ORIGINAL ARTICLE Identification of serum metabolic markers for diagnosis of women with dormant genital tuberculosis Elavarasan Subramani 1 • Mainak Dutta 1 • Manivannan Jothiramajayam 2 • Mamata Joshi 3 • Sudha Srivastava 3 • Anita Mukherjee 2 • Baidyanath Chakravarty 4 • Koel Chaudhury 1 Received: 27 February 2016 / Accepted: 22 April 2016 / Published online: 30 April 2016 Ó Springer Science+Business Media New York 2016 Abstract Introduction Genital tuberculosis (GTB) in women is one of the common causes of infertility in emerging countries. As an intracellular pathogen, Mycobacterium tuberculosis in the endometrium significantly alters the host metabolism in dormant GTB cases. Nuclear magnetic resonance (NMR) based metabolic profiling has emerged as a useful tool for identification of biomarkers in biological fluids. Objective To investigate NMR based serum metabolic profile of dormant GTB women as compared to controls. Methods Dormant GTB women (n = 26) and unexplained infertile women (controls; n = 26), healthy proven fertile women undergoing voluntary sterilization (n = 25) and women undergoing recurrent spontaneous miscarriage (RSM) (n = 27) were included in the study. 700 MHz proton NMR spectra of serum collected from these patients were recorded. Multivariate analysis including principal component analysis, partial least squares discriminant analysis and orthogonal projection to latent structure- discriminant analysis was applied to all the spectra. Association of dysregulated serum metabolites with our earlier findings related to altered endometrial tissue metabolites in dormant GTB women was studied using multiple correlation analysis. Results This study indicates a clear metabolic differentia- tion between women with dormant GTB and controls. Metabolites including 3-hydroxybutyrate, succinate, citrate, acetate, L-glutamine, L-lysine, glutamate, L-thre- onine and 1-methyl histidine were found to be significantly upregulated in serum of women with dormant GTB com- pared with controls. Pearson’s correlation analysis showed a significant correlation between the expression of endometrial tissue and serum metabolites. Conclusions The set of identified metabolites may be considered as candidate markers for the diagnosis of dor- mant GTB and help clinicians in early therapeutic management. Keywords Proton nuclear magnetic resonance Á Metabonomics Á Multivariate analysis Á Dormant genital tuberculosis Á Biomarkers 1 Introduction Genital tuberculosis (GTB) in women is an important clinical problem often associated with infertility (Bose 2011; Dam et al. 2006). According to an estimate, 5 % of women seeking infertility treatment have GTB worldwide (Malik 2003). The incidence of GTB in developing soci- eties such as India is reported to be as alarming as 18–19 % (Malik 2003; Das et al. 2008). It is well recognized that the active form of GTB causes irreversible tubal and endometrial damage (Jindal et al. 2010) and even the Electronic supplementary material The online version of this article (doi:10.1007/s11306-016-1042-5) contains supplementary material, which is available to authorized users. & Koel Chaudhury koeliitkgp@gmail.com; koel@smst.iitkgp.ernet.in 1 School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, West Bengal, India 2 Cell Biology and Genetic Toxicology Laboratory, Centre of Advanced Study, Department of Botany, University of Calcutta, Kolkata 700019, West Bengal, India 3 National Facility for High-field NMR, Tata Institute of Fundamental Research, Mumbai 400005, Maharashtra, India 4 Institute of Reproductive Medicine, Salt Lake, Kolkata 700020, West Bengal, India 123 Metabolomics (2016) 12:99 DOI 10.1007/s11306-016-1042-5