The gut-lung axis in tuberculosis: A new frontier in immunomodulation and microbiota-directed therapeutic strategies

Tuberculosis (TB) is a transmissible disease that contributes to the global health burden due to drug resistance. The gut-lung axis is an emerging and promising frontier for understanding Mycobacterium tuberculosis (MTB) pathogenesis and disease progression via gut and lung bidirectional communication. Increasing evidence highlights that regulation in gut and lung microbial communities, termed dysbiosis, influences homeostatic conditions, innate and adaptive responses, and susceptibility to TB. Growing research has witnessed a paradigm shift toward the immunological interplay between gut microbiota and lung microbiota, and modulation in TB. This review deals with the interplay of immune cells and gut microbiota in TB, highlighting the importance of innate and adaptive responses in stabilizing the dysbiosis and inflammation. Host-directed therapies such as probiotics, prebiotics, synbiotics, short-chain fatty acids (SCFAs), and fecal microbiota transplantation support the stabilization of gut microbiota and maintain the disease severity. Moreover, personalized microbiota therapies, such as bacteriophage therapy, diagnostic agents, and biomarkers, are explored for their several roles in maintaining the eubiosis condition. We also highlight the future perspective of addressing the knowledge gap to develop a personalized and combined approach to novel drug delivery systems and host-directed therapies. This review provides an in-depth outline of the gut-lung axis as a potential therapeutic intervention, offering a conceptual framework for developing next-generation, microbiota-directed therapies to suppress and combat MTB infection.