Zhang Simin, Xu Zhipeng, Wang Zhan, Fei Xinru, Li Zhongqi, Zhu Limei, Martinez Leonardo, Wang Jianming, Liu Qiao
Department of Epidemiology, Key Laboratory of Public Health Safety and Emergency Prevention and Control Technology of Higher Education Institutions in Jiangsu Province, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, PR China.
Department of Social Medicine and Health Education, National Vaccine Innovation Platform, School of Public Health, Nanjing Medical University, Nanjing, PR China.
BMC Infect Dis. 2025 Apr 1;25(1):453. doi: 10.1186/s12879-025-10800-1.
The treatment of people with tuberculosis necessitates the administration of both broad-spectrum and narrow-spectrum antibiotics for a minimum duration of six months. Prolonged antibiotic therapy may result in dysregulation of the gut microbiota, potentially influencing the onset and progression of tuberculosis. There is a paucity of studies focus on the characteristics of gut microbiota changes at various time points during tuberculosis treatment. This study aims to elucidate the relationship between the composition of gut microbiota and their stage within anti-tuberculosis therapy.
A multi-center, observational prospective cohort study was conducted at four designated hospitals in Jiangsu Province in eastern China. The Gastrointestinal Symptom Rating Scale was employed to evaluate the gastrointestinal discomfort experienced during anti-tuberculosis treatment. Fecal samples were collected at baseline before initiating anti-tuberculosis therapy and at the end of 2 months and 6 months during treatment. Total microbial genomic DNA was extracted and sequenced. Rarefaction curves and alpha diversity indices including observed operational taxonomic units, Chao1 richness and Shannon index were calculated.
From October 2020 to December 2022, a total of 204 people with tuberculosis were diagnosed. Among these, 85 people with tuberculosis provided baseline, 2-month, and 6-month fecal samples. The average age was 41.8 ± 15.193 years, with a gender ratio of 77 males to 8 females. Only 28.2% of the cohort reported being free of gastrointestinal symptoms during anti-tuberculosis treatment. Anti-tuberculosis treatment significantly reduced gut microbiota diversity, with a transient decrease in alpha diversity indices observed after two months. A higher alpha diversity in baseline (Shannon index with mean ± standard deviation (SD) 2.92 ± 0.93 vs. 2.50 ± 0.84, P = 0.0014, inverse Simpson's index with 11.9 ± 8.66 vs. 7.87 ± 6.42, P = 0.0012), compared with people with tuberculosis after 2 months of treatment. No significant differences were identified between 2 months of treatment and at the end of treatment microbiota diversity (Shannon index 2.50 ± 0.84 vs 2.58 ± 0.81, P = 0.55, inverse Simpson's index 7.87 ± 6.42 vs 11.90 ± 8.66, P = 0.43).
Findings from our study show that anti-tuberculosis treatment has profound effects on people with tuberculosis gastrointestinal function and the gut microbiota, particularly during the intensive phase of therapy. After the intensive treatment phase, the gut microbiota has partially recovered, but it is an extremely slow process.
结核病患者的治疗需要使用广谱和窄谱抗生素，最短疗程为六个月。长期抗生素治疗可能导致肠道微生物群失调，从而可能影响结核病的发病和进展。目前针对结核病治疗期间不同时间点肠道微生物群变化特征的研究较少。本研究旨在阐明肠道微生物群组成与其在抗结核治疗阶段之间的关系。
在中国东部江苏省的四家指定医院进行了一项多中心、观察性前瞻性队列研究。采用胃肠道症状评分量表评估抗结核治疗期间经历的胃肠道不适。在开始抗结核治疗前的基线期以及治疗2个月和6个月结束时采集粪便样本。提取总微生物基因组DNA并进行测序。计算稀释曲线和α多样性指数，包括观察到的操作分类单元、Chao1丰富度和香农指数。
2020年10月至2022年12月，共诊断出204例结核病患者。其中，85例结核病患者提供了基线期、2个月和6个月的粪便样本。平均年龄为41.8±15.193岁，男女比例为77例男性对8例女性。队列中只有28.2%的患者报告在抗结核治疗期间没有胃肠道症状。抗结核治疗显著降低了肠道微生物群的多样性，治疗两个月后观察到α多样性指数短暂下降。与治疗2个月后的结核病患者相比，基线期的α多样性更高（香农指数，平均值±标准差[SD]为2.92±0.93对2.50±0.84，P = 0.0014；逆辛普森指数为11.9±8.66对7.87±6.42，P = 0.0012）。治疗2个月时与治疗结束时的微生物群多样性无显著差异（香农指数2.50±0.84对2.58±0.81，P = 0.55；逆辛普森指数7.87±6.42对11.90±8.66，P = 0.43）。
我们的研究结果表明，抗结核治疗对结核病患者的胃肠功能和肠道微生物群有深远影响，尤其是在治疗的强化期。强化治疗阶段后，肠道微生物群有部分恢复，但这是一个极其缓慢的过程。
