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. 2021 Apr 15;17(4):e1009377. doi: 10.1371/journal.ppat.1009377

Table 2. Summary of microbiome studies performed on animal models of TB and TB patients, investigating the impact of anti-TB treatment on the host microbiome.

Effects of anti-TB treatment on the host microbiome composition
Location Specimen Host Treatment Change in microbiota composition Effects on the immune system Sequencing technology and data analyisis Ref
Gut Feces LTBI (n = 10), TB (n = 28) TB patients with 1-week anti-TB therapy (TB1, n = 13), TB patients with 2-week anti-TB therapy (T2, n = 10, cured TB patients (TBc, n = 10); healthy individuals (n = 13) INH, RIF, EMB, and PZA Decrease of Ruminococcus and Faecalibacterium. Increased abundance of Bacteroides species and Parabacteroides distasonis in all the treatment groups. n.d. 16S rRNA gene amplicon (Illumina) sequencing; Ribosomal Database Project (RDP) Δ; Mothur v.1.36.1° [258]
Feces LTBI (n = 25), TB treatment (n = 19), cured TB patients (n = 19); individuals without Mtb infection (IGRA-) as controls (n = 50) INH, RIF, EMB, and PZA Enrichment of Erysipelatoclostridium, Fusobacterium, and Prevotella; decrease of Blautia, Lactobacillus, Coprococcus, Ruminococcus, and Bifidobacterium in the TB treatment group. Depletion of Bacteroides and overabundance of Faecalibacterium, Eubacterium, and Ruminococcus in cured TB group: Enterobacter cloacae, Phascolarctobacterium succinatutens, Methanobrevibacter smithii, Bilophila, and Parabacteroides are biomarkers of cured TB patients. n.d. 16S rRNA gene amplicon (Illumina) sequencing; NCBI refseq_rna database with custom scriptsΔ; QIIME°/ Shotgun metagenomic Illumina sequencing; Metaphlan2 (microbial species abundances) and HUMAnN2 (functional pathways) [12]
Feces MDR-TB treatment group (n = 6) and untreated controls (n = 26); MDR-TB recovered group (n = 18) and untreated control (n = 28) MDR-TB treatment Bacteroidetes, Cyanobacteria, and Patescibacteria are biomarkers for the recovered group: decrease of Actinobacteria and Firmicutes; increase of Bacteroidetes in recovered group. n.d. 16S rRNA gene amplicon (Illumina) sequencing; RDP classifier (v 2.2)Δ; Mothur° [13]
Feces 6–10 weeks old C57BL/6 mice (n = 5) infected with Mtb H37Rv; fecal samples collected prior to the treatment as baseline (n = 5) RIF or INH + PYZ Expansion of Bacteroides, Verrucomicrobiaceae, and decrease in Lachnospiraceae in RIF-treated samples; increase of Clostridiaceae in INH/PYZ-treated mice. Expression levels of MHCII and production of TNFα and IL-1β significantly reduced after M. tuberculosis infection. Alveolar macrophages more permissive for intracellular M. tuberculosis replication. 16S rRNA gene amplicon (Illumina) sequencing; Microbiome Analyst web application (community diversity profiling and statistical analysis) [73]
Feces 4–8-week-old C57BL/6J-CD45a(Ly5a) female mice (n = 3–5) infected with M. tuberculosis H37Rv; uninfected age-matched control (n = 3–5) INH, RIF, and PZA + INH and RIF Decrease of genera Acetivibrio, Robinsoniella, Alkaliphilus, Stomatobaculum, Butyricicoccus, Acetanaerobacterium, Tyzzerella, Ruminococcus, and Peptococcus (all belonging to class Clostridia, phylum Firmicutes). n.d. 16S rRNA gene amplicon (Illumina) sequencing; custom reference database built from the NCBI 16S rRNA gene sequence and taxonomy database (version May 2016)Δ; QIIME (v 1.9.1°) [11]
Respiratory tract Sputum samples and throat swab samples New TB group (N-TB, n = 25): patients, cured new TB patients (C-TB, n = 20), recurrent TB group (n = 30), treatment failure group (n = 20); healthy individuals (n = 20) mix of DS-TB and MDR-TB treatments Pseudomonas abundance in TB treatment failure patients or recurrent TB than in new or cured TB patients; Prevotella, Bulleidia, Atopobium, and Treponema decrease in recurrent TB patients than new TB group; increased Corynebacterium abundance in recurrent TB than treatment failure TB. n.d. 16S rRNA gene amplicon (454) pyrosequencing; Greengenes databaseΔ; QIIME (v 1.5.0°) [18]

ΔTaxonomic assignment.

°Operational Taxonomic Units (OTUs) analysis.

DS-TB, drug-susceptible TB; LTBI, latent tuberculosis infection; MDR-TB, multidrug-resistant TB; n.d., not determined; TB, tuberculosis.