Advances in our understanding of the lung-gut axis in tuberculosis

Abstract Human and animal studies have supported the existence of the gut-lung axis, where gastrointestinal commensals and their products can modulate lung immune function. The role of a balanced, healthy gut microbiota and its restoration may impact the microbiota in the lung. Yet the robustness of this evidence varies considerably, with many studies having considerable limitations. Intestinal microbiota diversity is decreased in pulmonary TB patients, and changes in the intestinal microbiota after Mycobacterium tuberculosis infection have been reported, underscoring the bidirectionality of the lung-gut axis. These changes may be associated with the progression of TB, influencing the microbiota and immunity homeostasis in those receiving anti-TB treatment. The crosstalk between the gut and the lung is increasingly recognized as a key modulator in the development, progression, and treatment outcomes of tuberculosis (TB). A protective role of the intestinal microbiota against lung infections through its role in macrophage activation makes it a promising approach as anti-TB adjunct therapy. This mini review synthesizes current understanding of gut-lung interactions in TB pathogenesis, appraising strengths and limitations of the literature, clarifying areas of consensus versus speculation, highlighting where findings remain preliminary, summarizing the impact of anti-TB treatment on microbial communities, and discussing future directions for microbiota-informed interventions to improve patient outcomes.