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Shivakoti R, Newman JW, Hanna LE, et al. Host Lipidome and Tuberculosis Treatment Failure. Eur Respir J. 2021;doi: 10.1183/13993003.04532-2020.
Shivakoti, R., Newman, J. W., Hanna, L. E., Queiroz, A. T. L., Borkowski, K., Gupte, A. N., Paradkar, M., Satyamurthi, P., Kulkarni, V., Selva, M., Pradhan, N., Shivakumar, S. V. B. Y., 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. (2021). Host Lipidome and Tuberculosis Treatment Failure. The European respiratory journal, . https://doi.org/10.1183/13993003.04532-2020
Shivakoti, Rupak, et al. "Host Lipidome and Tuberculosis Treatment Failure." The European respiratory journal vol. (2021). doi: https://doi.org/10.1183/13993003.04532-2020
Shivakoti R, Newman JW, Hanna LE, Queiroz ATL, Borkowski K, Gupte AN, Paradkar M, Satyamurthi P, Kulkarni V, Selva M, Pradhan N, Shivakumar SVBY, Natarajan S, Karunaianantham R, Gupte N, Thiruvengadam K, Fiehn O, Bharadwaj R, Kagal A, Gaikwad S, Sangle S, Golub JE, Andrade BB, Mave V, Gupta A, Padmapriyadarsini C. Host Lipidome and Tuberculosis Treatment Failure. Eur Respir J. 2021 Jun 17; doi: 10.1183/13993003.04532-2020. Epub 2021 Jun 17. PMID: 34375300.
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Eur Respir J. 2021 Jun 17; doi: 10.1183/13993003.04532-2020. Epub 2021 Jun 17.

Host Lipidome and Tuberculosis Treatment Failure.

The European respiratory journal

Rupak Shivakoti, John W Newman, Luke Elizabeth Hanna, Artur T L Queiroz, Kamil Borkowski, Akshay N Gupte, Mandar Paradkar, Pattabiraman Satyamurthi, Vandana Kulkarni, Murugesh Selva, Neeta Pradhan, Shri Vijay Bala Yogendra Shivakumar, Saravanan Natarajan, Ramesh Karunaianantham, Nikhil Gupte, Kannan Thiruvengadam, Oliver Fiehn, Renu Bharadwaj, Anju Kagal, Sanjay Gaikwad, Shashikala Sangle, Jonathan E Golub, Bruno B Andrade, Vidya Mave, Amita Gupta, Chandrasekaran Padmapriyadarsini

Affiliations

  1. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA [email protected].
  2. Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA.
  3. Obesity and Metabolism Research Unit, United States Department of Agriculture, Western Human Nutrition Research Center, Agricultural Research Service, Davis, CA, USA.
  4. Department of Nutrition, University of California, Davis, CA, USA.
  5. West Coast Metabolomics Center, University of California, Davis, CA, USA.
  6. National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India.
  7. Instituto Goncalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.
  8. Multinational Organization Network Sponsoring Translational and Epidemiological Research, Salvador, Brazil.
  9. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  10. Byramjee-Jeejeebhoy Medical College-Johns Hopkins University Clinical Research Site, Pune, India.
  11. Johns Hopkins University - India office (Center for Clinical Global Health Education), Pune, Maharashtra, India.
  12. Byramjee-Jeejeebhoy Government Medical College, Pune, India.
  13. Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil.
  14. Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil.
  15. Curso de Medicina, Universidade Salvador (UNIFACS), Laureate International Universities, Salvador, Brazil.
  16. Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, Brazil.
  17. Equal contribution.

PMID: 34375300 DOI: 10.1183/13993003.04532-2020

Abstract

INTRODUCTION: Host lipids play important roles in Tuberculosis (TB) pathogenesis. Whether host lipids at TB treatment initiation (baseline) affect subsequent treatment outcomes has not been well-characterised. We utilised unbiased lipidomics to study the prospective association of host lipids with TB treatment failure.

METHODS: A case-control study (n=192), nested within a prospective cohort study, was used to investigate the association of baseline plasma lipids with TB treatment failure among adults with pulmonary TB. Cases (n=46) were defined as TB treatment failure, while controls (n=146) were those without failure. Complex lipids and inflammatory lipid mediators were measured using liquid chromatography mass spectrometry techniques. Adjusted least square regression was used to assess differences in groups. In addition, machine learning identified lipids with highest area under the curve (AUC) to classify cases and controls.

RESULTS: Baseline levels of 32 lipids differed between controls and those with treatment failure after false discovery rate adjustment. Treatment failure was associated with lower baseline levels of cholesteryl esters (CE) and oxylipin, and higher baseline levels of ceramides and triglycerides compared to controls. Two CE lipids combined in a unique classifier model provided an AUC of 0.79 (0.65-0.93) in the test dataset for prediction of TB treatment failure.

CONCLUSIONS: We identified lipids, some with known roles in TB pathogenesis, associated with TB treatment failure. A lipid signature with prognostic accuracy for TB treatment failure was also identified. These lipids could be potential targets for risk-stratification, adjunct therapy and treatment monitoring.

Copyright ©The authors 2021. For reproduction rights and permissions contact [email protected].

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