Int J Med Sci 2021; 18(9):1935-1945. doi:10.7150/ijms.53492

Research Paper

Sputum microbiota as a potential diagnostic marker for multidrug-resistant tuberculosis

Dongzi Lin1,2#, Xuezhi Wang2#, Yanyun Li1#, Wei Wang2, Yumei Li3, Xiaolin Yu3, Bingyao Lin2, Yinwen Chen3, Chunyan Lei2, Xueying Zhang1, Xilin Zhang2, Juan Huang1, Bihua Lin1, Weiqing Yang1, Jie Zhou2, Jincheng Zeng1✉, Xinguang Liu1✉

1. Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, China
2. Department of Laboratory Medicine, Foshan Fourth People's Hospital, Foshan, Guangdong, 528041, China
3. Department of Laboratory Medicine, Dongguan Sixth People's Hospital, Dongguan, Guangdong, 523008, China
#These authors contributed equally.

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Lin D, Wang X, Li Y, Wang W, Li Y, Yu X, Lin B, Chen Y, Lei C, Zhang X, Zhang X, Huang J, Lin B, Yang W, Zhou J, Zeng J, Liu X. Sputum microbiota as a potential diagnostic marker for multidrug-resistant tuberculosis. Int J Med Sci 2021; 18(9):1935-1945. doi:10.7150/ijms.53492. Available from

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The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains makes disease control more complicated, which is the main cause of death in tuberculosis (TB) patients. Early detection and timely standard treatment are the key to current prevention and control of drug-resistant TB. In recent years, despite the continuous advancement in drug-resistant TB diagnostic technology, the needs for clinical rapid and accurate diagnosis are still not fully met. With the development of sequencing technology, the research of human microecology has been intensified. This study aims to use 16 rRNA sequencing technology to detect and analyze upper respiratory flora of TB patients with anti-TB drug sensitivity (DS, n = 55), monoresistance isoniazide (MR-INH, n = 33), monoresistance rifampin (MR-RFP, n = 12), multidrug resistance (MDR, n = 26) and polyresistance (PR, n = 39) in southern China. Potential microbial diagnostic markers for different types of TB drug resistance are searched by screening differential flora, which provides certain guiding significance for drug resistance diagnosis and clinical drug use of TB. The results showed that the pulmonary microenvironment of TB patients was more susceptible to infection by external pathogens, and the infection of different drug-resistant Mtb leads to changes in different flora. Importantly, seven novel microorganisms (Leptotrichia, Granulicatella, Campylobacter, Delfitia, Kingella, Chlamydophila, Bordetella) were identified by 16S rRNA sequencing as diagnostic markers for different drug resistance types of TB. Leptotrichia, Granulicatella, Campylobacter were potential diagnostic marker for TB patients with INH single-resistance. Delftia was a potential diagnostic marker for TB patients with RFP single drug-resistance. Kingella and Chlamydophila can be used as diagnostic markers for TB patients with PR. Bordetella can be used as a potential diagnostic marker for identification of TB patients with MDR.

Keywords: Tuberculosis, drug resistance, sputum microbiota, 16S rRNA sequencing