Effects of second-line anti-tuberculosis drugs on the intestinal microbiota of patients with rifampicin-resistant tuberculosis

Study information

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study design

case-control

Citation

PMID PubMed identifier for scientific articles.

37187470

DOI Digital object identifier for electronic documents.

10.3389/fcimb.2023.1127916

URI Uniform resource identifier for web resources.

Authors

Wu C, Yi H, Hu Y, Luo D, Tang Z, Wen X, Zhang Y, Tang M, Zhang L, Wu S, Chen M

Journal

Frontiers in cellular and infection microbiology

Year

2023

Keywords:

differential function, differential species, intestinal microbiota, rifampicin-resistant tuberculosis, second-line anti-tuberculosis drugs

OBJECTIVE: To determine the effects of second-line anti-tuberculosis (TB) drugs on the composition and functions of intestinal microbiota in patients with rifampicin-resistant TB (RR-TB). METHODS: In this cross-sectional study, stool samples and relevant clinical information were collected from patients with RR-TB admitted to the Drug-resistant Specialty Department at Hunan Chest Hospital (Hunan Institute For Tuberculosis Control). The composition and functions of intestinal microbiota were analyzed using metagenomic sequencing and bioinformatics methods. RESULTS: Altered structural composition of the intestinal microbiota was found when patients from the control, intensive phase treatment, and continuation phase treatment groups were compared (P<0.05). Second-line anti-TB treatment resulted in a decrease in the relative abundance of species, such as Prevotella copri, compared with control treatment. However, the relative abundance of Escherichia coli, Salmonella enterica, and 11 other conditionally pathogenic species increased significantly in the intensive phase treatment group. Based on differential functional analysis, some metabolism-related functions, such as the biosynthesises of phenylalanine, tyrosine, and tryptophan, were significantly inhibited during second-line anti-TB drug treatment, while other functions, such as phenylalanine metabolism, were significantly promoted during the intensive phase of treatment. CONCLUSION: Second-line anti-TB drug treatment caused changes in the structural composition of the intestinal microbiota in patients with RR-TB. In particular, this treatment induced a significant increase in the relative abundance of 11 conditionally pathogenic species, including Escherichia coli. Functional analysis revealed significantly decreased biosynthesises of phenylalanine, tyrosine, and tryptophan and significantly increased phenylalanine metabolism.

Experiment 1

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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

Drug-resistant tuberculosis , Multidrug-resistant tuberculosis drug resistant tuberculosis,Drug-resistant tuberculosis,drug-resistant tuberculosis,MDR-TB,multidrug-resistant TB,multidrug-resistant tuberculosis,Tuberculosis, Multidrug-Resistant,Multidrug-resistant tuberculosis

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Control (untreated Rifampicin-resistant TB)

Group 1 name Corresponds to the case (exposed) group for case-control studies

Intensive-phase treatment group (G1G2 group)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Rifampicin-resistant tuberculosis patients within 6 months of second-line drugs

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

30

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

60

Lab analysis

Sequencing type

PCR

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

Not specified

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

unchanged

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

unchanged

Chao1 Abundance-based estimator of species richness

unchanged

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

unchanged

Richness Number of species

unchanged

Signature 1

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Source: FIGURE 4; Table 7

Description: Significant differences in relative abundance identified by LEfSe analysis between the three groups (Control, G1G2 and G3G4). At the species level, the untreated group(control) is shown in blue, the intensive treatment group(G1G2) in red and the consolidation treatment group(G3G4) in green. The length of the column represents the influence of significantly different species in relative abundance (LDA scores > 2).

Abundance in Group 1: increased abundance in Intensive-phase treatment group (G1G2 group)

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ProteobacteriaProteobacteria
Citrobacter freundii
Citrobacter koseri
Citrobacter werkmanii
Escherichia coli
Escherichia fergusonii
Klebsiella oxytoca
Klebsiella pneumoniae
Morganella morganii
Salmonella enterica
Shigella sonnei
Proteobacteria bacterium CAG:139
Clostridium spiroformeClostridium spiroforme

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Signature 2

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Source: Figure 4; Table 6

Description: Significant differences in relative abundance identified by LEfSe analysis between the three groups (Control, G1G2 and G3G4). At the species level, the untreated group(control) is shown in blue, the intensive treatment group(G1G2) in red and the consolidation treatment group(G3G4) in green. The length of the column represents the influence of significantly different species in relative abundance (LDA scores > 2).

Abundance in Group 1: decreased abundance in Intensive-phase treatment group (G1G2 group)

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Actinomyces sp. ICM47
Actinomyces sp. S6-Spd3
Actinobaculum sp. oral taxon 183

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Experiment 2

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Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

continuation phase 12–14-month of the treatment (G3G4 group)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

patients who were at the 12–14-month continuation phase of the treatment with second-line anti-TB drugs

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically

unchanged

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

unchanged

Chao1 Abundance-based estimator of species richness

unchanged

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

unchanged

Richness Number of species

unchanged

Signature 1

EditHistoryDelete

Mark reviewed

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Needs review

Curated date: 2025/07/15

Curator: Nuerteye

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Source: Figure 4; Table 8

Description: Significant differences in relative abundance identified by LEfSe analysis between the three groups (Control, G1G2 and G3G4). At the species level, the untreated group(control) is shown in blue, the intensive treatment group(G1G2) in red and the consolidation treatment group(G3G4) in green. The length of the column represents the influence of significantly different species in relative abundance (LDA scores > 2)

Abundance in Group 1: increased abundance in continuation phase 12–14-month of the treatment (G3G4 group)

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Bifidobacterium adolescentis
Butyricicoccus pullicaecorum
Megamonas hypermegale
Kluyvera georgianaKluyvera georgiana

Revision editor(s): Nuerteye

Signature 2

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Source: Figure 4; Table 6

Description: Significant differences in relative abundance identified by LEfSe analysis between the three groups (Control, G1G2 and G3G4). At the species level, the untreated group(control) is shown in blue, the intensive treatment group(G1G2) in red and the consolidation treatment group(G3G4) in green. The length of the column represents the influence of significantly different species in relative abundance (LDA scores > 2).

Abundance in Group 1: decreased abundance in continuation phase 12–14-month of the treatment (G3G4 group)

NCBI	Quality Control	Links
Actinomyces sp. ICM47
Actinomyces sp. S6-Spd3
Actinobaculum sp. oral taxon 183

Revision editor(s): Nuerteye