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Introduction <p>Tuberculosis remains one of the world’s deadliest infectious diseases. The pathophysiology of the two manifestations of <i>Mycobacterium tuberculosis</i> infection, pulmonary TB (PTB) and extrapulmonary TB (EPTB) is still not fully understood. Understanding the metabolic profile of both disease manifestations in patients is important for developing therapeutic approaches and molecular diagnosis.</p> Objective <p>The current study aimed to elucidate differences in the gut metabolic profile of PTB and EPTB patients compared to healthy controls (HCs).</p> Method <p>We used an untargeted approach through <sup>1</sup>H Nuclear Magnetic Resonance (NMR) spectroscopy to perform metabolomic profiling of stool samples from 77&#xa0;TB patients [pulmonary TB (PTB, <i>n</i> = 33), cervical lymph node TB (CrLNTB, <i>n</i> = 30), abdominal TB (ATB, <i>n</i> = 14)], and 30 HCs. Multivariate and univariate analyses were performed to identify the differential gut metabolites associated with TB patients.</p> Results <p>PTB patients showed greater metabolic perturbation than either EPTB group, with 24 metabolites significantly altered compared to 13 in ATB and 12 in CrLNTB, relative to HCs (adjusted <i>p</i> &lt; 0.05). Each TB subtype displayed distinct metabolic profiles, yet several metabolites were commonly altered across all TB groups, including valine, N-formyl-L-methionine, choline, dimethylsulfone, tryptophan, valerate, N-acetylglutamate, creatine, and malonate. In the combined TB cohort versus controls, the most discriminatory metabolites were valine and N-formyl-L-methionine (AUC ≥ 0.80). Overall, these findings offer insights into the gut metabolome of TB patients in India and characterize for the first time metabolic perturbations in EPTB patients.</p> Conclusion <p>The study highlights the metabolic disruptions associated with PTB and EPTB patients.</p>

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NMR based human gut metabolomic profiling reveals altered metabolites associated with pulmonary and extra-pulmonary tuberculosis

  • 期刊论文

  • 发表日期：

    2025年11月29日

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  • Vishal Sharma,
  • Anoop Singh,
  • Sonam Sharma,
  • Mohita Gaur,
  • Arun Kumar Malaisamy,
  • Deepti Rawat,
  • Anjali Yadav,
  • Bolaji Fatai Oyeyemi,
  • Aarushi Vasudeva,
  • Anil Chaudhry,
  • Ashwani Khanna,
  • Vishal Khanna,
  • Sheelu Lohiya,
  • Reema Arora,
  • Anannya Bandyopadhyay,
  • Neel Sarovar Bhavesh,
  • Yogendra Singh,
  • Richa Misra

摘要

Introduction

Tuberculosis remains one of the world’s deadliest infectious diseases. The pathophysiology of the two manifestations of Mycobacterium tuberculosis infection, pulmonary TB (PTB) and extrapulmonary TB (EPTB) is still not fully understood. Understanding the metabolic profile of both disease manifestations in patients is important for developing therapeutic approaches and molecular diagnosis.

Objective

The current study aimed to elucidate differences in the gut metabolic profile of PTB and EPTB patients compared to healthy controls (HCs).

Method

We used an untargeted approach through 1H Nuclear Magnetic Resonance (NMR) spectroscopy to perform metabolomic profiling of stool samples from 77 TB patients [pulmonary TB (PTB, n = 33), cervical lymph node TB (CrLNTB, n = 30), abdominal TB (ATB, n = 14)], and 30 HCs. Multivariate and univariate analyses were performed to identify the differential gut metabolites associated with TB patients.

Results

PTB patients showed greater metabolic perturbation than either EPTB group, with 24 metabolites significantly altered compared to 13 in ATB and 12 in CrLNTB, relative to HCs (adjusted p < 0.05). Each TB subtype displayed distinct metabolic profiles, yet several metabolites were commonly altered across all TB groups, including valine, N-formyl-L-methionine, choline, dimethylsulfone, tryptophan, valerate, N-acetylglutamate, creatine, and malonate. In the combined TB cohort versus controls, the most discriminatory metabolites were valine and N-formyl-L-methionine (AUC ≥ 0.80). Overall, these findings offer insights into the gut metabolome of TB patients in India and characterize for the first time metabolic perturbations in EPTB patients.

Conclusion

The study highlights the metabolic disruptions associated with PTB and EPTB patients.