Advertisement

Application of metabolomics in autoimmune diseases: Insight into biomarkers and pathology

      Highlights

      • Metabolic profiling is extremely useful for identifying biomarkers.
      • Metabolic profiling discriminates between autoimmune diseases and healthy subjects.
      • Biomarkers identified in autoimmune diseases involve many pathways.
      • The well-established technique for metabolomics includes NMR and MS.

      Abstract

      Metabolomics has recently become a new technology using mass spectrometry (MS) and high-resolution proton nuclear magnetic resonance (NMR) to access metabolite profiles in biofluids or tissue extracts for the detection of biomarker molecules and biochemical effects induced by a disease or its therapeutic intervention. This review outlines recent advances in the use of metabolomic techniques to study autoimmune diseases (ADs), including multiple sclerosis (MS), rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), autoimmune diabetes et al. Many studies have demonstrated that AD patients including subtypes of some diseases, and healthy individuals can be distinguished using metabolic profiling accompanied with well-established data analysis tools including principal component analysis (PCA) and partial least squares (PLS). These metabolites not only affect glucose, amino acid and lipid metabolism, but also involve alteration of neurotransmitters, nucleotides, immune responses and anti-inflammatory responses. Knowledge of unique metabolomic fingerprint in ADs could be useful for diagnosis, treatment, and detection mechanisms of diseases.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Neuroimmunology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Aasly J.
        • Garseth M.
        • Sonnewald U.
        • Zwart J.A.
        • White L.R.
        • Unsgard G.
        Cerebrospinal fluid lactate and glutamine are reduced in multiple sclerosis.
        Acta Neurol. Scand. 1997; 95: 9-12
        • Abdalmula A.
        • Washington E.A.
        • House J.V.
        • Dooley L.M.
        • Blacklaws B.A.
        • Ghosh P.
        • et al.
        Clinical and histopathological characterization of a large animal (ovine) model of collagen-induced arthritis.
        Vet. Immunol. Immunopathol. 2014; 159: 83-90
        • Aprea E.
        • Cappellin L.
        • Gasperi F.
        • Morisco F.
        • Lembo V.
        • Rispo A.
        • et al.
        Application of PTR–TOF–MS to investigate metabolites in exhaled breath of patients affected by coeliac disease under gluten free diet.
        J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2014; 966: 208-213
        • Bakshi R.
        • Neema M.
        • Healy B.C.
        • Liptak Z.
        • Betensky R.A.
        • Buckle G.J.
        • et al.
        Predicting clinical progression in multiple sclerosis with the magnetic resonance disease severity scale.
        Arch. Neurol. 2008; 65: 1449-1453
        • Bernini P.
        • Bertini I.
        • Calabro A.
        • la Marca G.
        • Lami G.
        • Luchinat C.
        • et al.
        Are patients with potential celiac disease really potential? The answer of metabonomics.
        J. Proteome Res. 2011; 10: 714-721
        • Bertini I.
        • Calabro A.
        • De Carli V.
        • Luchinat C.
        • Nepi S.
        • Porfirio B.
        • et al.
        The metabonomic signature of celiac disease.
        J. Proteome Res. 2009; 8: 170-177
        • Bradford C.M.
        • Ramos I.
        • Cross A.K.
        • Haddock G.
        • McQuaid S.
        • Nicholas A.P.
        • et al.
        Localisation of citrullinated proteins in normal appearing white matter and lesions in the central nervous system in multiple sclerosis.
        J. Neuroimmunol. 2014; 273: 85-95
        • Brugnara L.
        • Vinaixa M.
        • Murillo S.
        • Samino S.
        • Rodriguez M.A.
        • Beltran A.
        • et al.
        Metabolomics approach for analyzing the effects of exercise in subjects with type 1 diabetes mellitus.
        PLoS One. 2012; 7: e40600
        • Dawiskiba T.
        • Deja S.
        • Mulak A.
        • Zabek A.
        • Jawien E.
        • Pawelka D.
        • et al.
        Serum and urine metabolomic fingerprinting in diagnostics of inflammatory bowel diseases.
        World J. Gastroenterol. 2014; 20: 163-174
        • de Grauw J.C.
        • van de Lest C.H.
        • van Weeren P.R.
        A targeted lipidomics approach to the study of eicosanoid release in synovial joints.
        Arthritis Res. Ther. 2011; 13: R123
        • de Seze J.
        • Lebrun C.
        • Stojkovic T.
        • Ferriby D.
        • Chatel M.
        • Vermersch P.
        Is Devic's neuromyelitis optica a separate disease? A comparative study with multiple sclerosis.
        Mult. Scler. 2003; 9: 521-525
        • Dieme B.
        • Halimi J.M.
        • Emond P.
        • Buchler M.
        • Nadal-Desbarat L.
        • Blasco H.
        • et al.
        Assessing the metabolic effects of calcineurin inhibitors in renal transplant recipients by urine metabolic profiling.
        Transplantation. 2014; 98: 195-201
        • Ding X.
        • Hu J.
        • Li J.
        • Zhang Y.
        • Shui B.
        • Ding Z.
        • et al.
        Metabolomics analysis of collagen-induced arthritis in rats and interventional effects of oral tolerance.
        Anal. Biochem. 2014; 458: 49-57
        • Dong F.
        • Zhang L.
        • Hao F.
        • Tang H.
        • Wang Y.
        Systemic responses of mice to dextran sulfate sodium-induced acute ulcerative colitis using 1H NMR spectroscopy.
        J. Proteome Res. 2013; 12: 2958-2966
        • Dutta T.
        • Chai H.S.
        • Ward L.E.
        • Ghosh A.
        • Persson X.M.
        • Ford G.C.
        • et al.
        Concordance of changes in metabolic pathways based on plasma metabolomics and skeletal muscle transcriptomics in type 1 diabetes.
        Diabetes. 2012; 61: 1004-1016
        • Fathi F.
        • Ektefa F.
        • Arefi Oskouie A.
        • Rostami K.
        • Rezaei-Tavirani M.
        • Mohammad Alizadeh A.H.
        • et al.
        NMR based metabonomics study on celiac disease in the blood serum.
        Gastroenterol. Hepatol. Bed Bench. 2013; 6: 190-194
        • Fathi F.
        • Oskouie A.A.
        • Tafazzoli M.
        • Naderi N.
        • Sohrabzedeh K.
        • Fathi S.
        • et al.
        Metabonomics based NMR in Crohn's disease applying PLS-DA.
        Gastroenterol. Hepatol. Bed Bench. 2013; 6: S82-S86
        • Giera M.
        • Ioan-Facsinay A.
        • Toes R.
        • Gao F.
        • Dalli J.
        • Deelder A.M.
        • et al.
        Lipid and lipid mediator profiling of human synovial fluid in rheumatoid arthritis patients by means of LC–MS/MS.
        Biochim. Biophys. Acta. 2012; 1821: 1415-1424
        • Gu Y.
        • Lu C.
        • Zha Q.
        • Kong H.
        • Lu X.
        • Lu A.
        • et al.
        Plasma metabonomics study of rheumatoid arthritis and its Chinese medicine subtypes by using liquid chromatography and gas chromatography coupled with mass spectrometry.
        Mol. Biosyst. 2012; 8: 1535-1543
        • Haskell W.L.
        • Lee I.M.
        • Pate R.R.
        • Powell K.E.
        • Blair S.N.
        • Franklin B.A.
        • et al.
        Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association.
        Med. Sci. Sports Exerc. 2007; 39: 1423-1434
        • Hong Y.S.
        • Ahn Y.T.
        • Park J.C.
        • Lee J.H.
        • Lee H.
        • Huh C.S.
        • et al.
        1H NMR-based metabonomic assessment of probiotic effects in a colitis mouse model.
        Arch. Pharm. Res. 2010; 33: 1091-1101
        • Hosch W.
        • Junghanss T.
        • Stojkovic M.
        • Brunetti E.
        • Heye T.
        • Kauffmann G.W.
        • et al.
        Metabolic viability assessment of cystic echinococcosis using high-field 1H MRS of cyst contents.
        NMR Biomed. 2008; 21: 734-754
        • Jansson J.
        • Willing B.
        • Lucio M.
        • Fekete A.
        • Dicksved J.
        • Halfvarson J.
        • et al.
        Metabolomics reveals metabolic biomarkers of Crohn's disease.
        PLoS One. 2009; 4: e6386
        • Kapoor S.R.
        • Filer A.
        • Fitzpatrick M.A.
        • Fisher B.A.
        • Taylor P.C.
        • Buckley C.D.
        • et al.
        Metabolic profiling predicts response to anti-tumor necrosis factor alpha therapy in patients with rheumatoid arthritis.
        Arthritis Rheum. 2013; 65: 1448-1456
        • Kim O.Y.
        • Lee J.H.
        • Sweeney G.
        Metabolomic profiling as a useful tool for diagnosis and treatment of chronic disease: focus on obesity, diabetes and cardiovascular diseases.
        Expert. Rev. Cardiovasc. Ther. 2013; 11: 61-68
        • Kirov I.I.
        • Tal A.
        • Babb J.S.
        • Herbert J.
        • Gonen O.
        Serial proton MR spectroscopy of gray and white matter in relapsing–remitting MS.
        Neurology. 2013; 80: 39-46
        • Kriegsmann M.
        • Seeley E.H.
        • Schwarting A.
        • Kriegsmann J.
        • Otto M.
        • Thabe H.
        • et al.
        MALDI MS imaging as a powerful tool for investigating synovial tissue.
        Scand. J. Rheumatol. 2012; 41: 305-309
        • Kumar V.
        • Dwivedi D.K.
        • Jagannathan N.R.
        High-resolution NMR spectroscopy of human body fluids and tissues in relation to prostate cancer.
        NMR Biomed. 2014; 27: 80-89
        • Lauridsen M.B.
        • Bliddal H.
        • Christensen R.
        • Danneskiold-Samsoe B.
        • Bennett R.
        • Keun H.
        • et al.
        1H NMR spectroscopy-based interventional metabolic phenotyping: a cohort study of rheumatoid arthritis patients.
        J. Proteome Res. 2010; 9: 4545-4553
        • Leung T.F.
        • Ko F.W.
        • Wong G.W.
        Recent advances in asthma biomarker research.
        Ther. Adv. Respir. Dis. 2013; 7: 297-308
        • Lista S.
        • Zetterberg H.
        • Dubois B.
        • Blennow K.
        • Hampel H.
        Cerebrospinal fluid analysis in Alzheimer's disease: technical issues and future developments.
        J. Neurol. 2014; 261: 1234-1243
        • Lu K.
        • Knutson C.G.
        • Wishnok J.S.
        • Fox J.G.
        • Tannenbaum S.R.
        Serum metabolomics in a Helicobacter hepaticus mouse model of inflammatory bowel disease reveal important changes in the microbiome, serum peptides, and intermediary metabolism.
        J. Proteome Res. 2012; 11: 4916-4926
        • Lutz N.W.
        • Viola A.
        • Malikova I.
        • Confort-Gouny S.
        • Audoin B.
        • Ranjeva J.P.
        • et al.
        Inflammatory multiple-sclerosis plaques generate characteristic metabolic profiles in cerebrospinal fluid.
        PLoS One. 2007; 2: e595
        • Lynch J.
        • Peeling J.
        • Auty A.
        • Sutherland G.R.
        Nuclear magnetic resonance study of cerebrospinal fluid from patients with multiple sclerosis.
        Can. J. Neurol. Sci. 1993; 20: 194-198
        • Madsen R.K.
        • Lundstedt T.
        • Gabrielsson J.
        • Sennbro C.J.
        • Alenius G.M.
        • Moritz T.
        • et al.
        Diagnostic properties of metabolic perturbations in rheumatoid arthritis.
        Arthritis Res. Ther. 2011; 13: R19
        • Makinen V.P.
        • Soininen P.
        • Forsblom C.
        • Parkkonen M.
        • Ingman P.
        • Kaski K.
        • et al.
        Diagnosing diabetic nephropathy by 1H NMR metabonomics of serum.
        MAGMA. 2006; 19: 281-296
        • Mangalam A.
        • Poisson L.
        • Nemutlu E.
        • Datta I.
        • Denic A.
        • Dzeja P.
        • et al.
        Profile of circulatory metabolites in a relapsing–remitting animal model of multiple sclerosis using global metabolomics.
        J. Clin. Cell. Immunol. 2013; 4
        • Martinez-Pinna R.
        • Barbas C.
        • Blanco-Colio L.M.
        • Tunon J.
        • Ramos-Mozo P.
        • Lopez J.A.
        • et al.
        Proteomic and metabolomic profiles in atherothrombotic vascular disease.
        Curr. Atheroscler. Rep. 2010; 12: 202-208
        • Mehrpour M.
        • Kyani A.
        • Tafazzoli M.
        • Fathi F.
        • Joghataie M.T.
        A metabonomics investigation of multiple sclerosis by nuclear magnetic resonance.
        Magn. Reson. Chem. 2013; 51: 102-109
        • Menni C.
        • Fauman E.
        • Erte I.
        • Perry J.R.
        • Kastenmuller G.
        • Shin S.Y.
        • et al.
        Biomarkers for type 2 diabetes and impaired fasting glucose using a nontargeted metabolomics approach.
        Diabetes. 2013; 62: 4270-4276
        • Menon R.
        • Jones J.
        • Gunst P.R.
        • Kacerovsky M.
        • Fortunato S.J.
        • Saade G.R.
        • et al.
        Amniotic fluid metabolomic analysis in spontaneous preterm birth.
        Reprod. Sci. 2014; 21: 791-803
        • Mohanty S.T.
        • Kottam L.
        • Gambardella A.
        • Nicklin M.J.
        • Coulton L.
        • Hughes D.
        • et al.
        Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis.
        Arthritis Res. Ther. 2010; 12: R149
        • Moussallieh F.M.
        • Elbayed K.
        • Chanson J.B.
        • Rudolf G.
        • Piotto M.
        • De Seze J.
        • et al.
        Serum analysis by 1H nuclear magnetic resonance spectroscopy: a new tool for distinguishing neuromyelitis optica from multiple sclerosis.
        Mult. Scler. 2014; 20: 558-565
        • Nagana Gowda G.A.
        • Shanaiah N.
        • Cooper A.
        • Maluccio M.
        • Raftery D.
        Bile acids conjugation in human bile is not random: new insights from (1)H-NMR spectroscopy at 800 MHz.
        Lipids. 2009; 44: 527-535
        • Naz S.
        • Vallejo M.
        • Garcia A.
        • Barbas C.
        Method validation strategies involved in non-targeted metabolomics.
        J. Chromatogr. A. 2014; 1353: 99-105
        • Nicoli F.
        • Vion-Dury J.
        • Confort-Gouny S.
        • Maillet S.
        • Gastaut J.L.
        • Cozzone P.J.
        Cerebrospinal fluid metabolic profiles in multiple sclerosis and degenerative dementias obtained by high resolution proton magnetic resonance spectroscopy.
        C. R. Acad. Sci. III. 1996; 319: 623-631
        • Noga M.J.
        • Dane A.
        • Shi S.
        • Attali A.
        • van Aken H.
        • Suidgeest E.
        • et al.
        Metabolomics of cerebrospinal fluid reveals changes in the central nervous system metabolism in a rat model of multiple sclerosis.
        Metabolomics. 2012; 8: 253-263
        • Ouyang X.
        • Dai Y.
        • Wen J.L.
        • Wang L.X.
        (1)H NMR-based metabolomic study of metabolic profiling for systemic lupus erythematosus.
        Lupus. 2011; 20: 1411-1420
        • Pillai S.
        Rethinking mechanisms of autoimmune pathogenesis.
        J. Autoimmun. 2013; 45: 97-103
        • Qi X.
        • Zhang Y.
        • Gao J.
        • Chen T.
        • Zhao A.
        • Yan Y.
        • et al.
        Metabolite profiling of hemodialysate using gas chromatography time-of-flight mass spectrometry.
        J. Pharm. Biomed. Anal. 2011; 55: 1142-1147
        • Regenold W.T.
        • Phatak P.
        • Makley M.J.
        • Stone R.D.
        • Kling M.A.
        Cerebrospinal fluid evidence of increased extra-mitochondrial glucose metabolism implicates mitochondrial dysfunction in multiple sclerosis disease progression.
        J. Neurol. Sci. 2008; 275: 106-112
        • Reinke S.
        • Broadhurst D.
        • Sykes B.
        • Baker G.
        • Catz I.
        • Warren K.
        • et al.
        Metabolomic profiling in multiple sclerosis: insights into biomarkers and pathogenesis.
        Mult. Scler. 2014; 20: 1396-1400
        • Rezaei-Tavirani M.
        • Fathi F.
        • Darvizeh F.
        • Zali M.R.
        • Rostami Nejad M.
        • Rostami K.
        • et al.
        Advantage of applying OSC to (1)H NMR-based metabonomic data of celiac disease.
        Int. J. Endocrinol. Metab. 2012; 10: 548-552
        • Rist M.J.
        • Muhle-Goll C.
        • Gorling B.
        • Bub A.
        • Heissler S.
        • Watzl B.
        • et al.
        Influence of freezing and storage procedure on human urine samples in NMR-based metabolomics.
        Metabolites. 2013; 3: 243-258
        • Santone C.
        • Dinallo V.
        • Paci M.
        • D'Ottavio S.
        • Barbato G.
        • Bernardini S.
        Saliva metabolomics by NMR for the evaluation of sport performance.
        J. Pharm. Biomed. Anal. 2014; 88: 441-446
        • Schicho R.
        • Shaykhutdinov R.
        • Ngo J.
        • Nazyrova A.
        • Schneider C.
        • Panaccione R.
        • et al.
        Quantitative metabolomic profiling of serum, plasma, and urine by (1)H NMR spectroscopy discriminates between patients with inflammatory bowel disease and healthy individuals.
        J. Proteome Res. 2012; 11: 3344-3357
        • Schmidt C.W.
        Questions persist: environmental factors in autoimmune disease.
        Environ. Health Perspect. 2011; 119: A249-A253
        • Schoffel N.
        • Mache S.
        • Quarcoo D.
        • Scutaru C.
        • Vitzthum K.
        • Groneberg D.A.
        • et al.
        Rheumatoid arthritis: scientific development from a critical point of view.
        Rheumatol. Int. 2010; 30: 505-513
        • Sellitto M.
        • Bai G.
        • Serena G.
        • Fricke W.F.
        • Sturgeon C.
        • Gajer P.
        • et al.
        Proof of concept of microbiome–metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants.
        PLoS One. 2012; 7: e33387
        • Simone I.L.
        • Federico F.
        • Trojano M.
        • Tortorella C.
        • Liguori M.
        • Giannini P.
        • et al.
        High resolution proton MR spectroscopy of cerebrospinal fluid in MS patients. Comparison with biochemical changes in demyelinating plaques.
        J. Neurol. Sci. 1996; 144: 182-190
        • Sinclair A.J.
        • Viant M.R.
        • Ball A.K.
        • Burdon M.A.
        • Walker E.A.
        • Stewart P.M.
        • et al.
        NMR-based metabolomic analysis of cerebrospinal fluid and serum in neurological diseases—a diagnostic tool?.
        NMR Biomed. 2010; 23: 123-132
        • Smolinska A.
        • Attali A.
        • Blanchet L.
        • Ampt K.
        • Tuinstra T.
        • van Aken H.
        • et al.
        NMR and pattern recognition can distinguish neuroinflammation and peripheral inflammation.
        J. Proteome Res. 2011; 10: 4428-4438
        • Surolia I.
        • Pirnie S.P.
        • Chellappa V.
        • Taylor K.N.
        • Cariappa A.
        • Moya J.
        • et al.
        Functionally defective germline variants of sialic acid acetylesterase in autoimmunity.
        Nature. 2010; 466: 243-247
        • Tao M.
        • Xiu D.R.
        Metabonomic analysis of rats with acute heart rejection.
        Transplant. Proc. 2013; 45: 618-624
        • Tso V.K.
        • Sydora B.C.
        • Foshaug R.R.
        • Churchill T.A.
        • Doyle J.
        • Slupsky C.M.
        • et al.
        Metabolomic profiles are gender, disease and time specific in the interleukin-10 gene-deficient mouse model of inflammatory bowel disease.
        PLoS One. 2013; 8: e67654
        • van Belle T.L.
        • Coppieters K.T.
        • von Herrath M.G.
        Type 1 diabetes: etiology, immunology, and therapeutic strategies.
        Physiol. Rev. 2011; 91: 79-118
        • van Wietmarschen H.A.
        • Dai W.
        • van der Kooij A.J.
        • Reijmers T.H.
        • Schroen Y.
        • Wang M.
        • et al.
        Characterization of rheumatoid arthritis subtypes using symptom profiles, clinical chemistry and metabolomics measurements.
        PLoS One. 2012; 7: e44331
        • Vingara L.K.
        • Yu H.J.
        • Wagshul M.E.
        • Serafin D.
        • Christodoulou C.
        • Pelczer I.
        • et al.
        Metabolomic approach to human brain spectroscopy identifies associations between clinical features and the frontal lobe metabolome in multiple sclerosis.
        Neuroimage. 2013; 82: 586-594
        • Walker A.
        • Lucio M.
        • Pfitzner B.
        • Scheerer M.F.
        • Neschen S.
        • Hrabe de Angelis M.
        • et al.
        The importance of sulfur-containing metabolites in discriminating fecal extracts between normal and type 2 diabetic mice.
        J. Proteome Res. 2014; 13: 4220-4231
        • Wallin M.T.
        • Page W.F.
        • Kurtzke J.F.
        Epidemiology of multiple sclerosis in US veterans. VIII. Long-term survival after onset of multiple sclerosis.
        Brain. 2000; 123: 1677-1687
        • Wang Z.
        • Chen Z.
        • Yang S.
        • Wang Y.
        • Yu L.
        • Zhang B.
        • et al.
        (1)H NMR-based metabolomic analysis for identifying serum biomarkers to evaluate methotrexate treatment in patients with early rheumatoid arthritis.
        Exp. Ther. Med. 2012; 4: 165-171
        • Wang J.B.
        • Pu S.B.
        • Sun Y.
        • Li Z.F.
        • Niu M.
        • Yan X.Z.
        • et al.
        Metabolomic profiling of autoimmune hepatitis: the diagnostic utility of nuclear magnetic resonance spectroscopy.
        J. Proteome Res. 2014; 13: 3792-3801
        • Weljie A.M.
        • Dowlatabadi R.
        • Miller B.J.
        • Vogel H.J.
        • Jirik F.R.
        An inflammatory arthritis-associated metabolite biomarker pattern revealed by 1H NMR spectroscopy.
        J. Proteome Res. 2007; 6: 3456-3464
        • Wu H.
        • Southam A.D.
        • Hines A.
        • Viant M.R.
        High-throughput tissue extraction protocol for NMR- and MS-based metabolomics.
        Anal. Biochem. 2008; 372: 204-212
        • Wu T.
        • Xie C.
        • Han J.
        • Ye Y.
        • Weiel J.
        • Li Q.
        • et al.
        Metabolic disturbances associated with systemic lupus erythematosus.
        PLoS One. 2012; 7: e37210
        • Xu F.
        • Tavintharan S.
        • Sum C.F.
        • Woon K.
        • Lim S.C.
        • Ong C.N.
        Metabolic signature shift in type 2 diabetes mellitus revealed by mass spectrometry-based metabolomics.
        J. Clin. Endocrinol. Metab. 2013; 98: E1060-E1065
        • Yang H.
        • Li Y.
        • Wu W.
        • Sun Q.
        • Zhang Y.
        • Zhao W.
        • et al.
        The incidence of inflammatory bowel disease in northern china: a prospective population-based study.
        PLoS One. 2014; 9: e101296
        • Young S.P.
        • Kapoor S.R.
        • Viant M.R.
        • Byrne J.J.
        • Filer A.
        • Buckley C.D.
        • et al.
        The impact of inflammation on metabolomic profiles in patients with arthritis.
        Arthritis Rheum. 2013; 65: 2015-2023
        • Zenobi R.
        Single-cell metabolomics: analytical and biological perspectives.
        Science. 2013; 342: 1243259
        • Zhang X.
        • Choi F.F.
        • Zhou Y.
        • Leung F.P.
        • Tan S.
        • Lin S.
        • et al.
        Metabolite profiling of plasma and urine from rats with TNBS-induced acute colitis using UPLC–ESI–QTOF–MS-based metabonomics—a pilot study.
        FEBS J. 2012; 279: 2322-2338
        • Zhang Y.
        • Lin L.
        • Xu Y.
        • Lin Y.
        • Jin Y.
        • Zheng C.
        1H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis.
        Biochem. Biophys. Res. Commun. 2013; 433: 547-551
        • Zhang A.H.
        • Sun H.
        • Yan G.L.
        • Yuan Y.
        • Han Y.
        • Wang X.J.
        Metabolomics study of type 2 diabetes using ultra-performance LC–ESI/quadrupole-TOF high-definition MS coupled with pattern recognition methods.
        J. Physiol. Biochem. 2014; 70: 117-128
        • Zhang H.
        • Fu P.
        • Ke B.
        • Wang S.
        • Li M.
        • Han L.
        • et al.
        Metabolomic analysis of biochemical changes in the plasma and urine of collagen-induced arthritis in rats after treatment with Huang-Lian-Jie-Du-Tang.
        J. Ethnopharmacol. 2014; 154: 55-64