摘要目的:分析活动性肺结核患者与健康对照者肠道菌群在物种组成、丰度上的差异，识别并评估特定菌群作为生物标志物区分两组人群的潜能。方法:以2017年9月至2019年9月在四川、江苏、上海3个市区级结核病定点医疗机构收治的活动性肺结核患者88例为病例组，其中男65例，女20例，年龄（44.2±15.7）岁。同期在当地体检人群中招募无结核病史的健康人62名为对照组，其中男33名，女29名，年龄（41.4±11.9）岁。采用16S rRNA基因测序技术检测两组人群的粪便样本，分析两组研究对象肠道菌群的多样性差异，以及门和属水平上的物种组成和丰度差异，采用随机森林方法构建预测模型，探索特定菌群是否可以作为区分结核病患者和健康人群的生物标志物。结果:α多样性分析结果表明，病例组肠道菌群物种丰富度和均匀度低于对照组，差异有统计学意义（ P<0.001），两组人群的肠道菌群整体构成差异有统计学意义（基于Bray-Curtis距离， P<0.001）。与对照组相比，病例组肠道菌群中机会致病菌相对富集，而部分产生短链脂肪酸的有益菌丰度较少，由毛螺菌属（ Lachnospira）、毛螺菌科ND3007组（ Lachnospiraceae ND3007 group）、罗斯拜瑞菌属（ Roseburia）3个菌属训练的随机森林分类器判别两组人群的准确率为76.67%，曲线下面积（AUC）=75.29%（95% CI：0.661~0.845）。 结论:活动性肺结核患者与健康人群的肠道菌群存在差异，特定菌群有作为生物标志物区分两组人群的潜能。

abstractsObjective:To analyze the differences in the composition and abundance of gut microbiota between patients with active pulmonary tuberculosis and healthy controls, and to identify the specific bacteria as biomarkers to distinguish between the two groups.Methods:Patients with active pulmonary tuberculosis treated in three municipal designated tuberculosis medical institutions in Sichuan, Jiangsu and Shanghai from September 2017 to September 2019 were selected as the case group ( n=88), and the healthy people without a history of tuberculosis from the same regions were recruited as the control group ( n=62). The fecal samples of the two groups were detected by 16S rRNA gene sequencing, and the differences of gut microbiota diversity, community composition and relative abundance at phylum and genus level from the two groups were analyzed. The random forest method was used to construct a predictive model to assess whether the specific bacterial flora could be used as biomarkers to distinguish tuberculosis patients from healthy people. Results:The alpha diversity analysis showed that the species richness and evenness of gut microbiota in tuberculosis patients were significantly lower than those in healthy controls ( P<0.001). There was a statistically significant difference in the composition of microbiota between the two groups (Bray-Curtis distance, P<0.001). In the gut microbiota of tuberculosis patients, opportunistic pathogens were relatively enriched, while some of the beneficial bacteria that can produce short-chain fatty acids were less abundant. The discrimination accuracy of the random forest model composed of Lachnospira, Lachnospiraceae ND3007 group and Roseburia was 76.67%, with area under the curve (AUC) being 75.29% (95% CI: 0.661-0.845). Conclusion:There were differences in gut microbiota between patients with active pulmonary tuberculosis and healthy people, and specific bacterial flora showed the potential to be used as biomarkers to distinguish between the two groups.