From microbiome to outcome: the cascading effects of combining acid suppressants with anti-tuberculosis therapy.

Gastrointestinal adverse reactions occur in up to 71.8% of patients receiving anti-tuberculosis drugs (ATDs), and acid-suppressing agents are frequently co-prescribed to alleviate these symptoms. Direct evidence from human studies demonstrates that ATDs alone reduce gut microbial diversity, deplete short-chain fatty acid (SCFA)-producing bacteria, and promote opportunistic pathogen overgrowth. Concurrently, acid suppressants, particularly proton pump inhibitors (PPIs), raise intragastric pH and facilitate oral-to-gut translocation of bacteria, independently disrupting microbiota composition and metabolic pathways. In this review, we systematically examine the distinct effects of ATDs and acid suppressants on the gut microbiota, the role of the gut-lung axis in tuberculosis immunity, and, on the basis of mechanistic evidence, propose a theoretical cascade under dual exposure: synergistic microbiota depletion, dual metabolic pathway inhibition, immune homeostasis imbalance, and potentially worsened clinical outcomes. This cascade represents a hypothesis-generating framework derived from preclinical and mechanistic studies, rather than an established clinical pathway, and the critical links from dysbiosis to delayed sputum conversion, poor lesion resolution, or increased drug-induced liver injury currently lack direct human confirmation. On the basis of the available evidence, we recommend that clinicians strictly follow indications for acid suppressants, prefer H₂ receptor antagonists(H