最近的研究发现肠道菌群对人类健康至关重要，而抗生素应用可能影响肠道菌群的结构和功能，但目前尚缺乏针对持续抗生素使用对人体肠道菌群影响的研究。抗结核治疗要求至少6个月的持续联合抗生素应用，而患者肠道菌群的变化可能改变其胃肠道功能及药物吸收，进而影响治疗结局。本研究利用抗结核治疗6个月疗程的独特契机，通过建立结核病患者队列，观察持续抗生素使用对患者治疗前后肠道菌群构成、相对丰度、生态多样性的影响；进而采用巢式病例对照研究，深入探索肠道菌群变化与患者抗结核药物吸收间的相关性，综合分析肠道菌群变化对结核分枝杆菌消长和耐药基因突变、患者疾病进展和不良反应发生的影响及作用机制，并在上述发现的基础上利用决策树和人工神经网络模型探讨基于改善肠道菌群的抗结核治疗策略。研究将结合肠道菌群基因组学、药代动力学、分子流行病学、微生物学和策略分析等多学科理论和方法，在国家结核病控制项目诊疗规范下完成临床观察和研究。

Recent studies have found that gut microbiota, whose structure and function could be influenced by antibiotic administration, is critical to human health. However, there have been few researches on the effects of persistent antibiotic use on gut microbiota. Anti-tuberculosis treatment requires at least 6 months of continuous combined administration of antibiotics. The consequent changes of gut microbiota may alter gastrointestinal function and drug absorption, thereby affect the outcome of treatment. In this study, taking the unique opportunity of 6 months anti-tuberculosis treatment, we will establish a cohort of tuberculosis patients to observe the composition, relative abundance, ecological diversity of gut microbiota before and after the anti-tuberculosis treatment. Furthermore, a nested case-control study will be performed to explore the correlation between changes of gut microbiota and drug absorption; and to analyze the mechanism of gut microbiota on the activity and gene mutation of Mycobacterium tuberculosis, and the occurrence of adverse events. On the basis of above findings, the decision tree and the artificial neural network model will be applied to optimize the anti-tuberculosis treatment strategy based on the improvement of gut microbiota. This proposed study takes multidisciplinary theories and methods into practice covering genomics, pharmacokinetics, molecular epidemiology, microbiology and strategy analysis. The clinical observation will be carried out following the guidance of China national tuberculosis control program.