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不同抗结核治疗效果对患者肠道菌群及免疫状态的影响

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目的 研究不同治疗效果的结核患者肠道菌群、免疫功能,进一步探索不同治疗效果的结核患者之间是否存在差异菌群、免疫指标.方法 收集2020年1月-2021年2月长沙中心医院107例初治后的结核患者,通过查阅住院病历记录和采用面对面问卷访谈、登记的结果分为疗效不良组(n=32)和疗效良好组(n=75).采集患者粪便和血液样本,通过高通量测序、生物信息学技术以及流式细胞术、ELISA、结核药敏等相关技术,比较不同疗效组间样本肠道菌群多样性、免疫功能的差异.结果 与疗效不良组比较,疗效良好组γ-干扰素(IFN-γ)、CD4+%水平升高,肿瘤坏死因子(TNF-α)水平降低,差异均有统计学意义(t=2.222、2.377、2.104,P均<0.05),而两组白细胞介素4(1L-4)、IL-10、CD3+%、CD4+/CD8+差异均无统计学意义(P均>0.05).从目、科、属层面分析,未分类的丹毒丝菌在两组间差异均有统计学意义(U=983、983、982,P均<0.05),其余细菌差异均无统计学意义(P均>0.05);从细菌代谢及表型预测结果来看,两组在非同源末端连接、咖啡因代谢、吲哚生物碱合成及类固醇合成等细菌代谢功能方面差异均有统计学意义(Z=0.999、0.999、0.999、0.999,P均<0.05);在需氧菌化能异养、宿主共生、芳香化合物降解、碳氢化合物降解和硝酸盐还原等功能方面差异均有统计学意义(Z=0.179、0.179、0.179、0.179、0.179,P均<0.05);在感染耐药细菌方面,两组在感染耐多药结核分枝杆菌差异有统计学意义(x2=8.698,P<0.05).结论 疗效不良的结核患者免疫功能较疗效良好的患者损伤严重;未分类的丹毒丝菌属可能是影响肺结核患者疗效不良的重要因素之一;肠道菌群的代谢功能低下、肠道菌群紊乱以及感染耐多药结核杆菌均对最终疗效有影响.
The impact of different anti tuberculosis treatment effects on the gut microbiota and immune status of patients
Objective To study the gut microbiota and immune function of tuberculosis patients with different treatment effects,and further explore whether there were differences in microbiota and immune indicators among tuberculosis patients with different treatment effects.Methods A total of 107 patients with tuberculosis after initial treatment in the Changsha Central Hospital from January 2020 to February 2021 were collected and divided into poor efficacy group(n=32)and good efficacy group(n=75)by consulting inpatient medical records and using face-to-face questionnaire interview registration results.Patient and blood samples were collected,and the diversity of intestinal flora and immune function between different groups were compared by high-throughput sequencing,bioinformatics,flow cytometry,ELISA and tuberculosis susceptibility.Results Compared with the poor efficacy group,IFN-γ and CD4+%of the good efficacy group were increased,and TNF-α levels were decreased;the differences were statistically significant(t=2.222,2.377,2.104;all P<0.05),while there was no statistical significance(P>0.05)in IL-4,11-10,CD3+%and CD4+/CD8+.From the perspective of order,family,and genus,the differences were statistically significant(U=983,983,982;all P<0.05)between unclassified erysipelas and other bacteria(P>0.05).From the results of bacterial metabolism and phenotype prediction,there were significant differences(Z=0.999,0.999,0.999,0.999;all P<0.05)between the two groups in bacterial metabolic functions such as non-homologous end connections,caffeine metabolism,indole alkaloid synthesis,and steroid synthesis;there were significant differences(Z=0.179,0.179,0.179,0.179,0.179;all P<0.05)in aerobic bacterial heterotrophic,host symbiosis,aromatic compound degradation,hydrocarbon degradation,and nitrate reduction functions.In terms of drug-resistant bacteria,the difference was statistically significant(x2=8.698,P<0.05)between the two groups in multidrug-resistant Mycobacterium tuberculosis.Conclusions It had been preliminarily confirmed that tuberculosis patients with poor treatment effects had more severe damage to their immune function than those with good treatment effect.It was found that there was a significant difference in the unclassified genus of Erysipella between the two groups,might suggesting that it could be one of the important factors affecting the poor treatment effect of pulmonary tuberculosis patients.The metabolic dysfunction of gut microbiota,disruption of gut microbiota,and infection with multidrug-resistant mycobacterium tuberculosis might have an impact on the final therapeutic effect.

TuberculosisGut microbiota16S rRNA sequencingAnti-tuberculosis treatment

喻容、汤文、易一行、向延根

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湖南中医药大学第二附属医院医学检验中心,湖南长沙 410004

湖南省人民医院检验科,湖南长沙 410005

长沙市中心医院检验科,湖南长沙 410006

结核分枝杆菌 肠道菌群 16S rRNA测序 抗结核治疗

湖南省卫健委科研项目湖南省自然科学基金医卫行业联合基金项目

2021110000972024JJ9454

2024

热带医学杂志
广东省寄生虫学会 中华预防医学会

热带医学杂志

CSTPCD
影响因子:0.643
ISSN:1672-3619
年,卷(期):2024.24(7)
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