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并且在使用异烟肼-利福平-吡嗪酰胺-乙胺丁醇(HRZE)进行抗结核化疗期间,活动性肺结核患者体内它与粪便代谢物4-羟基-L-脯氨酸和染料木黄酮水平升高有关。

, and associates with increased fecal metabolites -4-Hydroxy-L-proline and Genistein in active pulmonary tuberculosis patients during anti-tuberculosis chemotherapy with isoniazid-rifampin-pyrazinamide-ethambutol (HRZE).

作者信息

Meng Ruijie, Dong Wenya, Gao Jie, Lu Chunrong, Zhang Chenchen, Liao Qinghua, Chen Liang, Wu Huizhong, Hu Jiwen, Wei Wenjing, Jiang Zhenyou

机构信息

Department of Microbiology and Immunology, College of Basic Medicine and Public Hygiene, Jinan University, GuangZhou, 510632 China.

Department of Clinical Laboratory, Guangdong Women and Children Hospital, Guangzhou, 511443 China.

出版信息

Indian J Microbiol. 2022 Sep;62(3):374-383. doi: 10.1007/s12088-022-01003-2. Epub 2022 Mar 24.

Abstract

PURPOSE

To investigated the changes of gut microbiome and fecal metabolome during anti-tuberculosis chemotherapy with isoniazid (H)-rifampin (R)-pyrazinamide (Z)-ethambutol (E).

PATIENTS AND METHODS

(1) In this study, we recruited 168 stool specimens from 49 healthy volunteers without (Mtb), 30 healthy volunteers with latently infected by Mtb, 41 patients with active tuberculosis (ATB), 28 patients with 2-month HRZE treatment and 20 patients with 2-month HRZE followed by 4-month HR treatment. (2) We used 16S rRNA sequencing and an untargeted Liquid Chromatograph Mass Spectrometer-based metabolomics to investigate the changes of gut microbiome and the alteration of fecal metabolome, respectively, during anti-TB chemotherapy.

RESULTS

Mtb infection can reduce the diversity of intestinal flora of ATB patients and change their taxonomic composition, while the diversity of intestinal flora of ATB patients were restored during anti-TB chemotherapy. Especially, family and and their genera and significantly increased in the gut microbiota during anti-TB chemotherapy. Additionally, Mtb infection dynamically regulates fecal metabolism in ATB patients during anti-TB chemotherapy. Interestingly, the altered abundance of fecal metabolites correlated with the altered gut microbiota, especially the change of gut , and was closely related to the change of fecal metabolites such as -4-Hydroxy-L-proline and Genistein caused by Mtb infection or anti-TB chemotherapy.

CONCLUSION

Anti-TB chemotherapy with HRZE can disrupt both gut microbiotas and metabolome in ATB patients. Some specific genera and metabolites are depleted or enriched during anti-TB chemotherapy. Therefore, revealing potential relevance between gut microbiota and anti-TB chemotherapy will provide potential biomarkers for evaluating the therapeutic efficacy in ATB patients.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s12088-022-01003-2.

摘要

目的

研究异烟肼(H)-利福平(R)-吡嗪酰胺(Z)-乙胺丁醇(E)抗结核化疗期间肠道微生物群和粪便代谢组的变化。

患者与方法

(1)本研究收集了49名未感染结核分枝杆菌(Mtb)的健康志愿者、30名潜伏感染Mtb的健康志愿者、41名活动性肺结核(ATB)患者、28名接受2个月HRZE治疗的患者以及20名接受2个月HRZE治疗后再接受4个月HR治疗的患者的168份粪便样本。(2)我们分别使用16S rRNA测序和基于非靶向液相色谱-质谱联用的代谢组学方法,研究抗结核化疗期间肠道微生物群的变化和粪便代谢组的改变。

结果

Mtb感染可降低ATB患者肠道菌群的多样性并改变其分类组成,而ATB患者的肠道菌群多样性在抗结核化疗期间得以恢复。特别是,抗结核化疗期间肠道微生物群中的[具体菌群名称1]科及其[具体属名1]属和[具体菌群名称2]科及其[具体属名2]属显著增加。此外,Mtb感染在抗结核化疗期间动态调节ATB患者的粪便代谢。有趣的是,粪便代谢物丰度的改变与肠道微生物群的改变相关,尤其是肠道[具体菌群名称3]、[具体菌群名称4]和[具体菌群名称5]的变化与Mtb感染或抗结核化疗引起的粪便代谢物如-4-羟基-L-脯氨酸和染料木黄酮的变化密切相关。

结论

HRZE抗结核化疗可破坏ATB患者的肠道微生物群和代谢组。抗结核化疗期间一些特定的属和代谢物会减少或富集。因此,揭示肠道微生物群与抗结核化疗之间的潜在相关性将为评估ATB患者的治疗效果提供潜在的生物标志物。

补充信息

在线版本包含可在10.1007/s12088-022-01003-2获取的补充材料。

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