogen induced alterations in host blood-gene expression. METHODS: A longitudinal, clinical study of MAF infected, MTB infected patients assessed at diagnosis and two months after start of ATT, and healthy, endemic controls was conducted to compare compositions of the fecal microbiome as determined by 16S rRNA sequencing. A blood transcriptome analysis was also performed on a subset of subjects in each group by microarray and the results cross-compared with the same individual's microbiota composition. FINDINGS: MAF participants have distinct microbiomes compared with MTB patients, displaying decreased diversity and increases in Enterobacteriaceae with respect to healthy participants not observed in the latter patient group. Interestingly, this observed elevation in Enterobacteriaceae positively correlated with enhanced inflammatory gene expression in peripheral blood and was reversed after initiation of ATT. INTERPRETATION: Our findings indicate that MAF and MTB have distinct associations with the gut microbiome that may be reflective of the differential susceptibility of West Africans to these two co-endemic infections either as biomarkers or as a contributing determinant.

Experiment 1


Needs review

Curated date: 2025/08/02

Curator: Nuerteye

Revision editor(s): Nuerteye

Subjects

Location of subjects
Mali
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 , Feces Expectoration,Sputum,sputum,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
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
Mycobacterium africanum (MAF)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mycobacterium tuberculosis (MTB)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
composed of newly infected active pulmonary tuberculosis patients defined by positive sputum culture
Group 0 sample size Number of subjects in the control (unexposed) group
20
Group 1 sample size Number of subjects in the case (exposed) group
21

Lab analysis

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

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

Signature 1

Needs review

Curated date: 2025/08/02

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 2A-C

Description: Alterations in the composition of the intestinal microbiome of MAF- and MTB-infected patients at the time of diagnosis. a. Relative abundances of the five most prominent phyla are compared between the three groups. b-c. LEfSe analyses were performed to identify differentially abundant families in the two infection groups, MAF and MTB, compared to the healthy participants (b) and between the two infection groups (c). Taxa are filtered for p < 0.05 and linear discriminant analysis (LDA) score > 2.

Abundance in Group 1: increased abundance in Mycobacterium tuberculosis (MTB)

NCBI Quality ControlLinks
Fusobacteriaceae
Clostridiales vadin BB60Clostridiales vadin BB60
Clostridiales Family XIII bacteriumClostridiales Family XIII bacterium
CampylobecteraceaeCampylobecteraceae
Vadin BE97Vadin BE97
Puniceicoccaceae
Heliobacteriaceae

Revision editor(s): Nuerteye

Signature 2

Needs review

Curated date: 2025/08/02

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 2A-C

Description: Alterations in the composition of the intestinal microbiome of MAF- and MTB-infected patients at the time of diagnosis. a. Relative abundances of the five most prominent phyla are compared between the three groups. b-c. LEfSe analyses were performed to identify differentially abundant families in the two infection groups, MAF and MTB, compared to the healthy participants (b) and between the two infection groups (c). Taxa are filtered for p < 0.05 and linear discriminant analysis (LDA) score > 2.

Abundance in Group 1: decreased abundance in Mycobacterium tuberculosis (MTB)

NCBI Quality ControlLinks
Coriobacteriaceae incertae sedis

Revision editor(s): Nuerteye

Experiment 2


Needs review

Curated date: 2025/08/02

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
Healthy controls
Group 0 sample size Number of subjects in the control (unexposed) group
10

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

Signature 1

Needs review

Curated date: 2025/08/02

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 2A-C

Description: Alterations in the composition of the intestinal microbiome of MAF- and MTB-infected patients at the time of diagnosis. a. Relative abundances of the five most prominent phyla are compared between the three groups. b-c. LEfSe analyses were performed to identify differentially abundant families in the two infection groups, MAF and MTB, compared to the healthy participants (b) and between the two infection groups (c). Taxa are filtered for p < 0.05 and linear discriminant analysis (LDA) score > 2.

Abundance in Group 1: decreased abundance in Mycobacterium tuberculosis (MTB)

NCBI Quality ControlLinks
Prevotellaceae
Coriobacteriales incertae sedisCoriobacteriales incertae sedis
Muribaculaceae
CrocinitomicaceaeCrocinitomicaceae
Veillonellaceae
Succinivibrionaceae
Clostridiaceae
Mollicutes RF39Mollicutes RF39

Revision editor(s): Nuerteye

Experiment 3


Needs review

Curated date: 2025/08/02

Curator: Nuerteye

Revision editor(s): Nuerteye

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Mycobacterium africanum (MAF)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
consist of active pulmonary tuberculosis patients defined by positive sputum culture who received anti tuberculosis treatment (ATT) two months after.
Group 1 sample size Number of subjects in the case (exposed) group
20

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/08/02

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 2A-C

Description: Alterations in the composition of the intestinal microbiome of MAF- and MTB-infected patients at the time of diagnosis. a. Relative abundances of the five most prominent phyla are compared between the three groups. b-c. LEfSe analyses were performed to identify differentially abundant families in the two infection groups, MAF and MTB, compared to the healthy participants (b) and between the two infection groups (c). Taxa are filtered for p < 0.05 and linear discriminant analysis (LDA) score > 2.

Abundance in Group 1: increased abundance in Mycobacterium africanum (MAF)

NCBI Quality ControlLinks
Enterobacteriaceae

Revision editor(s): Nuerteye

Experiment 4


Needs review

Curated date: 2025/08/06

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
Mycobacterium africanum plus anti tuberculosis treatment (MAF+HRZE)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mycobacterium tuberculosis plus anti tuberculosis treatment (MTB+HRZE)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
composed of newly infected active pulmonary tuberculosis patients defined by positive sputum culture who received anti tuberculosis treatment for the first two months.
Group 0 sample size Number of subjects in the control (unexposed) group
20
Group 1 sample size Number of subjects in the case (exposed) group
21

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/08/06

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3C

Description: Perturbation in the intestinal microbiome composition due to HRZE treatment in both MAF and MTB infection. c. Pairwise LEfSe comparisons were performed between the three groups to identify differentially abundant families. Taxa are filtered for p <0.05 and LDA score > 2.

Abundance in Group 1: increased abundance in Mycobacterium tuberculosis plus anti tuberculosis treatment (MTB+HRZE)

NCBI Quality ControlLinks
Bifidobacteriaceae
Streptococcaceae
Coriobacteriaceae incertae sedis

Revision editor(s): Nuerteye

Experiment 5


Needs review

Curated date: 2025/08/06

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
Healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mycobacterium africanum plus anti tuberculosis treatment (MAF+HRZE)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
composed of newly infected active pulmonary tuberculosis patients defined by positive sputum culture who received HRZE treatment
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
20

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/08/06

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3C

Description: Perturbation in the intestinal microbiome composition due to HRZE treatment in both MAF and MTB infection. c. Pairwise LEfSe comparisons were performed between the three groups to identify differentially abundant families. Taxa are filtered for p <0.05 and LDA score > 2.

Abundance in Group 1: increased abundance in Mycobacterium africanum plus anti tuberculosis treatment (MAF+HRZE)

NCBI Quality ControlLinks
Peptostreptococcaceae

Revision editor(s): Nuerteye

Signature 2

Needs review

Curated date: 2025/08/06

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3C

Description: Perturbation in the intestinal microbiome composition due to HRZE treatment in both MAF and MTB infection. c. Pairwise LEfSe comparisons were performed between the three groups to identify differentially abundant families. Taxa are filtered for p <0.05 and LDA score > 2.

Abundance in Group 1: decreased abundance in Mycobacterium africanum plus anti tuberculosis treatment (MAF+HRZE)

NCBI Quality ControlLinks
Muribaculaceae
Peptococcaceae
Rikenellaceae
Succinivibrionaceae
unclassified Christensenellaceae
CrocinitomicaceaeCrocinitomicaceae
Actinomycetaceae
Desulfovibrionaceae
Burkholderiaceae
Eggerthellaceae
Akkermansiaceae
Coriobacteriales incertae sedisCoriobacteriales incertae sedis
Clostridiales vadin BB60Clostridiales vadin BB60
Family XIIIFamily XIII
Defluviitaleaceae

Revision editor(s): Nuerteye

Experiment 6


Needs review

Curated date: 2025/08/06

Curator: Nuerteye

Revision editor(s): Nuerteye

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Mycobacterium tuberculosis plus anti tuberculosis treatment (MAF+HRZE))
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
consist of active pulmonary tuberculosis patients defined by positive sputum culture who received anti tuberculosis treatment (ATT) two months after.
Group 1 sample size Number of subjects in the case (exposed) group
21

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/08/06

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3C

Description: Perturbation in the intestinal microbiome composition due to HRZE treatment in both MAF and MTB infection. c. Pairwise LEfSe comparisons were performed between the three groups to identify differentially abundant families. Taxa are filtered for p <0.05 and LDA score > 2.

Abundance in Group 1: decreased abundance in Mycobacterium tuberculosis plus anti tuberculosis treatment (MAF+HRZE))

NCBI Quality ControlLinks
Muribaculaceae
Rikenellaceae
Succinivibrionaceae
unclassified Christensenellaceae
Desulfovibrionaceae
Elusimicrobiaceae
Clostridiaceae 1Clostridiaceae 1
Peptococcaceae
CrocinitomicaceaeCrocinitomicaceae
Marinifilaceae
Family XIIIFamily XIII

Revision editor(s): Nuerteye