Table 5_Metabolic and immune consequences of antibiotic related microbiome alterations during first-line tuberculosis treatment in Bamako, Mali.xlsx

BackgroundIndividuals with a history of tuberculosis (TB) treatment are at a higher risk of experiencing a recurrent episode of the disease. Previous cross-sectional studies identified a connection between dysbiosis (alterations) in the gut microbiota composition and the administration of first-line TB antibiotics. However, these studies have not successfully elucidated this dysbiosis’s resulting metabolic and immune consequences.
MethodsIn a longitudinal assessment, we studied the antituberculosis drug-related changes in the gut microbiota’s composition and the resulting functional consequences. Sputum for TB culture, peripheral blood for metabolomics and cytokines analysis, and stool for shotgun metagenomics were collected from TB participants at Month-0, Month-2, Month-6 of treatment, and 9 Months after treatment (Month-15). Healthy controls were sampled at Month-0 and Month-6.
FindingsWe found notable differences in gut microbiota between individuals with TB and healthy controls. While gut microbiota tended to resemble healthy controls at the end of TB treatment, significant differences for many taxa persisted up to Month-15. Concurrently, disturbances in plasma metabolites, including tryptophan, tricarboxylic acids, and cytokine levels were observed. Certain fatty acids associated with inflammation pathways negatively correlated with the abundance of several taxa.
ConclusionWe observed alterations in the gut microbiota composition and function during treatment and at Month-15. Numerous changes in bacterial taxa abundances and inflammation-linked metabolites did not reverse at Month-15. This study suggests potential influences of anti-TB drugs and the gut microbiome on the disease outcome, response to treatment, and resistance to future TB infections.

背景：有结核病（tuberculosis, TB）治疗史的个体，疾病复发风险显著升高。既往横断面研究已发现肠道菌群失调（dysbiosis）与一线抗结核抗生素使用之间存在关联，但此类研究尚未阐明该菌群失调所引发的代谢与免疫后果。
方法：本研究通过纵向研究设计，考察抗结核药物对肠道菌群组成的影响及其潜在功能效应。研究对象为结核病患者，分别在治疗第0个月、第2个月、第6个月以及治疗结束后9个月（即第15个月）采集样本：包括用于结核分枝杆菌培养的痰液、用于代谢组学与细胞因子分析的外周血，以及用于宏基因组鸟枪法测序（shotgun metagenomics）的粪便样本。健康对照分别在第0个月和第6个月进行采样。
结果：本研究发现结核病患者与健康对照的肠道菌群组成存在显著差异。尽管在抗结核治疗结束时，患者肠道菌群已趋近于健康对照水平，但多数菌群类群的丰度差异在第15个月时仍持续存在。与此同时，研究观察到血浆代谢物（包括色氨酸、三羧酸循环相关代谢物）与细胞因子水平的紊乱。部分与炎症通路相关的脂肪酸与若干菌群类群的丰度呈负相关。
结论：本研究观察到抗结核治疗期间及治疗后第15个月时，肠道菌群的组成与功能均发生改变。诸多细菌类群丰度变化以及与炎症相关的代谢物紊乱在第15个月时仍未恢复正常。本研究提示，抗结核药物与肠道菌群可能对结核病转归、治疗应答以及未来结核感染易感性产生潜在影响。