Sputum Microbiota Profiles of Treatment-Naïve TB Patients in Uganda Before and During First-Line Therapy

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-naïve 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.