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

BackgroundThis 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.MethodWe employed a nested case-control study design, recruiting newly diagnosed pulmonary T...

Full description

Saved in:
Bibliographic Details
Main Authors: Shengfei Pei, Li Yang, Huixia Gao, Yuzhen Liu, Jianhua Lu, Er hei Dai, Chunyan Meng, Fumin Feng, Yuling Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1512815/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850250378494345216
author Shengfei Pei
Li Yang
Huixia Gao
Yuzhen Liu
Jianhua Lu
Er hei Dai
Chunyan Meng
Fumin Feng
Yuling Wang
author_facet Shengfei Pei
Li Yang
Huixia Gao
Yuzhen Liu
Jianhua Lu
Er hei Dai
Chunyan Meng
Fumin Feng
Yuling Wang
author_sort Shengfei Pei
collection DOAJ
description BackgroundThis 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.MethodWe 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.ResultsFollowing 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.ConclusionAnti-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.
format Article
id doaj-art-c44d6919a19e421a8225d280df447d8a
institution OA Journals
issn 1663-9812
language English
publishDate 2025-03-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
spelling doaj-art-c44d6919a19e421a8225d280df447d8a2025-08-20T01:58:12ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15128151512815The association between the gut microbiome and antituberculosis drug-induced liver injuryShengfei Pei0Li Yang1Huixia Gao2Yuzhen Liu3Jianhua Lu4Er hei Dai5Chunyan Meng6Fumin Feng7Yuling Wang8Hebei Coordinated Innovation Center of Occupational Health and Safety, School of Public Health, North China University of Science of Technology, Tangshan, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital ofShijiazhuang, Shijiazhuang, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital ofShijiazhuang, Shijiazhuang, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital ofShijiazhuang, Shijiazhuang, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital ofShijiazhuang, Shijiazhuang, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital ofShijiazhuang, Shijiazhuang, ChinaHebei Coordinated Innovation Center of Occupational Health and Safety, School of Public Health, North China University of Science of Technology, Tangshan, ChinaHebei Coordinated Innovation Center of Occupational Health and Safety, School of Public Health, North China University of Science of Technology, Tangshan, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital ofShijiazhuang, Shijiazhuang, ChinaBackgroundThis 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.MethodWe 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.ResultsFollowing 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.ConclusionAnti-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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1512815/fullpulmonary tuberculosisanti-TB therapymicrobiome dysbiosisprobioticsdrug-induced liver injury
spellingShingle Shengfei Pei
Li Yang
Huixia Gao
Yuzhen Liu
Jianhua Lu
Er hei Dai
Chunyan Meng
Fumin Feng
Yuling Wang
The association between the gut microbiome and antituberculosis drug-induced liver injury
Frontiers in Pharmacology
pulmonary tuberculosis
anti-TB therapy
microbiome dysbiosis
probiotics
drug-induced liver injury
title The association between the gut microbiome and antituberculosis drug-induced liver injury
title_full The association between the gut microbiome and antituberculosis drug-induced liver injury
title_fullStr The association between the gut microbiome and antituberculosis drug-induced liver injury
title_full_unstemmed The association between the gut microbiome and antituberculosis drug-induced liver injury
title_short The association between the gut microbiome and antituberculosis drug-induced liver injury
title_sort association between the gut microbiome and antituberculosis drug induced liver injury
topic pulmonary tuberculosis
anti-TB therapy
microbiome dysbiosis
probiotics
drug-induced liver injury
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1512815/full
work_keys_str_mv AT shengfeipei theassociationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT liyang theassociationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT huixiagao theassociationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT yuzhenliu theassociationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT jianhualu theassociationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT erheidai theassociationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT chunyanmeng theassociationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT fuminfeng theassociationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT yulingwang theassociationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT shengfeipei associationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT liyang associationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT huixiagao associationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT yuzhenliu associationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT jianhualu associationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT erheidai associationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT chunyanmeng associationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT fuminfeng associationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury
AT yulingwang associationbetweenthegutmicrobiomeandantituberculosisdruginducedliverinjury