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SUMMARY Clinical symptoms of active tuberculosis (TB) can range from a simple cough to more severe reactions, such as irreversible lung damage and, eventually, death, depending on disease progression. In addition to its clinical presentation, TB has been associated with several other disease-induced systemic complications, such as hyponatremia and glucose intolerance. Here, we provide an overview of the known, although ill-described, underlying biochemical mechanisms responsible for the clinical and systemic presentations associated with this disease and discuss novel hypotheses recently generated by various omics technologies. This summative update can assist clinicians to improve the tentative diagnosis of TB based on a patient’s clinical presentation and aid in the development of improved treatment protocols specifically aimed at restoring the disease-induced imbalance for overall homeostasis while simultaneously eradicating the pathogen. Furthermore, future applications of this knowledge could be applied to personalized diagnostic and therapeutic options, bettering the treatment outcome and quality of life of TB patients.

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