{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:33:57Z","timestamp":1790534037993,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T00:00:00Z","timestamp":1649894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AGENCE NATIONALE DE LA RECHERCHE (ANR)","award":["ANR-15-CE14-0013-01"],"award-info":[{"award-number":["ANR-15-CE14-0013-01"]}]},{"name":"FONDATION DE COOPERATION SCIENTIFIQUE CAMPUS PARIS-SACLAY","award":["2016-1212I"],"award-info":[{"award-number":["2016-1212I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Thanks to the latest developments in mass spectrometry, software and standards, metaproteomics is emerging as the vital complement of metagenomics, to make headway in understanding the actual functioning of living and active microbial communities. Modern metaproteomics offers new possibilities in the area of clinical diagnosis. This is illustrated here, for the still highly challenging diagnosis of intestinal bowel diseases (IBDs). Using bottom-up proteomics, we analyzed the gut metaproteomes of the same twenty faecal specimens processed either fresh or after a two-month freezing period. We focused on metaproteomes of microbial cell envelopes since it is an outstanding way of capturing host and host\u2013microbe interaction signals. The protein profiles of pairs of fresh and frozen-thawed samples were closely related, making feasible deferred analysis in a distant diagnosis centre. The taxonomic and functional landscape of microbes in diverse IBD phenotypes\u2014active ulcerative colitis, or active Crohn\u2019s disease either with ileo-colonic or exclusive colonic localization\u2014differed from each other and from the controls. Based on their specific peptides, we could identify proteins that were either strictly overrepresented or underrepresented in all samples of one clinical group compared to all samples of another group, paving the road for promising additional diagnostic tool for IBDs.<\/jats:p>","DOI":"10.3390\/cells11081340","type":"journal-article","created":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T21:44:06Z","timestamp":1649972646000},"page":"1340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Modern Metaproteomics: A Unique Tool to Characterize the Active Microbiome in Health and Diseases, and Pave the Road towards New Biomarkers\u2014Example of Crohn\u2019s Disease and Ulcerative Colitis Flare-Ups"],"prefix":"10.3390","volume":"11","author":[{"given":"C\u00e9line","family":"Henry","sequence":"first","affiliation":[{"name":"PAPPSO, Micalis Institute, INRAE, AgroParisTech, Universit\u00e9 Paris-Saclay, 78350 Jouy-en-Josas, France"},{"name":"Micalis Institute, INRAE, AgroParisTech, Universit\u00e9 Paris-Saclay, 78350 Jouy-en-Josas, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6267-4519","authenticated-orcid":false,"given":"Ariane","family":"Bassignani","sequence":"additional","affiliation":[{"name":"PAPPSO, Micalis Institute, INRAE, AgroParisTech, Universit\u00e9 Paris-Saclay, 78350 Jouy-en-Josas, France"},{"name":"Micalis Institute, INRAE, AgroParisTech, Universit\u00e9 Paris-Saclay, 78350 Jouy-en-Josas, France"},{"name":"MGP, INRAE, Universit\u00e9 Paris-Saclay, 78350 Jouy-en-Josas, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6762-5350","authenticated-orcid":false,"given":"Magali","family":"Berland","sequence":"additional","affiliation":[{"name":"MGP, INRAE, Universit\u00e9 Paris-Saclay, 78350 Jouy-en-Josas, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3039-6718","authenticated-orcid":false,"given":"Olivier","family":"Langella","sequence":"additional","affiliation":[{"name":"PAPPSO, GQE-Le Moulon, AgroParisTech, CNRS, INRAE, Universit\u00e9 Paris-Saclay, 91190 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Sokol","sequence":"additional","affiliation":[{"name":"Micalis Institute, INRAE, AgroParisTech, Universit\u00e9 Paris-Saclay, 78350 Jouy-en-Josas, France"},{"name":"Gastroenterology Department, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Sorbonne Universit\u00e9, 75012 Paris, France"},{"name":"Paris Centre for Microbiome Medicine (PaCeMM) FHU, Service de Gastro-Ent\u00e9rologie et Nutrition, H\u00f4pital Saint-Antoine, Direction de la Recherche Clinique et de l\u2019Innovation (DRCI) de l\u2019AP-HP, CEDEX 12, 75571 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Juste","sequence":"additional","affiliation":[{"name":"Micalis Institute, INRAE, AgroParisTech, Universit\u00e9 Paris-Saclay, 78350 Jouy-en-Josas, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,14]]},"reference":[{"key":"ref_1","unstructured":"GBD 2017 Inflammatory Bowel Disease Collaborators (2020). The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990\u20132017: A systematic analysis for the global burden of diseases Study 2017. Lancet Gastroenterol. Hepatol., 5, 17\u201330."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/S2468-1253(19)30358-9","article-title":"Global burden of inflammatory bowel disease","volume":"5","author":"Jairath","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_3","first-page":"123","article-title":"The diagnosis and treatment of Crohn\u2019s disease and ulcerative colitis","volume":"106","author":"Baumgart","year":"2009","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15374","DOI":"10.3748\/wjg.v20.i41.15374","article-title":"Performance of the Montreal classification for inflammatory bowel diseases","volume":"20","author":"Spekhorst","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"493012","DOI":"10.1155\/2015\/493012","article-title":"Inflammatory Bowel Disease: An overview of immune mechanisms and biological treatments","volume":"2015","author":"Garcia","year":"2015","journal-title":"Mediators Inflamm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1172\/JCI118878","article-title":"Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27\/human beta2 microglobulin transgenic rats","volume":"98","author":"Rath","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/S0016-5085(98)70476-7","article-title":"Early lesions of recurrent Crohn\u2019s disease caused by infusion of intestinal contents in excluded ileum","volume":"114","author":"Geboes","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1016\/0016-5085(95)90121-3","article-title":"Controlled trial of metronidazole treatment for prevention of Crohn\u2019s recurrence after ileal resection","volume":"108","author":"Rutgeerts","year":"1995","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrg2203","article-title":"New links to the pathogenesis of Crohn disease provided by genome-wide association scans","volume":"9","author":"Mathew","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nri2340","article-title":"The genetics and immunopathogenesis of inflammatory bowel disease","volume":"8","author":"Cho","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1136\/gutjnl-2011-300777","article-title":"Genetic factors conferring an increased susceptibility to develop Crohn\u2019s disease also influence disease phenotype: Results from the IBDchip European Project","volume":"62","author":"Cleynen","year":"2013","journal-title":"Gut"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1056\/NEJMra0804647","article-title":"Inflammatory Bowel Disease","volume":"361","author":"Abraham","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/ajg.2018.27","article-title":"ACG Clinical Guideline: Management of Crohn\u2019s Disease in adults","volume":"113","author":"Lichtenstein","year":"2018","journal-title":"Am. J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"384","DOI":"10.14309\/ajg.0000000000000152","article-title":"ACG Clinical Guideline: Ulcerative Colitis in adults","volume":"114","author":"Rubin","year":"2019","journal-title":"Am. J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12","DOI":"10.4166\/kjg.2020.0119","article-title":"Therapeutic potential of Escherichia coli Nissle 1917 in clinically remission-attained Ulcerative Colitis patients: A hospital-based cohort study","volume":"77","author":"Oh","year":"2021","journal-title":"Korean J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.3748\/wjg.v27.i23.3317","article-title":"Can control of gut microbiota be a future therapeutic option for inflammatory bowel disease?","volume":"27","author":"Nishida","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1080\/10408398.2019.1599812","article-title":"Evolving trends in next-generation probiotics: A 5W1H perspective","volume":"60","author":"Almeida","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.clnu.2019.11.002","article-title":"ESPEN practical guideline: Clinical Nutrition in inflammatory bowel disease","volume":"39","author":"Bischoff","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"\u017b\u00f3\u0142kiewicz, J., Marzec, A., Ruszczy\u0144ski, M., and Feleszko, W. (2020). Postbiotics-A step beyond pre- and probiotics. Nutrients, 12.","DOI":"10.3390\/nu12082189"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s40168-020-0792-5","article-title":"Fecal microbiota transplantation to maintain remission in Crohn\u2019s disease: A pilot randomized controlled study","volume":"8","author":"Sokol","year":"2020","journal-title":"Microbiome"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mills, R.H., V\u00e1zquez-Baeza, Y., Zhu, Q., Jiang, L., Gaffney, J., Humphrey, G., Smarr, L., Knight, R., and Gonzalez, D.J. (2019). Evaluating metagenomic prediction of the metaproteome in a 4.5-year study of a patient with Crohn\u2019s disease. mSystems, 4.","DOI":"10.1128\/mSystems.00337-18"},{"key":"ref_22","first-page":"55","article-title":"OmpA variants affecting the adherence of ulcerative colitis-derived Bacteroides Vulgatus","volume":"57","author":"Sato","year":"2010","journal-title":"J. Med. Dent. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Erickson, A.R., Cantarel, B.L., Lamendella, R., Darzi, Y., Mongodin, E.F., Pan, C., Shah, M., Halfvarson, J., Tysk, C., and Henrissat, B. (2012). Integrated metagenomics\/metaproteomics reveals human host-microbiota signatures of Crohn\u2019s disease. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049138"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1136\/gutjnl-2012-303786","article-title":"Bacterial protein signals are associated with Crohn\u2019s disease","volume":"63","author":"Juste","year":"2014","journal-title":"Gut"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1038\/s41467-018-05357-4","article-title":"Metaproteomics reveals associations between microbiome and intestinal extracellular vesicle proteins in pediatric inflammatory bowel disease","volume":"9","author":"Zhang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jprot.2019.04.009","article-title":"Metaproteomics of fecal samples of Crohn\u2019s disease and ulcerative colitis","volume":"201","author":"Lehmann","year":"2019","journal-title":"J. Proteomics."},{"key":"ref_27","first-page":"1000197","article-title":"Quantitative metaproteomics and activity-based protein profiling of patient fecal microbiome identifies host and microbial serine-type endopeptidase activity associated with ulcerative colitis","volume":"21","author":"Wang","year":"2022","journal-title":"Mol. Cell. Proteomics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/978-1-4939-8814-3_8","article-title":"Metaproteomics study of the gut microbiome","volume":"1871","author":"Lai","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Issa Isaac, N., Philippe, D., Nicholas, A., Raoult, D., and Eric, C. (2019). Metaproteomics of the human gut microbiota: Challenges and contributions to other OMICS. Clin. Mass Spectrom., 18\u201330.","DOI":"10.1016\/j.clinms.2019.06.001"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lacroix, V., Cassard, A., Mas, E., and Barreau, F. (2021). Multi-Omics analysis of gut microbiota in inflammatory bowel diseases: What benefits for diagnostic, prognostic and therapeutic tools?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011255"},{"key":"ref_31","unstructured":"(2022, April 10). Metaproteomics Initiative. Available online: http:\/\/metaproteomics.org."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/s40168-021-01176-w","article-title":"The Metaproteomics Initiative: A coordinated approach for propelling the functional characterization of microbiomes","volume":"9","author":"Arntzen","year":"2021","journal-title":"Microbiome"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7305","DOI":"10.1038\/s41467-021-27542-8","article-title":"Critical Assessment of MetaProteome Investigation (CAMPI): A multi-laboratory comparison of established workflows","volume":"12","author":"Kunath","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1021\/acs.jproteome.0c00669","article-title":"Benefits of iterative searches of large databases to interpret large human gut metaproteomic data sets","volume":"20","author":"Bassignani","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1021\/acs.jproteome.6b00632","article-title":"X!TandemPipeline: A tool to manage sequence redundancy for protein inference and phosphosite identification","volume":"2","author":"Langella","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_36","unstructured":"(2022, April 10). PAPPSO, Plateforme d\u2019Analyse Prot\u00e9omique de Paris Sud-Ouest. Available online: http:\/\/pappso.inrae.fr\/."},{"key":"ref_37","unstructured":"(2022, April 11). Taxonomic and Functional Annotations of the Integrated Non-Redundant Gene Catalog 9.9. Available online: https:\/\/zenodo.org\/record\/3997093#.YlQepNPP1EY."},{"key":"ref_38","unstructured":"Bassignani, A. (2019). Metaproteomics analysis to study functionalities of the gut microbiota in large cohorts. [Ph.D. Thesis, Sorbonne University]. Thesis Defended."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1136\/gutjnl-2016-312135","article-title":"Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease","volume":"67","author":"Imhann","year":"2018","journal-title":"Gut"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17004","DOI":"10.1038\/nmicrobiol.2017.4","article-title":"Dynamics of the human gut microbiome in inflammatory bowel disease","volume":"2","author":"Halfvarson","year":"2017","journal-title":"Nat. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41564-018-0306-4","article-title":"Gut microbiome structure and metabolic activity in inflammatory bowel disease","volume":"4","author":"Franzosa","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_42","first-page":"597","article-title":"Fecal excretion of alpha 2-macroglobulin: A novel marker for disease activity in patients with inflammatory bowel disease","volume":"37","author":"Becker","year":"1999","journal-title":"Z. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/mi.2012.24","article-title":"The role of neutrophils during intestinal inflammation","volume":"5","author":"Fournier","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/156652413804486214","article-title":"Functions of S100 proteins","volume":"13","author":"Donato","year":"2013","journal-title":"Curr. Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.3389\/fimmu.2017.01908","article-title":"S100 proteins as an important regulator of macrophage inflammation","volume":"8","author":"Xia","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1136\/gut.52.6.847","article-title":"Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease","volume":"52","author":"Foell","year":"2003","journal-title":"Gut"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10555-020-09951-1","article-title":"Neutrophil-derived granule cargoes: Paving the way for tumor growth and progression","volume":"40","author":"Rawat","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_48","first-page":"e1004","article-title":"Fecal myeloperoxidase as a biomarker for inflammatory bowel disease","volume":"9","author":"Hansberry","year":"2017","journal-title":"Cureus"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s13059-019-1879-9","article-title":"Gut-derived Enterococcus faecium from ulcerative colitis patients promotes colitis in a genetically susceptible mouse host","volume":"20","author":"Seishima","year":"2019","journal-title":"Genome Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.chom.2014.02.005","article-title":"The treatment-naive microbiome in new-onset Crohn\u2019s disease","volume":"15","author":"Gevers","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_51","first-page":"143","article-title":"Antibodies to Coprococcus comes in sera of patients with Crohn\u2019s disease. Isolation and purification of the agglutinating antigen tested with an ELISA technique","volume":"23","author":"Hazenberg","year":"1987","journal-title":"J. Clin. Lab. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1053\/j.gastro.2008.04.025","article-title":"Raf protects against colitis by promoting mouse colon epithelial cell survival through NF-kappaB","volume":"135","author":"Edelblum","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/gigascience\/gix050","article-title":"Two distinct metacommunities characterize the gut microbiota in Crohn\u2019s disease patients","volume":"6","author":"He","year":"2017","journal-title":"GigaScience"},{"key":"ref_54","unstructured":"(2022, April 11). MassIVE, mass Spectrometry Interactive Virtual Environment. Available online: https:\/\/massive.ucsd.edu\/ProteoSAFe\/static\/massive.jsp."},{"key":"ref_55","unstructured":"(2022, April 10). INRAE, Institut National de Recherche pour L\u2019agriculture, L\u2019alimentation et L\u2019environnement. Available online: https:\/\/www.inrae.fr\/."},{"key":"ref_56","unstructured":"(2022, April 10). R\u00e9gion \u00eeledefrance, \u00c9ducation-Recherche. Available online: https:\/\/www.iledefrance.fr\/education-recherche."},{"key":"ref_57","unstructured":"(2022, April 10). IBiSA, Infrastructures en Biologie Sant\u00e9 et Agronomie. Available online: https:\/\/www.ibisa.net\/."},{"key":"ref_58","unstructured":"(2022, April 10). CNRS, Centre National de la Recherche Scientifique. Available online: http:\/\/www.cnrs.fr."},{"key":"ref_59","unstructured":"(2022, April 10). ProteomeXchange Consortium. Available online: http:\/\/proteomecentral.proteomexchange.org."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"D442","DOI":"10.1093\/nar\/gky1106","article-title":"The PRIDE database and related tools and resources in 2019: Improving support for quantification data","volume":"47","author":"Csordas","year":"2019","journal-title":"Nucleic Acids Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/8\/1340\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:54:09Z","timestamp":1760136849000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/8\/1340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,14]]},"references-count":60,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["cells11081340"],"URL":"https:\/\/doi.org\/10.3390\/cells11081340","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,14]]}}}