Interplay Between Gut Microbiota, Host Immunity, and Lung Pathology in TB Patients

Immunomodulation of the gut microbiota plays a critical role in the host anti-TB response, aiding in the prevention of TB infection, slowing latency progression, reducing disease severity, and lowering the incidence of drug resistance and coinfection. A positive correlation has been found between gut microbiota and peripheral CD4+ T cell count in TB patients. Many anti-TB regimens include broad-spectrum antibiotics like rifampicin and moxifloxacin, which are used at high intensity and for extended periods, potentially exerting selection pressure on gut flora. Anti-TB drugs have been shown to disrupt the gut microbiome and weaken host immunity to MTB. Studies in MDR-TB patients indicate that prolonged use of second-line drugs depletes intestinal flora.

Most TB patients have underlying conditions such as diabetes, chronic kidney disease, or immunosuppression. Notably, T2DM triples the risk of developing TB, and gut microbes may act as key mediators in the link between TB and T2DM. Cytokines such as IL-10, TNF‑α, IFNs I–III, TGF‑β, IL‑35, and regulatory T cells (T‑regs) all significantly influence host immune responses to MTB. Aging TB patients also exhibit reduced respiratory clearance and weakened lung immune defenses, predisposing them to respiratory infections.

Over two-thirds of TB patients experience lasting structural lung changes. Despite treatment, these changes are often irreversible. PTB patients frequently show damage to bronchial mucosa, pulmonary edema, proliferative lesions, and caseous necrosis—conditions conducive to pathogenic colonization. Lung fibrosis and cavitation, in particular, may promote active TB coinfection and further impair lung function. The rise in invasive procedures and structural lung damage has also led to increased fungal and opportunistic infections. Bronchodilation is believed to impair mucociliary clearance, contributing to pathogen retention in the bronchial tree.

Source:

1. Wu, Y., Wang, C. and Li, Y., 2025. Status and outlook of pulmonary tuberculosis coinfection. Journal of Research in Medical Sciences, 30(1), p.34.