The association between the gut microbiome and antituberculosis drug-induced liver injury

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
Pei S, Yang L, Gao H, Liu Y, Lu J, Dai EH, Meng C, Feng F, Wang Y
Journal
Frontiers in pharmacology
Year
2025
Keywords:
anti-TB therapy, drug-induced liver injury, microbiome dysbiosis, probiotics, pulmonary tuberculosis
BACKGROUND: This study aimed to explore the distinct characteristics of the gut microbiota in tuberculosis (TB) patients who experienced liver injury following anti-TB treatment compared with those who did not. METHOD: We employed a nested case-control study design, recruiting newly diagnosed pulmonary TB patients at Tangshan Infectious Disease Hospital. Participants were categorized into the Antituberculosis Drug-Induced Liver Injury (ADLI) group and the Non-ADLI group based on the occurrence of liver injury after treatment. Both groups received identical anti-TB regimens. Stool samples were collected from patients who developed liver injury within 2-3 weeks of starting treatment, alongside matched controls during the same timeframe. The samples underwent 16S rDNA sequencing, and clinical data and blood samples were also collected for further analysis. At the same time, we constructed mouse models to explore the effects of different anti-tuberculosis drugs on gut microbiota. RESULTS: Following anti-TB treatment, we observed a decrease in microbial diversity and significant structural changes in the gut microbiota of TB patients (P < 0.05). At T1, the Non_ADLI_T1 group presented relatively high levels of Phascolarctobacterium, Anaerofustis and Mailhella. In contrast, the ADLI_ T1 group presented elevated levels of Bacteroides, Veillonella, Clavibacter, Corynebacterium, Anaerococcus, Gardnerella, Peptostreptococcus and Lautropia. At T2, the ADLI_T2 group presented increased levels of Enterococcus, Faecalibacterium, unclassified_f__Burkholderiaceae, Cardiobacterium, Ruminococcus_gnavus_group and Tyzzerella_4 than did the Non_ADLI_T2 group. Additionally, the ADLI_T2 group presented decreased levels of Prevotella_9, Akkermansia, Erysipelotrichaceae_UCG-003, Rubrobacter and norank_f__Desulfovibrionaceae than did the Non_ADLI_T2 group. In animal experiments, similar changes to those in the human population were observed in the mouse model compared to the control group. Any single anti-tuberculosis drug or two-drug combination or three-drug combination can cause dysbiosis of the mouse gut microbiota. The signature genera between groups are different and related to the type of anti-tuberculosis drug. CONCLUSION: Anti-tuberculosis treatment induces dysbiosis in the gut microbiota of TB patients. Notably, there are significant differences in microbiota characteristics between TB patients with and without liver injury at both onset and during treatment. There are some differences in the characteristics of bacterial flora in liver injury caused by different drugs.

Experiment 1


Needs review

Curated date: 2025/07/22

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
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
Non- ADLI controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Antituberculosis Drug-Induced Liver Injury (ADLI) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
newly diagnosed patients with tuberculosis according to the WS 288–2017 Diagnosis of Pulmonary Tuberculosis standard
Group 0 sample size Number of subjects in the control (unexposed) group
100
Group 1 sample size Number of subjects in the case (exposed) group
100
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Patients had not used antibiotics in the past month prior to the study

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
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
3

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/07/23

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3A

Description: Longitudinal comparison of bacterial genera with and without liver injury in patients with pulmonary tuberculosis. Characteristics of genus changes from T1 to T2 in Non_ADLI group

Abundance in Group 1: increased abundance in Antituberculosis Drug-Induced Liver Injury (ADLI) group

NCBI Quality ControlLinks
Akkermansia
Faecalibacterium
Lachnoclostridium
Subdoligranulum
Prevotella_9Prevotella_9
Collinsella
Blautia
Ruminococcus 2Ruminococcus 2
Ruminococcus tarquesRuminococcus tarques
Alloprevotella
Ruminiclostridium
Holdemanella
Mahella
Alistipes
Roseburia
Ruminococcaceae UCG 011Ruminococcaceae UCG 011
Sanguibacteroides
Muribaculaceae

Revision editor(s): Nuerteye

Signature 2

Needs review

Curated date: 2025/07/23

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3A

Description: Longitudinal comparison of bacterial genera with and without liver injury in patients with pulmonary tuberculosis. Characteristics of genus changes from T1 to T2 in Non_ADLI group

Abundance in Group 1: decreased abundance in Antituberculosis Drug-Induced Liver Injury (ADLI) group

NCBI Quality ControlLinks
Escherichia-ShigellaEscherichia-Shigella
Klebsiella
Veillonella
Enterococcus
Citrobacter
unclassified Enterobacteriaceae

Revision editor(s): Nuerteye

Experiment 2


Needs review

Curated date: 2025/07/23

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
Antituberculosis Drug-Induced Liver Injury (ADLI_T1) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Antituberculosis Drug-Induced Liver Injury (ADLI_T2) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
ADLI_T2, specimens from patients who developed liver injury following anti-TB treatment.

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/07/23

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3B

Description: Longitudinal comparison of bacterial genera with and without liver injury in patients with pulmonary tuberculosis. ADLI_T1—liver-damaged group at T1; ADLI_T2—liver-damaged group at T2. Characteristics of genus changes from T1 to T2 in ADLI group.

Abundance in Group 1: increased abundance in Antituberculosis Drug-Induced Liver Injury (ADLI_T2) group

NCBI Quality ControlLinks
Agathobacter
Akkermansia
Alistipes
Subdoligranulum
Prevotella_9Prevotella_9
Faecalibacterium
Holdemanella
Alloprevotella
Parvimonas
Ruminiclostridium 6Ruminiclostridium 6
Blautia
Ruminococcus 1Ruminococcus 1
RuminococcaceaeRuminococcaceae
Ruminococcus torquesRuminococcus torques
Roseburia
Faecalibacterium sp. UBA1819
Erysipelotrichaceae UCG-003Erysipelotrichaceae UCG-003
Clostridiales vadinBB60Clostridiales vadinBB60
Eubacterium coprostanoligenes
Lachnospiraceae bacterium NK4A136
Ruminococcaceace UCG-002Ruminococcaceace UCG-002
Ruminococcaceae UCG-014Ruminococcaceae UCG-014
Muribaculaceae
Bacteria
unclassified Ruminococcaceaeunclassified Ruminococcaceae

Revision editor(s): Nuerteye

Signature 2

Needs review

Curated date: 2025/07/23

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 3B

Description: Longitudinal comparison of bacterial genera with and without liver injury in patients with pulmonary tuberculosis. ADLI_T1—liver-damaged group at T1; ADLI_T2—liver-damaged group at T2. Characteristics of genus changes from T1 to T2 in ADLI group.

Abundance in Group 1: decreased abundance in Antituberculosis Drug-Induced Liver Injury (ADLI_T2) group

NCBI Quality ControlLinks
Anaerostipes
Citrobacter
Coprobacter
Escherichia/Shigella sp.
Klebsiella
Paraprevotella
unclassified Enterobacteriaceae
Ruminococcus_2Ruminococcus_2
ErysipelatoclostridiumErysipelatoclostridium

Revision editor(s): Nuerteye

Experiment 3


Needs review

Curated date: 2025/07/23

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
Non-Antituberculosis Drug-Induced Liver Injury (Non_ADLI_T1) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Antituberculosis Drug-Induced Liver Injury (ADLI_T1) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
ADLI_T1, specimens collected from patients prior to the initiation of anti-TB treatment upon admission.

Lab analysis

Statistical Analysis

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/07/23

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 4A

Description: Comparative analysis of bacterial genera at the same time point between pulmonary tuberculosis patients with liver injury and those without liver injury. Non_ADLI_T1—nonsevere-damaged group at T1; ADLI_T1—liver-damaged group at T1. Characteristics of genus differences between Non_ADLI group and ADLI group at T1.

Abundance in Group 1: increased abundance in Antituberculosis Drug-Induced Liver Injury (ADLI_T1) group

NCBI Quality ControlLinks
Bacteroides
Veillonella
Clavibacter
Corynebacterium
Anaerococcus
Gardnerella
Peptostreptococcus
Lautropia

Revision editor(s): Nuerteye

Signature 2

Needs review

Curated date: 2025/07/23

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 4A

Description: Comparative analysis of bacterial genera at the same time point between pulmonary tuberculosis patients with liver injury and those without liver injury. Non_ADLI_T1—nonsevere-damaged group at T1; ADLI_T1—liver-damaged group at T1. Characteristics of genus differences between Non_ADLI group and ADLI group at T1.

Abundance in Group 1: decreased abundance in Antituberculosis Drug-Induced Liver Injury (ADLI_T1) group

NCBI Quality ControlLinks
Phascolarctobacterium
Anaerofustis
Mailhella

Revision editor(s): Nuerteye

Experiment 4


Needs review

Curated date: 2025/07/23

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
Non-Antituberculosis Drug-Induced Liver Injury (Non-ADLI_T2) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Antituberculosis Drug-Induced Liver Injury (ADLI_T2) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
ADLI_T2, specimens from patients who developed liver injury following anti-TB treatment.

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/07/23

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 4B

Description: Comparative analysis of bacterial genera at the same time point between pulmonary tuberculosis patients with liver injury and those without liver injury. Non_ADLI_T2—nonseiver-damaged group at T2; ADLI_T2—liver-damaged group at T2. Characteristics of genus differences between Non_ADLI group and ADLI group at T2.

Abundance in Group 1: increased abundance in Antituberculosis Drug-Induced Liver Injury (ADLI_T2) group

NCBI Quality ControlLinks
Cardiobacterium
Enterococcus
Faecalibacterium
unclassified Burkholderiaceae
Ruminococcus gnavusRuminococcus gnavus
Tyzzerella sp.

Revision editor(s): Nuerteye

Signature 2

Needs review

Curated date: 2025/07/23

Curator: Nuerteye

Revision editor(s): Nuerteye

Source: Figure 4B

Description: Comparative analysis of bacterial genera at the same time point between pulmonary tuberculosis patients with liver injury and those without liver injury. Non_ADLI_T2—nonseiver-damaged group at T2; ADLI_T2—liver-damaged group at T2. Characteristics of genus differences between Non_ADLI group and ADLI group at T2.

Abundance in Group 1: decreased abundance in Antituberculosis Drug-Induced Liver Injury (ADLI_T2) group

NCBI Quality ControlLinks
Prevotella_9Prevotella_9
Akkermansia
Erysipelotrichaceae UCG-003Erysipelotrichaceae UCG-003
Rubrobacter
unclassified Desulfovibrionaceae

Revision editor(s): Nuerteye