Metabolite dynamics over the course of anti-tuberculosis treatment in individuals with mild and severe tuberculosis

Mycobacterium tuberculosis (Mtb) manipulates host metabolism to gain nutrients and increase virulence. Despite known alterations in metabolism in individuals with pulmonary tuberculosis (PTB) during anti-tuberculosis (TB) treatment, the effect of disease severity on metabolite dynamics in individuals with PTB remains understudied. We examined metabolite dynamics over the course of anti-TB treatment in individuals diagnosed with mild (N = 8; smear grade of 1 + /2+ and mild chest x-ray (CXR) abnormality) or severe drug-sensitive PTB (N = 8; 3 + smear grade and moderate/advanced CXR abnormality) in a pilot proof-of-concept study compared to controls without TB (N = 7). Semi-targeted metabolomic analysis of plasma was performed using tandem liquid chromatography-mass spectrometry and electrospray ionization mass spectrometry at baseline, one month, and six months after treatment initiation. Our analysis revealed disease severity-specific metabolic profiles as well as those unique to controls. Many metabolites specific to mild or severe TB were involved in the glycerophospholipid and sphingolipid pathways. A subset of glycerophospholipids were enriched at baseline, month 1, and at the endpoint in individuals with mild and severe TB, despite anti-TB treatment. Our results highlight the importance of glycerophospholipid and sphingolipid pathways during Mtb infection and treatment, regardless of disease severity, and suggest that Mtb could induce chronic effects on host metabolism even after treatment.