代谢组学在儿童囊性纤维化中的应用进展
Progress in Application of Metabolomics in Childhood Cystic Fibrosis
DOI: 10.12677/ACM.2024.142591, PDF,   
作者: 向仕华, 彭东红*：重庆医科大学附属儿童医院呼吸科，重庆；国家儿童健康与疾病临床医学研究中心，重庆；儿童发育疾病研究教育部重点实验室，重庆；儿科学重庆市重点实验室，重庆
关键词: 代谢组学；囊性纤维化；儿童；应用进展；Metabolism； Cystic Fibrosis； Child； Application Progress
摘要: 囊性纤维化(cystic fibrosis, CF)是一种以肺部疾病伴随多系统受累的遗传性疾病，随着近年来对该病认识的提高及基因检测技术的发展，更多的患儿被诊断出来，但目前对该病的致病机制、诊断、治疗及预后仍处于研究中。代谢组学可以全面系统或有针对性地识别和量化生物样本中的代谢物，对代谢物进行综合评估，使之成为CF研究中的有利工具。本文就代谢组学在儿童CF中的应用进展进行综述，重点概述代谢组学在CF患儿代谢产物特点、慢性炎症、病原学及急性加重期等方面的应用进展。
Abstract: Cystic fibrosis (CF) is a hereditary disease characterized by pulmonary complications and systemic involvement. In recent years, advancements in the comprehension of CF, along with the evolution of genetic testing methodologies, have facilitated increased diagnoses in pediatric populations. However, various aspects including the disease’s etiology, diagnostic approaches, therapeutic interventions, and prognostic factors remain subjects of ongoing research. The field of metab-olomics presents a robust and systematic approach to comprehensively identify and quantify metabolites within biological samples. This capability allows for a comprehensive assessment of metabolite abundance, rendering it an invaluable tool in conducting research pertaining to cystic fibrosis. The present article provides a comprehensive overview of the advancements in metabo-lomics application for pediatric CF patients, with a specific focus on the characterization of metab-olites, chronic inflammation, etiology, and acute exacerbation in children with CF.
文章引用：向仕华, 彭东红. 代谢组学在儿童囊性纤维化中的应用进展[J]. 临床医学进展, 2024, 14(2): 4267-4274. https://doi.org/10.12677/ACM.2024.142591

参考文献

[1] Dickinson, K.M. and Collaco, J.M. (2021) Cystic Fibrosis. Pediatrics in Review, 42, 55-67. [Google Scholar] [CrossRef] [PubMed]
[2] Graeber, S.Y. and Mall, M.A. (2023) The Future of Cystic Fibrosis Treatment: From Disease Mechanisms to Novel Therapeutic Approaches. The Lancet (London, England), 402, 1185-1198. [Google Scholar] [CrossRef] 
[3] Guo, X., Liu, K., Liu, Y., et al. (2018) Clinical and Genetic Characteristics of Cystic Fibrosis in CHINESE Patients: A Systemic Review of Reported Cases. Orphanet Journal of Rare Diseases, 13, Article No. 224. [Google Scholar] [CrossRef] [PubMed]
[4] Guo, J., Garratt, A. and Hill, A. (2022) Worldwide Rates of Di-agnosis and Effective Treatment for Cystic Fibrosis. Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society, 21, 456-462. [Google Scholar] [CrossRef] [PubMed]
[5] O’Sullivan, B.P. and Freedman, S.D. (2009) Cystic Fibrosis. The Lancet (London, England), 373, 1891-1904. [Google Scholar] [CrossRef] 
[6] Sanders, D.B. and Fink A.K. (2016) Background and Epi-demiology. Pediatric Clinics of North America, 63, 567-584. [Google Scholar] [CrossRef] [PubMed]
[7] Ni, Q., Chen, X., Zhang, P., et al. (2022) Systematic Estimation of Cystic Fibrosis Prevalence in Chinese and Genetic Spectrum Comparison to Caucasians. Orphanet Journal of Rare Diseases, 17, Article No. 129. [Google Scholar] [CrossRef] [PubMed]
[8] Clayton, T.A., Lindon, J.C., Cloarec, O., et al. (2006) Pharmaco-Metabonomic Phenotyping and Personalized Drug Treatment. Nature, 440, 1073-1077. [Google Scholar] [CrossRef] [PubMed]
[9] Nicholson, J.K. and Lindon, J.C. (2008) Systems Biology: Metabonomics. Nature, 455, 1054-1056. [Google Scholar] [CrossRef] [PubMed]
[10] Arakaki, A.K., Skolnick, J. and McDonald, J.F. (2008) Marker Metabolites Can Be Therapeutic Targets as Well. Nature, 456, 443. [Google Scholar] [CrossRef] [PubMed]
[11] Stringer, K.A., McKay, R.T., Karnovsky, A., et al. (2016) Metabolomics and Its Application to Acute Lung Diseases. Frontiers in Immunology, 7, Article 44. [Google Scholar] [CrossRef] [PubMed]
[12] Wishart, D.S. (2005) Metabolomics: The Principles and Potential Applications to Transplantation. American Journal of Transplantation, 5, 2814-2820. [Google Scholar] [CrossRef] [PubMed]
[13] Wishart, D.S. (2010) Computational Approaches to Metabolomics. Methods in Molecular Biology (Clifton, NJ), 593, 283-313. [Google Scholar] [CrossRef] [PubMed]
[14] Pinu, F.R., Beale, D.J., Paten, A.M., et al. (2019) Systems Biology and Multi-Omics Integration: Viewpoints from the Metabolomics Research Community. Metabolites, 9, Article 76. [Google Scholar] [CrossRef] [PubMed]
[15] Heckendorf, C., Blum, B.C., Lin, W., et al. (2023) Integration of Metabolomic and Proteomic Data to Uncover Actionable Metabolic Pathways. Methods in Molecular Biology (Clifton, NJ), 2660, 137-148. [Google Scholar] [CrossRef] [PubMed]
[16] Chetty, A. and Blekhman, R. (2024) Multi-Omic Approaches for Host-Microbiome Data Integration. Gut Microbes, 16, Article 2297860. [Google Scholar] [CrossRef] [PubMed]
[17] Joseloff, E., Sha, W., Bell, S.C., et al. (2014) Serum Metabolomics Indicate Altered Cellular Energy Metabolism in Children with Cystic Fibrosis. Pediatric Pulmonology, 49, 463-472. [Google Scholar] [CrossRef] [PubMed]
[18] Esther Jr., C.R., Coakley, R.D., Henderson, A.G., et al. (2015) Metabolomic Evaluation of Neutrophilic Airway Inflammation in Cystic Fibrosis. Chest, 148, 507-515. [Google Scholar] [CrossRef] [PubMed]
[19] O’Connor, J.B., Mottlowitz, M., Kruk, M.E., et al. (2022) Network Analysis to Identify Multi-Omic Correlations in the Lower Airways of Children with Cystic Fibrosis. Frontiers in Cel-lular and Infection Microbiology, 12, Article 805170. [Google Scholar] [CrossRef] [PubMed]
[20] Beckonert, O., Keun, H.C., Ebbels, T.M., et al. (2007) Metabolic Profiling, Metabolomic and Metabonomic Procedures for NMR Spectroscopy of Urine, Plasma, Serum and Tissue Ex-tracts. Nature Protocols, 2, 2692-2703. [Google Scholar] [CrossRef] [PubMed]
[21] Griffin, J.L. and Kauppinen, R.A. (2007) Tumour Metabolomics in Animal Models of Human Cancer. Journal of Proteome Research, 6, 498-505. [Google Scholar] [CrossRef] [PubMed]
[22] Mena-Bravo, A. and Luque de Castro, M.D. (2014) Sweat: A Sample with Limited Present Applications and Promising Future in Metabolomics. Journal of Pharmaceutical and Biomedical Analysis, 90, 139-147. [Google Scholar] [CrossRef] [PubMed]
[23] Serkova, N.J., Standiford, T.J. and Stringer, K.A. (2011) The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses. American Journal of Respiratory and Critical Care Medicine, 184, 647-655. [Google Scholar] [CrossRef] 
[24] Alonso, A., Marsal, S. and Julià A. (2015) Analytical Methods in Untargeted Metabolomics: State of the Art in 2015. Frontiers in Bioengineering and Biotechnology, 3, Article 23. [Google Scholar] [CrossRef] [PubMed]
[25] Sas, K.M., Karnovsky, A., Michailidis, G., et al. (2015) Metabo-lomics and Diabetes: Analytical and Computational Approaches. Diabetes, 64, 718-732. [Google Scholar] [CrossRef] [PubMed]
[26] More, T., RoyChoudhury, S., Gollapalli, K., et al. (2015) Metabolomics and Its Integration with Systems Biology: PSI 2014 Conference Panel Discussion Report. Journal of Proteomics, 127, 73-79. [Google Scholar] [CrossRef] [PubMed]
[27] Markley, J.L., Brüschweiler, R., Edison, A.S., et al. (2017) The Future of NMR-Based Metabolomics. Current Opinion in Biotechnology, 43, 34-40. [Google Scholar] [CrossRef] [PubMed]
[28] Basov, N.V., Rogachev, A.D., Aleshkova, M.A., et al. (2024) Global LC-MS/MS Targeted Metabolomics Using a Combination of HILIC and RP LC Separation Modes on an Organic Monolithic Column Based on 1-Vinyl-1,2,4-Triazole. Talanta, 267, Article 125168. [Google Scholar] [CrossRef] [PubMed]
[29] Bansal, N., Kumar, M. and Gupta, A. (2024) Richer than Pre-viously Probed: An Application of 1H NMR Reveals One Hundred Metabolites Using Only Fifty Microliter Serum. Biophysical Chemistry, 305, Article 107153. [Google Scholar] [CrossRef] [PubMed]
[30] Bjerrum, J.T. (2015) Metabonomics: Analytical Techniques and Associated Chemometrics at a Glance. In: Bjerrum, J., Ed., Methods in Molecular Biology (Clifton, NJ), Vol. 1277, Humana Press, New York, 1-14. [Google Scholar] [CrossRef] [PubMed]
[31] Zamboni, N., Saghatelian, A. and Patti, G.J. (2015) Defining the Metabolome: Size, Flux, and Regulation. Molecular Cell, 58, 699-706. [Google Scholar] [CrossRef] [PubMed]
[32] Yurekten, O., Payne, T., Tejera, N., et al. (2024) MetaboLights: Open Data Repository for Metabolomics. Nucleic Acids Research, 52, D640-D646. [Google Scholar] [CrossRef] [PubMed]
[33] Wishart, D.S., Kruger, R., Sivakumaran, A., et al. (2024) PathBank 2.0—The Pathway Database for Model Organism Metabolomics. Nucleic Acids Research, 52, D654-D662. [Google Scholar] [CrossRef] [PubMed]
[34] 中华医学会儿科学分会呼吸学组, 中华医学会儿科学分会呼吸学组疑难少见病协作组, 国家呼吸系统疾病临床医学研究中心等. 中国儿童囊性纤维化诊断与治疗专家共识[J]. 中华实用儿科临床杂志, 2022, 37(22): 1681-1687.
[35] 田欣伦. 中国人囊性纤维化[J]. 中国实用儿科杂志, 2023, 38(3): 204-209.
[36] Wisniewski, B.L., Shrestha, C.L., Zhang, S., et al. (2020) Metabolomics Profiling of Tobacco Exposure in Children with Cystic Fibrosis. Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society, 19, 791-800. [Google Scholar] [CrossRef] [PubMed]
[37] Esther Jr., C.R., Muhlebach, M.S., Ehre, C., et al. (2019) Mucus Ac-cumulation in the Lungs Precedes Structural Changes and Infection in Children with Cystic Fibrosis. Science Transla-tional Medicine, 11. [Google Scholar] [CrossRef] [PubMed]
[38] Scholte, B.J., Horati, H., Veltman, M., et al. (2019) Oxidative Stress and Abnormal Bioactive Lipids in Early Cystic Fibrosis Lung Disease. Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society, 18, 781-789. [Google Scholar] [CrossRef] [PubMed]
[39] Zemanick, E.T., Sagel, S.D. and Harris, J.K. (2011) The Airway Microbiome in Cystic Fibrosis and Implications for Treatment. Current Opinion in Pediatrics, 23, 319-324. [Google Scholar] [CrossRef] 
[40] Elizur, A., Cannon, C.L. and Ferkol, T.W. (2008) Airway Inflammation in Cystic Fibrosis. Chest, 133, 489-495. [Google Scholar] [CrossRef] [PubMed]
[41] Lepissier, A., Addy, C., Hayes, K., et al. (2022) Inflammation Bi-omarkers in Sputum for Clinical Trials in Cystic Fibrosis: Current Understanding and Gaps in Knowledge. Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society, 21, 691-706. [Google Scholar] [CrossRef] [PubMed]
[42] Wolak, J.E., Esther Jr., C.R., and O’Connell, T.M. (2009) Metabolomic Analysis of Bronchoalveolar Lavage Fluid from Cystic Fibrosis Patients. Biomarkers: Biochemical Indi-cators of Exposure, Response, and Susceptibility to Chemicals, 14, 55-60. [Google Scholar] [CrossRef] [PubMed]
[43] Nichols, D., Chmiel, J. and Berger, M. (2008) Chronic In-flammation in the Cystic Fibrosis Lung: Alterations in Inter- and Intracellular Signaling. Clinical Reviews in Allergy & Immunology, 34, 146-162. [Google Scholar] [CrossRef] [PubMed]
[44] Twomey, K.B., Alston, M., An, S.Q., et al. (2013) Microbiota and Metabolite Profiling Reveal Specific Alterations in Bacterial Community Structure and Environment in the Cystic Fibrosis Airway During Exacerbation. PLOS ONE, 8, e82432. [Google Scholar] [CrossRef] [PubMed]
[45] Hu, Y. and Coates, A. (2012) Nonmultiplying Bacteria Are Profoundly Tolerant to Antibiotics. In: Coates, A., Ed., Antibiotic Resistance. Handbook of Experimental Pharmacology, Vol. 211, Springer, Berlin, Heidelberg, 99-119. [Google Scholar] [CrossRef] [PubMed]
[46] Quinn, R.A., Phelan, V.V., Whiteson, K.L., et al. (2016) Mi-crobial, Host and Xenobiotic Diversity in the Cystic Fibrosis Sputum Metabolome. The ISME Journal, 10, 1483-1498. [Google Scholar] [CrossRef] [PubMed]
[47] Robroeks, C.M., Van Berkel, J.J., Dallinga, J.W., et al. (2010) Metabolomics of Volatile Organic Compounds in Cystic Fibrosis Patients and Controls. Pediatric Research, 68, 75-80. [Google Scholar] [CrossRef] 
[48] Hahn, A., Whiteson, K., Davis, T.J., et al. (2020) Longitu-dinal Associations of the Cystic Fibrosis Airway Microbiome and Volatile Metabolites: A Case Study. Frontiers in Cellular and Infection Microbiology, 10, Article 174. [Google Scholar] [CrossRef] [PubMed]
[49] Bhatt, J.M. (2013) Treatment of Pulmonary Exacerbations in Cystic Fibrosis. European Respiratory Review: An Official Journal of the European Respiratory Society, 22, 205-216. [Google Scholar] [CrossRef] [PubMed]
[50] Laguna, T.A., Reilly, C.S., Williams, C.B., et al. (2015) Metabolomics Analysis Identifies Novel Plasma Biomarkers of Cystic Fibrosis Pulmonary Exacerbation. Pediatric Pulmonology, 50, 869-877. [Google Scholar] [CrossRef] [PubMed]
[51] Montuschi, P., Paris, D., Melck, D., et al. (2012) NMR Spectroscopy Metabolomic Profiling of Exhaled Breath Condensate in Patients with Stable and Unstable Cystic Fibrosis. Thorax, 67, 222-228. [Google Scholar] [CrossRef] [PubMed]
[52] Montuschi, P., Paris, D., Montella, S., et al. (2014) Nuclear Magnetic Resonance-Based Metabolomics Discriminates Primary Ciliary Dyskinesia from Cystic Fibrosis. American Journal of Respiratory and Critical Care Medicine, 190, 229-233. [Google Scholar] [CrossRef] 
[53] Zang, X., Monge, M.E., McCarty, N.A., et al. (2017) Feasibility of Early Detection of Cystic Fibrosis Acute Pulmonary Exacerbations by Exhaled Breath Condensate Metabolomics: A Pilot Study. Journal of Proteome Research, 16, 550-558. [Google Scholar] [CrossRef] [PubMed]
[54] Zang, X., Monge, M.E., Gaul, D.A., et al. (2020) Early Detection of Cystic Fibrosis Acute Pulmonary Exacerbations by Exhaled Breath Condensate Metabolomics. Journal of Proteome Research, 19, 144-152. [Google Scholar] [CrossRef] [PubMed]

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