There is limited information on microbiota dynamics in tuberculosis (TB) in Africa. Here, we investigated changes in microbiota composition, abundance, co-occurrence and community remodelling relative to clinical parameters, among treatment-naive pulmonary TB patients at Mulago National Referral Hospital in Kampala, Uganda. We sequenced 205 sputum samples from 120 patients before initiating anti-TB therapy (baseline) and during treatment follow-up (at months 2 and 5). A total of 8.6 million high quality sequences were generated, yielding 8,180 operational taxonomic units (OTUs), 18 phyla and 333 genera. A sputum sample on average generated 44,992 sequences, yielding 6,580 OTUs, 4 phyla and 36 genera. The sputum microbiota core comprised of 34 genera and it was remarkably stable during treatment. Month 2 was characterized by a significant mean reduction in core microbiota biomass, limited variance changes and general lack of entropy. However, variance and entropy recovered at month 5. Co-occurrence patterns were predominated by accessory genera at baseline but their abundance significantly reduced during treatment. Our findings reveal discernible sputum microbiota signals associated with first-line anti-TB therapy, with potential to inform treatment response monitoring in developing countries.

No 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.