Sputum microbiota profiles of patients with rifampicin-resistant tuberculosis during the intensive-phase treatmentOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat Was Studied?
This was a longitudinal observational study examining how the sputum (respiratory) microbiota of patients with rifampicin-resistant tuberculosis (RR-TB) compares to healthy individuals and whether it changes over the course of the six-month intensive phase of second-line anti-TB treatment. Sputum samples were profiled by 16S rRNA gene sequencing targeting the V1–V3 region on the Illumina HiSeq 2500 platform. Investigators compared community composition, alpha and beta diversity, and LEfSe-defined differential taxa across three groups, and used PICRUSt2 to predict shifts in microbial metabolic pathways. A candidate genus-based classifier was also evaluated for diagnostic discrimination.
Who Was Studied?
The cohort comprised 14 RR-TB patients and 14 healthy controls recruited at Guangzhou Chest Hospital, Guangzhou, China, between May 2019 and July 2020. RR-TB patients were sampled at two timepoints, at baseline before treatment (DR0) and again after six months of intensive-phase second-line therapy (DR6), while healthy controls (H) provided a single comparison group. All specimens were sputum, sampling the lower respiratory niche relevant to pulmonary TB.
What Were the Key Findings?
RR-TB patients had significantly lower microbial diversity than healthy controls across Chao1, observed richness, Shannon, Simpson, and Faith's phylogenetic diversity, and beta-diversity analysis (PERMANOVA R² = 0.20, p = 0.001) showed RR-TB communities were compositionally distinct and more dispersed than the tightly clustered healthy group. RR-TB sputum was enriched for pathobionts including Streptococcus, Granulicatella, and Lautropia, whereas healthy controls were enriched for the commensals Fusobacterium and Prevotella; after treatment, Haemophilus and the phylum Bacteroidetes became more prominent. Predicted metabolic capacity was broadly reduced in RR-TB (including UDP-glucose biosynthesis, pyruvate fermentation, and amino acid metabolism), and a five-genus classifier distinguished RR-TB from healthy controls with an AUC of 0.94. Notably, no significant diversity or compositional recovery occurred between baseline and six months (DR0 vs DR6, p_adj = 0.577).
What Are the Implications?
The findings indicate that RR-TB is associated with a depleted, dysbiotic respiratory microbiota that was not reversed by six months of intensive-phase second-line treatment, suggesting that the disease state, rather than the antibiotics alone, primarily shapes the observed community structure. The persistence of dysbiosis through therapy, together with a discriminating genus signature, points to potential roles for respiratory microbiota in RR-TB pathogenesis and as a candidate diagnostic adjunct. These associations are drawn from a small single-center cohort and cannot establish causality, and antibiotic exposure remains a likely confounder of specific taxonomic shifts (such as the post-treatment rise in Haemophilus); larger, controlled studies are needed before clinical application.