Pei Shengfei, Yang Li, Gao Huixia, Liu Yuzhen, Lu Jianhua, Dai Er Hei, Meng Chunyan, Feng Fumin, Wang Yuling
Hebei Coordinated Innovation Center of Occupational Health and Safety, School of Public Health, North China University of Science of Technology, Tangshan, China.
Hebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Shijiazhuang, China.
Front Pharmacol. 2025 Mar 10;16:1512815. doi: 10.3389/fphar.2025.1512815. eCollection 2025.
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.
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.
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 , and . In contrast, the ADLI_ T1 group presented elevated levels of , , , , , , and . At T2, the ADLI_T2 group presented increased levels of , , , , and than did the Non_ADLI_T2 group. Additionally, the ADLI_T2 group presented decreased levels of , , and 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.
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.
本研究旨在探讨抗结核治疗后出现肝损伤的结核病（TB）患者与未出现肝损伤的患者肠道微生物群的不同特征。
我们采用巢式病例对照研究设计，在唐山市传染病医院招募新诊断的肺结核患者。根据治疗后肝损伤的发生情况，将参与者分为抗结核药物性肝损伤（ADLI）组和非ADLI组。两组接受相同的抗结核治疗方案。在开始治疗后2 - 3周内，从出现肝损伤的患者以及同一时间范围内匹配的对照者中采集粪便样本。对样本进行16S rDNA测序，并收集临床数据和血液样本进行进一步分析。同时，我们构建小鼠模型以探讨不同抗结核药物对肠道微生物群的影响。
抗结核治疗后，我们观察到结核病患者肠道微生物群的多样性降低且结构发生显著变化（P < 0.05）。在T1时，非ADLI_T1组呈现相对较高水平的 、 和 。相比之下，ADLI_T1组呈现升高水平的 、 、 、 、 、 、 和 。在T2时，ADLI_T2组呈现比非ADLI_T2组更高水平的 、 、 、 、 和 。此外，ADLI_T2组呈现比非ADLI_T2组更低水平的 、 、 和 。在动物实验中，与对照组相比，在小鼠模型中观察到与人类群体中相似的变化。任何单一抗结核药物或两药联合或三药联合均可导致小鼠肠道微生物群失调。组间标志性菌属不同且与抗结核药物类型有关。
抗结核治疗可导致结核病患者肠道微生物群失调。值得注意的是，在发病时和治疗期间，有肝损伤和无肝损伤的结核病患者的微生物群特征存在显著差异。不同药物引起的肝损伤中细菌菌群特征存在一些差异。
