Biomarker discovery for tuberculosis using metabolomics

Abstract

Tuberculosis (TB) is the leading cause of death among infectious diseases, and the ratio of cases in which its pathogen Mycobacterium tuberculosis (Mtb) is drug resistant has been increasing worldwide, whereas latent tuberculosis infection (LTBI) may develop into active TB. Thus it is important to understand the mechanism of drug resistance, find new drugs, and find biomarkers for TB diagnosis. The rapid progress of metabolomics has enabled quantitative metabolite profiling of both the host and the pathogen. In this context, we provide recent progress in the application of metabolomics toward biomarker discovery for tuberculosis. In particular, we first focus on biomarkers based on blood or other body fluids for diagnosing active TB, identifying LTBI and predicting the risk of developing active TB, as well as monitoring the effectiveness of anti-TB drugs. Then we discuss the pathogen-based biomarker research for identifying drug resistant TB. While there have been many reports of potential candidate biomarkers, validations and clinical testing as well as improved bioinformatics analysis are needed to further substantiate and select key biomarkers before they can be made clinically applicable.

Exploring the Potential of Exosomes as Biomarkers in Tuberculosis and Other Diseases

“…Metabolites can serve as valuable indicators of a person’s overall health and can be used to diagnose a disease, assess the response to treatment, and monitor disease progression for a wide range of diseases, including tuberculosis, cancer, diabetes, and Alzheimer’s disease. Various metabolites that have been identified in different studies have shown deregulation during tuberculosis infection [ 84 ]. One such category includes amino acids, which play an important role in tuberculosis biology, as they stimulate the host immune response (methionine, glutamine, arginine, and citrulline) and help Mtb to survive cellular stress (tryptophan and asparagine) [ 85 ] ( Figure 2 ).…”

Plasma metabolomic analysis reveals the metabolic characteristics and potential diagnostic biomarkers of spinal tuberculosis

“…This method has been widely used to elucidate pathogenesis, diagnose diseases, and predict prognosis [ 16 ]. However, few metabolomic studies have been conducted on STB [ 17 ].…”

Urinary markers of Mycobacterium tuberculosis and dysbiosis in paediatric tuberculous meningitis cases undergoing treatment

“…Before the coronavirus (COVID-19) pandemic, tuberculosis (TB) was ranked as the leading cause of infectious disease mortalities worldwide [ 1 , 2 ]. Tuberculous meningitis (TBM) is a severe form of extrapulmonary TB, resulting in high morbidity and mortality, especially in children under the age of 12 years [ 3 ].…”

“…Compared to that of pulmonary TB, less research has been conducted on TBM, mainly due to difficulty in attaining research sample material, particularlycerebrospinal fluid, comparatively lower prevalence of TBM and difficulty in diagnosis. Hence, much still needs to be done to better understand Mycobacterium tuberculosis ( M. tb ), the causative agent, in the context of TBM, the subsequent immunopathological interactions and the resulting systemic metabolic adaptations/response of the host, which in turn typically leads to new therapeutic approaches [ 2 – 7 ]. There is also an urgent need for more effective and earlier diagnostic tools to detect TBM, especially in children, at an early stage of the disease.…”