Host lipidome and tuberculosis treatment failure

Authors: SHIVAKOTI, RUPAK - Columbia University; Newman, John; HANNA, LUKE - National Institute For Research In Tuberculosis; QUEIROZ, ARTUR - Oswaldo Cruz Foundation; BORKOWSKI, KAMIL - University Of California, Davis; GUPTE, AKSHAY - Johns Hopkins University School Of Medicine; PARADKAR, MANDAR - Johns Hopkins University; SATYAMURTHI, PATTABIRAMAN - National Institute For Research In Tuberculosis; KULKARNI, VANDANA - Johns Hopkins University; SELVA, MURUGESH - National Institute For Research In Tuberculosis; PRADHAN, NEETA - Johns Hopkins University; SHIVAKUMAR, SHRI - Johns Hopkins University; NATARAJAN, S - National Institute For Research In Tuberculosis; KARUNAIANANTHAM, R - National Institute For Research In Tuberculosis; GUPTE, NIKHIL - Johns Hopkins University School Of Medicine; THIRUVENGADAM, KANNAN - National Institute For Research In Tuberculosis; FIEHN, OLIVER - University Of California, Davis; BHARADWAJ, RENU - Byramjee-Jeejeebhoy Government Medical College; KAGAL, ANJU - Byramjee-Jeejeebhoy Government Medical College; GAIKWAD, SANJAY - Byramjee-Jeejeebhoy Government Medical College; SANGLE, SHASHIKALA - Byramjee-Jeejeebhoy Government Medical College; GOLUB, JONATHAN - Johns Hopkins University School Of Medicine; ANDRADE, BRUNO - Oswaldo Cruz Foundation; MAVE, VIDYA - Johns Hopkins University School Of Medicine; GUPTA, AMITA - Johns Hopkins University School Of Medicine; PADMAPRIYADARSINI, C - National Institute For Research In Tuberculosis

Submitted to: European Respiratory Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/24/2021
Publication Date: 1/6/2022
Citation: Shivakoti, R., Newman, J.W., Hanna, L.E., Queiroz, A.T., Borkowski, K., Gupte, A.N., Paradkar, M., Satyamurthi, P., Kulkarni, V., Selva, M., Pradhan, N., Shivakumar, S.V., Natarajan, S., Karunaianantham, R., Gupte, N., Thiruvengadam, K., Fiehn, O., Bharadwaj, R., Kagal, A., Gaikwad, S., Sangle, S., Golub, J.E., Andrade, B.B., Mave, V., Gupta, A., Padmapriyadarsini, C. 2022. Host lipidome and tuberculosis treatment failure. European Respiratory Journal. 59. Article 2004532. https://doi.org/10.1183/13993003.04532-2020.
DOI: https://doi.org/10.1183/13993003.04532-2020

Interpretive Summary: Host lipids can play an important role in Tuberculosis (TB) pathogenesis by affecting susceptibility or resistance to mycobacteria. Whether and how host lipids present prior to TB treatment initiation can affect treatment outcomes has not been well-characterized. In this study, lipidomic techniques were used to investigate a large number of lipids from multiple lipid classes to study the prospective association of host lipids with TB treatment outcomes. To accomplish this goal, a case-control study (n =257) of TB treatment failure was nested within the CTRIUMPH cohort of individuals with active TB. Cases (n =52) were defined as TB treatment failure while controls (n =205) were cured of TB after treatment. A sub-set analysis was also conducted among adults with culture/gene expression confirmed pulmonary TB (PTB) at baseline and culture-confirmed failure or cure. Secondary outcomes were TB recurrence (n =19) and TB-related mortality (n =22). We investigated the association of pre-treatment plasma lipid profiles with adverse treatment outcomes. Complex lipids and inflammatory lipid mediators were measured using liquid chromatography mass spectrometry techniques. Levels of 52 lipids differed between controls and those with treatment failure after correcting for the large number of statistical comparisons being made. In conclusion, we identified lipids, some with known roles in TB pathogenesis, associated with TB treatment failure. These lipids could be potential targets for adjunct therapy and treatment monitoring and serve as the basis for future research on their function.

Technical Abstract: Host lipids play important roles in Tuberculosis (TB) pathogenesis. Whether and how host lipids at TB treatment initiation (baseline) affect treatment outcomes has not been well-characterized. Here, we utilized lipidomics measured by liquid chromatography mass spectrometry to study the prospective association of host lipids with treatment outcomes. A case-control study (n=257) of TB treatment failure was nested within a prospective cohort study of individuals with TB disease. Cases (n=52) were defined as TB treatment failure while controls (n=205) were those without failure. Using adjusted least square regression, baseline levels of 52 lipids differed between cases and controls, with lower alpha-linolenic acid and one of its oxygenated metabolites, and higher ceramides and triglycerides in those with treatment failure. These lipids, some with known roles in TB pathogenesis, could be potential targets for risk-stratification, adjunct therapy and treatment monitoring while serving as the basis for future research on their function.