Harnessing patient autophagy flux to transform tuberculosis treatment

Tuberculosis (TB) remains a major global health burden, prompting heightened efforts towards host-directed therapies (HDT). Autophagy, a key antimicrobial and immunomodulatory process, is a promising candidate for HDT. However, despite encouraging preclinical results, autophagy-targeting strategies have shown limited clinical success, in part due to the lack of accurate profiling of patient-derived autophagy flux across the TB spectrum. This gap limits our understanding of baseline autophagy dynamics and hinders the rational design of HDT. This review highlights patient-derived autophagic flux as a dynamic, quantitative readout of autophagy activity and an underutilized element in TB biomarker and therapeutic research. We examine autophagy flux assessment methodologies and propose its role as a biomarker for TB diagnosis, prognosis, and patient stratification in personalized HDT strategies.