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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.

Sputum microbiota profiles of treatment-naïve TB patients in Uganda before and during first-line therapy