Metabolomics and Respiratory Diseases

Metabolomics focuses on endogenous small molecules with relative molecular masses below 1000, as substrates and products of various metabolic pathways. Based on nuclear magnetic resonance (NMR), liquid chromatography-mass spectrometer (LC-MS), gas chromatography-mass spectrometer (CC-MS) and other metabolic analysis platforms, qualitative and quantitative analysis of small molecule metabolites to find specific biomarkers and reveal changes in metabolic pathways.

Metabolomics Research Methods

The complete metabolomics research approach focuses on sample pre-treatment, sample analysis data processing and analysis to elucidate the relevant biological significance.

In terms of sample pretreatment, the main sources of biological samples for metabolomics research are biological fluids (urine, blood, saliva, etc.) tissues and cells. Pretreatment of biological fluids can be done by precipitated protein, liquid-liquid extraction, and solid-phase extraction, while tissues and cells can be extracted by ultrasonic fragmentation. Samples are obtained and stored in liquid nitrogen or -80℃ refrigerator.

NMR, LC-MS and GC-MS techniques are currently used as platforms for metabolomics analysis. The data obtained after instrumental analysis are preprocessed by MarkerLynx, MassHunter, XCMS, MATLAB and SIMCA-P software. Pattern recognition methods such as principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DS) are used to build models and screen differential metabolites.

In combination with metabolomics databases such as HMDB (Human Metabolome Database), KEGG (Kyoto Encyclopedia of Genes and Genomes), METLIN and NIST (National Institute of Standards and Technology), we search for the location of differential metabolites in metabolic pathways and analyze the relevant biological mechanisms.

Fig 1. Metabolomics Investigations of Respiratory Diseases (Ho et al., 2018)

Metabolomics in Respiratory Diseases

Bronchial asthma

Bronchial asthma is a complex and heterogeneous disease with a high rate of underdiagnosis and misdiagnosis, and recurrent attacks can lead to complications such as chronic obstructive pulmonary disease, emphysema, and pulmonary heart disease. Mass spectrometry-based metabolomics can sensitively capture metabolic fluctuations and pathological alterations in asthma patients in vivo. It provides a better method for early diagnosis and severity assessment of asthma by analyzing small molecule metabolites of substrates and products of various metabolic pathways in vivo to find biomarkers of the disease.

Fig 2. Figure depicts the main metabolic comorbidities of chronic lung diseases (Papaioannou et al., 2018).

Chronic obstructive pulmonary disease (COPD)

COPD is a common heterogeneous respiratory disease characterized by persistent and incompletely reversible airflow limitation. Potential biomarkers significantly related to lung function parameters can be analyzed by detection with LC-MS technology. Metabolomic studies have shown that imbalances in amino acid metabolism, lipid metabolism, energy production pathways, oxidative and antioxidant may lead to local and systemic inflammation by activating nuclear factor κ light chain enhancers of activated B-cell signaling pathways and releasing inflammatory cytokines. In addition, they may cause protein malnutrition and oxidative stress and contribute to the development and progression of COPD.

Tuberculosis

Multivariate and univariate analysis using liquid chromatography-tandem mass spectrometry (LC-MS / MS) was performed to screen for intergroup differential metabolites and identify potential biomarkers of active tuberculosis.

Lung cancer

Lung cancer is the leading cancer type worldwide and accounts for the highest number of deaths due to poor prognosis and difficulties in early detection. Metabolomics is widely used to assess overall metabolic changes in organisms to study cancer development and provide insight into underlying pathophysiology, identify metabolic markers for early prediction and diagnosis of lung cancer, reveal the pathogenesis of lung cancer as well as differentiate between different types of lung cancer and assess the effectiveness of drug therapy for different patients.

References

1. Papaioannou, O., Karampitsakos, T., et al. (2018). Metabolic disorders in chronic lung diseases. Frontiers in medicine, 4, 246.
2. Ho, W. E., & Wong, W. F. (2018). Understanding and Diagnosing Asthma and COPD by Metabolomics. In Genomic Approach to Asthma (pp. 155-177). Springer, Singapore.

Related Sections

Metabolomics Service

Untargeted Metabolomics Service

Blood & Plasma & Serum Metabolomics

Urine Metabolomics