A novel enterotype enriched with respiratory super-dominant pathobionts is associated with immunosuppression in pulmonary tuberculosis patients

BACKGROUND: Perturbations of the gut microbiota in pulmonary tuberculosis (PTB) patients, often antibiotic-induced, are frequently observed; however, the defining features of this dysbiosis and its relationship with clinical phenotypes remain insufficiently characterized. METHODS: In this cross-sectional study, we collected fecal samples from 66 PTB patients and performed 16S rRNA gene (V3-V4) sequencing. Species-level taxonomic profiling was conducted using the Human Gut Microbiome Analysis Database (HGMAD). Enterotypes were constructed, and their associations with PTB were investigated. The predictive capacity of enterotype-specific microbial signatures (enterosignatures) for clinical phenotypes was assessed. RESULTS: ratio, 0.93 for CRP, 0.78 for CA125, and 0.70 for Mtb positivity. SHapley Additive exPlanation (SHAP) analysis identified Enterobacterales and Veillonella as key negative predictors for T-cell counts, while Streptococcus and Enterobacteriaceae were positive predictors for CRP. In the CA125 model, Veillonella acted as a positive predictor and Enterobacterales as a negative predictor. CONCLUSION: This cross-sectional study identifies a distinct, PTB-associated enterotype (ETE) characterized by enrichment of respiratory pathobionts and associated with altered immune parameters in PTB patients. Enterosignatures derive from ETE represent exploratory biomarkers with promising predictive capacity for clinical outcomes, though their generalizability warrants validation in independent, prospective cohorts.