Gut microbiota composition and diversity before, during, and two months after rifamycin-based tuberculosis preventive therapy.

Tuberculosis (TB) preventive therapy (TPT) is an effective strategy to eliminate TB in low-incidence settings. Shorter TPT regimens incorporating the antimicrobial class of rifamycins are designed to improve adherence and completion rates but carry the risk of modifications to the gut microbiota. We enrolled six subjects diagnosed with latent TB infection (LTBI) who accepted to initiate TPT. We also enrolled six healthy volunteers unexposed to the rifamycins. We profiled the gut microbiota using 16S rRNA amplicon sequencing (V1-V2 region) to document the immediate effect of rifamycin-based TPT on the gut microbiota composition and tracked recovery to baseline two months after TPT. Overall, TPT accounted for 17% of the variance in gut microbial community dissimilarity. This rifamycin-based TPT induced dysbiosis was characterized by a depletion of butyrate-producing taxa (Clostridium-XIVa and Roseburia) and expansion of potentially pathogenic taxa within the Firmicutes and Proteobacteria phyla. Recovery of the gut microbial composition was incomplete two months after TPT. Robust clinical studies are necessary to comprehensively catalogue TPT-induced gut microbiota dysbiosis to inform strategies to mitigate potential long-term sequelae of this important TB control intervention.

16S rRNA gene sequencing of stool samples collected from patients with latent tuberculosis infection before, during, and two months after treatment with 3HP or 4R.

OBJECTIVE: We present 16s rRNA gene sequencing (V1-V2 region) and sample data from a pilot observational cohort study to describe the gut microbiota dynamics of subjects with latent tuberculosis infection (LTBI) treated with daily 600 mg rifampicin for four months (4R) or a weekly dose of 900 mg combination of rifapentine and isoniazid for three months (3HP). Our objectives were to (1) document changes to the gut microbiota immediately following exposure to the rifamycins and (2) document recovery to baseline two months after treatment completion. DATA DESCRIPTION: We enrolled six subjects with subjects with LTBI and prospectively followed them for 5-6 months. Each subject provided stool samples before, during, and two months after treatment. Six healthy controls were sampled in parallel with the patients with LTBIs. We report amplicon sequence variants (ASVs) and taxonomic assignments for 60 stool samples. Additionally, we provide access to the raw amplicon sequences, and subject responses to questionnaires about their diet, medication, and lifestyle changes over the study follow-up period. Furthermore, we provide the concentration of the parent and partially active rifamycin metabolite concentrations measured validated LC-MS-MS assays of phosphate buffer washes of the stool samples collected from the LTBI participants. This comprehensive dataset is a valuable resource for future systematic reviews and meta-analyses of the impact of LTBI therapy on the gut microbiota.