{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T05:20:36Z","timestamp":1778822436986,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T00:00:00Z","timestamp":1540252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009888","name":"Region of Tuscany","doi-asserted-by":"publisher","award":["Ricerca di marcatori precoci di ischemia intestinale: MaPi-Int"],"award-info":[{"award-number":["Ricerca di marcatori precoci di ischemia intestinale: MaPi-Int"]}],"id":[{"id":"10.13039\/501100009888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Precision medicine may significantly contribute to rapid disease diagnosis and targeted therapy, but relies on the availability of detailed, subject specific, clinical information. Proton nuclear magnetic resonance (1H\u2013NMR) spectroscopy of body fluids can extract individual metabolic fingerprints. Herein, we studied 64 patients admitted to the Florence main hospital emergency room with severe abdominal pain. A blood sample was drawn from each patient at admission, and the corresponding sera underwent 1H\u2013NMR metabolomics fingerprinting. Unsupervised Principal Component Analysis (PCA) analysis showed a significant discrimination between a group of patients with symptoms of upper abdominal pain and a second group consisting of patients with diffuse abdominal\/intestinal pain. Prompted by this observation, supervised statistical analysis (Orthogonal Partial Least Squares\u2013Discriminant Analysis (OPLS-DA)) showed a very good discrimination (&gt;90%) between the two groups of symptoms. This is a surprising finding, given that neither of the two symptoms points directly to a specific disease among those studied here. Actually herein, upper abdominal pain may result from either symptomatic gallstones, cholecystitis, or pancreatitis, while diffuse abdominal\/intestinal pain may result from either intestinal ischemia, strangulated obstruction, or mechanical obstruction. Although limited by the small number of samples from each of these six conditions, discrimination of these diseases was attempted. In the first symptom group, &gt;70% discrimination accuracy was obtained among symptomatic gallstones, pancreatitis, and cholecystitis, while for the second symptom group &gt;85% classification accuracy was obtained for intestinal ischemia, strangulated obstruction, and mechanical obstruction. No single metabolite stands up as a possible biomarker for any of these diseases, while the contribution of the whole 1H\u2013NMR serum fingerprint seems to be a promising candidate, to be confirmed on larger cohorts, as a first-line discriminator for these diseases.<\/jats:p>","DOI":"10.3390\/ijms19113288","type":"journal-article","created":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T02:59:40Z","timestamp":1540349980000},"page":"3288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Fingerprinting Acute Digestive Diseases by Untargeted NMR Based Metabolomics"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7224-0412","authenticated-orcid":false,"given":"Panteleimon G.","family":"Takis","sequence":"first","affiliation":[{"name":"Giotto Biotech, S.r.l, Via Madonna del Piano 6, 50019 Sesto Fiorentino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2963-4085","authenticated-orcid":false,"given":"Antonio","family":"Taddei","sequence":"additional","affiliation":[{"name":"Department of Surgery and Translational Medicine, School of Medicine, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7940-7908","authenticated-orcid":false,"given":"Riccardo","family":"Pini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Grifoni","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine and Surgery, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Tarantini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Bechi","sequence":"additional","affiliation":[{"name":"Department of Surgery and Translational Medicine, School of Medicine, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Luchinat","sequence":"additional","affiliation":[{"name":"Giotto Biotech, S.r.l, Via Madonna del Piano 6, 50019 Sesto Fiorentino, Italy"},{"name":"Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/nrgastro.2012.100","article-title":"What is personalized medicine and what should it replace?","volume":"9","author":"Whitcomb","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/nrd4759","article-title":"Market watch: Where is personalized medicine in industry heading?","volume":"12","author":"Milne","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.tibtech.2014.08.003","article-title":"Taking your breath away: Metabolomics breathes life in to personalized medicine","volume":"32","author":"Rattray","year":"2014","journal-title":"Trends Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Psychogios, N., Hau, D.D., Peng, J., Guo, A.C., Mandal, R., Bouatra, S., Sinelnikov, I., Krishnamurthy, R., Eisner, R., and Gautam, B. (2011). The human serum metabolome. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016957"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-017-01587-0","article-title":"Deconvoluting interrelationships between concentrations and chemical shifts in urine provides a powerful analysis tool","volume":"8","author":"Takis","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev.anchem.1.031207.113026","article-title":"Spectroscopic and Statistical Techniques for Information Recovery in Metabonomics and Metabolomics","volume":"1","author":"Lindon","year":"2008","journal-title":"Annu. Rev. Anal. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1053\/j.gastro.2015.07.003","article-title":"Biomarkers of Inflammation in Inflammatory Bowel Disease","volume":"149","author":"Sands","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1021\/pr9008223","article-title":"Metabonomics in ulcerative colitis: Diagnostics, biomarker identification, and insight into the pathophysiology","volume":"9","author":"Bjerrum","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1586\/egh.12.1","article-title":"Biofluid metabolomics using 1H NMR spectroscopy: The road to biomarker discovery in gastroenterology and hepatology","volume":"6","author":"Patel","year":"2012","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"W551","DOI":"10.2214\/AJR.10.4341","article-title":"Imaging of Biliary Tract Disease","volume":"197","author":"Maher","year":"2011","journal-title":"Am. J. Roentgenol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S0140-6736(78)92543-6","article-title":"Endoscopic treatment of biliary-tract diseases: An International Study","volume":"312","author":"Safrany","year":"1978","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1002\/bjs.1800781007","article-title":"Risk of strangulation in groin hernias","volume":"78","author":"Gallegos","year":"1991","journal-title":"Br. J. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S0039-6060(97)90363-9","article-title":"Human intestinal fatty acid binding protein: Report of an assay with studies in normal volunteers and intestinal ischemia","volume":"121","author":"Lieberman","year":"1997","journal-title":"Surgery"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1136\/gutjnl-2012-304176","article-title":"Intestinal inflammation in postoperative ileus: Pathogenesis and therapeutic targets","volume":"62","author":"Rychter","year":"2013","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1097\/SLA.0b013e318207a767","article-title":"Early Diagnosis of Intestinal Ischemia Using Urinary and Plasma Fatty Acid Binding Proteins","volume":"253","author":"Thuijls","year":"2011","journal-title":"Ann. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1586\/17474124.2014.945912","article-title":"Colorectal cancer: The potential of metabolic fingerprinting","volume":"8","author":"Turano","year":"2014","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"34371","DOI":"10.1038\/srep34371","article-title":"Accuracy of the serum intestinal fatty-acid-binding protein for diagnosis of acute intestinal ischemia: A meta-analysis","volume":"6","author":"Sun","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/BF01887331","article-title":"Computed tomography as an adjunct to ultrasound in the diagnosis of acute acalculous cholecystitis","volume":"16","author":"Blankenberg","year":"1991","journal-title":"Gastrointest. Radiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/ncpgasthep0390","article-title":"Biliary sludge and acute pancreatitis during pregnancy","volume":"3","author":"Ko","year":"2006","journal-title":"Nat. Clin. Pract. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cgh.2009.10.017","article-title":"Nuclear Medicine Hepatobiliary Imaging","volume":"8","author":"Ziessman","year":"2010","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1148\/radiology.148.1.6856839","article-title":"Gangrenous cholecystitis: Diagnosis by ultrasound","volume":"148","author":"Jeffrey","year":"1983","journal-title":"Radiology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Oderich, G.S. (2015). Noninvasive Arterial Imaging: Computed Tomography and Magnetic Resonance Angiography. Mesenteric Vascular Disease, Springer.","DOI":"10.1007\/978-1-4939-1847-8"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1158\/0008-5472.CAN-11-1543","article-title":"Metabolomic NMR Fingerprinting to Identify and Predict Survival of Patients with Metastatic Colorectal Cancer","volume":"72","author":"Bertini","year":"2012","journal-title":"Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1159\/000055816","article-title":"Serum Free Fatty Acid Concentration in Patients with Acute Pancreatitis","volume":"1","author":"Sztefko","year":"2001","journal-title":"Pancreatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/hep.1840110402","article-title":"Isolation of a potent cholesterol nucleation-promoting activity from human gallbladder bile: Role in the pathogenesis of gallstone disease","volume":"11","author":"Groen","year":"1990","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1007\/BF01296004","article-title":"Intestinal fatty acid-binding protein as a sensitive marker of intestinal ischemia","volume":"37","author":"Kanda","year":"1992","journal-title":"Dig. Dis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/0002-9610(94)90101-5","article-title":"Serum D(\u2212)-lactate levels as an aid to diagnosing acute intestinal ischemia","volume":"167","author":"Murray","year":"2015","journal-title":"Am. J. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kittaka, H., Akimoto, H., Takeshita, H., Funaoka, H., Hazui, H., Okamoto, M., Kobata, H., and Ohishi, Y. (2014). Usefulness of intestinal fatty acid-binding protein in predicting strangulated small bowel obstruction. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099915"},{"key":"ref_29","first-page":"181","article-title":"An overview of lipid abnormalities in patients with inflammatory bowel disease","volume":"24","author":"Agouridis","year":"2011","journal-title":"Ann. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1007\/s00268-009-0074-7","article-title":"Systematic Review and Pooled Estimates for the Diagnostic Accuracy of Serological Markers for Intestinal Ischemia","volume":"33","author":"Evennett","year":"2009","journal-title":"World J. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.bbadis.2005.12.006","article-title":"Alterations in intestinal fatty acid metabolism in inflammatory bowel disease","volume":"1762","author":"Heimerl","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"97","DOI":"10.4292\/wjgpt.v4.i4.97","article-title":"Metabolomics as a diagnostic tool in gastroenterology","volume":"4","author":"Verbeke","year":"2013","journal-title":"World J. Gastrointest. Pharmacol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/d41586-017-07522-z","article-title":"Five ways to fix statistics","volume":"551","author":"Leek","year":"2017","journal-title":"Nature"},{"key":"ref_34","first-page":"92","article-title":"Multivariate Analysis in Metabolomics","volume":"1","author":"Worley","year":"2013","journal-title":"Curr. Metabolomics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/cem.833","article-title":"Non-parametric statistical methods for multivariate calibration model selection and comparison","volume":"17","author":"Thomas","year":"2004","journal-title":"J. Chemom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0169-7439(94)85050-X","article-title":"Comparing the predictive accuracy of models using a simple randomization test","volume":"25","year":"1994","journal-title":"Chemom. Intell. Lab. Syst."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4104","DOI":"10.1039\/C6FO00560H","article-title":"1H-NMR based metabolomics study for the detection of the human urine metabolic profile effects of Origanum Dictamnus tea ingestion","volume":"7","author":"Takis","year":"2016","journal-title":"Food Funct."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lindon, J.C. (2010). Biofluids Studied by NMR. Encyclopedia of Spectroscopy and Spectrometry, Academic Press. [2nd ed.].","DOI":"10.1016\/B978-0-12-374413-5.00376-6"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.bbrc.2008.08.007","article-title":"Disease","volume":"375","author":"Tukiainen","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"D521","DOI":"10.1093\/nar\/gkl923","article-title":"HMDB: The Human Metabolome Database","volume":"35","author":"Wishart","year":"2007","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/11\/3288\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:25:35Z","timestamp":1760196335000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/11\/3288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,23]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,11]]}},"alternative-id":["ijms19113288"],"URL":"https:\/\/doi.org\/10.3390\/ijms19113288","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,23]]}}}