Abstract
Information on microbiota dynamics in pulmonary tuberculosis (TB) in Africa is scarce. Here, we sequenced sputa from 120 treatment-naïve TB patients in Uganda, and investigated changes in microbiota of 30 patients with treatment-response follow-up samples. Overall, HIV-status and anti-TB treatment were associated with microbial structural and abundance changes. The predominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria and Actinobacteria, accounting for nearly 95% of the sputum microbiota composition; the predominant genera across time were Prevotella, Streptococcus, Veillonella, Haemophilus, Neisseria, Alloprevotella, Porphyromonas, Fusobacterium, Gemella, and Rothia. Treatment-response follow-up at month 2 was characterized by a reduction in abundance of Mycobacterium and Fretibacterium, and an increase in Ruminococcus and Peptococcus; month 5 was characterized by a reduction in Tannerella and Fusobacterium, and an increase in members of the family Neisseriaceae. The microbiota core comprised of 44 genera that were stable during treatment. Hierarchical clustering of this core’s abundance distinctly separated baseline (month 0) samples from treatment follow-up samples (months 2/5). We also observed a reduction in microbial diversity with 9.1% (CI 6–14%) of the structural variation attributed to HIV-status and anti-TB treatment. Our findings show discernible microbiota signals associated with treatment with potential to inform anti-TB treatment response monitoring.
Highlights
Tuberculosis (TB) is a persistent global public health problem and one of the top 10 causes of death worldwide[1,2]
High-throughput sequencing of the variable region of the 16S rRNA gene generated a total of 9,316,821 sequence reads from the 205 sputum samples i.e., 120, 44, and 41
Dysbiosis has been associated with dysregulation of the immune response, which alters the environment in favour of invading/foreign bacteria[10]; we noted a high biomass of the accessory microbiota, which supports the notion that dysbiosis promotes proliferation of bad/foreign bacteria[10] e.g., Actinobacillus, Bergeyella and Fretibacterium that were components of the accessory microbiota. These findings suggest that the accessory microbiota could be playing a critical role in augmenting sputum microbiota dynamics but the pathobiological implication of this remains unclear
Summary
Tuberculosis (TB) is a persistent global public health problem and one of the top 10 causes of death worldwide[1,2]. Following commencement of treatment with anti-TB drugs, sputum microscopy for identification of mycobacteria (in form of acid-fast bacilli, AFB) or where affordable, sputum culturing for Mycobacterium tuberculosis growth is done during the treatment period, usually at months 2 and 5 to monitor treatment response. A sound understanding of the microbiota dynamics in TB is necessary given their emerging importance in human and animal h ealth[11,15] In this context, microbial profiling in TB could advance our knowledge of TB pathogenesis (infection vs active disease) or unravel new ways in which TB diagnostics and management can be improved[7,11,12,13]. We describe the microbial changes associated with critical transitions of anti-TB treatment: pre-treatment (baseline) and treatment response follow-up at months 2 and 5
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