{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:21:09Z","timestamp":1789608069847,"version":"build-2803163510"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":39,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100019392","name":"NUTRIM School of Nutrition and Translational Research in Metabolism","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Crohn\u2019s disease (CD) is a chronic, relapsing\u2013remitting gastrointestinal inflammatory condition with a multifactorial etiology. At present, drug therapy is the most important treatment option. However, a substantial number of CD patients experience side effects and\/or nonresponse to medical drugs. In part, this might be attributed to the interaction of the intestinal microbiome with xenobiotics, such as medical drugs. The aim of this study was to explore the effect of the common CD drugs budesonide, 6-mercaptopurine (6-MP), as well as tofacitinib on the CD patient\u2019s microbiome in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We performed 16S rRNA gene-based bacterial community profiling and metaproteomic analyses on anaerobic ex vivo incubations of CD patient-derived fecal microbiota (FM) that were exposed to CD drugs or control conditions. Both bacterial community profiling and metaproteomics revealed larger differences in 24-h FM incubations between the five donor-derived FM samples than between the various drug incubations. Incubation of the FM of one of the donors with 6-MP or tofacitinib resulted in a significant alteration in the metaproteome when compared to the control condition, whereas no effect could be observed upon incubation with budesonide. Considering only bacterial proteins detected in at least 80% of either the drug or control FM incubations, 33 proteins were consistently more abundant and 93 less abundant in all five donor-derived samples with 6-MP incubation, distinguishing 6-MP from control conditions.<\/jats:p>\n                    <jats:p>\n                      In contrast to metaproteomic analyses, bacterial community profiling only detected a significantly lower relative abundance of\n                      <jats:italic>Colidextribacter<\/jats:italic>\n                      in 15\u00a0\u00b5g\/ml tofacitinib FM incubations. No alterations were detected in overall bacterial richness, diversity, or community structure in response to incubation with any of the drugs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tofacitinib and especially 6-MP significantly affect microbial function, but barely microbial composition in vitro. These drug-induced functional changes may subsequently influence host physiology and potentially inflammation in CD. Our findings emphasize the relevance to include functional microbial studies when investigating drug\u2013microbiota interactions. Further research is needed to elucidate the impact of 6-MP-induced microbial alterations on intestinal physiology and inflammation in CD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12915-026-02569-9","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T01:15:55Z","timestamp":1773450955000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["6-mercaptopurine and tofacitinib alter microbial protein expression but not composition in fecal microbiota incubations from Crohn\u2019s disease patients"],"prefix":"10.1186","volume":"24","author":[{"given":"Heike E. F.","family":"Becker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronny","family":"Mohren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. Giang","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc J. J.","family":"Derijks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy M. A. E.","family":"Jonkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Penders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"2569_CR1","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1016\/S0140-6736(12)60026-9","volume":"380","author":"DC Baumgart","year":"2012","unstructured":"Baumgart DC, Sandborn WJ. Crohn\u2019s disease. Lancet. 2012;380:1590\u2013605.","journal-title":"Lancet"},{"issue":"3","key":"2569_CR2","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1093\/ecco-jcc\/jjaa173","volume":"15","author":"D Wintjens","year":"2021","unstructured":"Wintjens D, Bergey F, Saccenti E, et al. Disease activity patterns of Crohn\u2019s disease in the first ten years after diagnosis in the population-based IBD South Limburg cohort. J Crohns Colitis. 2021;15(3):391\u2013400. https:\/\/doi.org\/10.1093\/ecco-jcc\/jjaa173.","journal-title":"J Crohns Colitis"},{"issue":"1","key":"2569_CR3","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1093\/ecco-jcc\/jjz180","volume":"14","author":"J Torres","year":"2020","unstructured":"Torres J, Bonovas S, Doherty G, et al. ECCO guidelines on therapeutics in Crohn\u2019s disease: medical treatment. J Crohns Colitis. 2020;14(1):4\u201322. https:\/\/doi.org\/10.1093\/ecco-jcc\/jjz180.","journal-title":"J Crohns Colitis"},{"key":"2569_CR4","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1016\/S0140-6736(16)31711-1","volume":"389","author":"J Torres","year":"2017","unstructured":"Torres J, Mehandru S, Colombel J, Peyrin-biroulet L. Crohn\u2019s disease. Lancet. 2017;389:1741\u201355. https:\/\/doi.org\/10.1016\/S0140-6736(16)31711-1.","journal-title":"Lancet"},{"key":"2569_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep35216","volume":"6","author":"DI Tedjo","year":"2016","unstructured":"Tedjo DI, Smolinska A, Savelkoul PH, et al. The fecal microbiota as a biomarker for disease activity in Crohn\u2019s disease. Sci Rep. 2016;6:1\u201310. https:\/\/doi.org\/10.1038\/srep35216.","journal-title":"Sci Rep"},{"issue":"5","key":"2569_CR6","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1136\/gutjnl-2016-313235","volume":"66","author":"V Pascal","year":"2017","unstructured":"Pascal V, Pozuelo M, Borruel N, et al. A microbial signature for Crohn\u2019s disease. Gut. 2017;66(5):813\u201322. https:\/\/doi.org\/10.1136\/gutjnl-2016-313235.","journal-title":"Gut"},{"issue":"1","key":"2569_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00974-4","volume":"7","author":"K Hou","year":"2022","unstructured":"Hou K, Wu ZX, Chen XY, et al. Microbiota in health and diseases. Signal Transduct Target Ther. 2022;7(1): 135. https:\/\/doi.org\/10.1038\/s41392-022-00974-4.","journal-title":"Signal Transduct Target Ther"},{"key":"2569_CR8","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/978-3-030-91051-8_7","volume":"89","author":"J Penders","year":"2022","unstructured":"Penders J, van Best N. The development of the gut microbiota in childhood and its distortion by lifestyle changes. Prog Inflamm Res. 2022;89:197\u2013219. https:\/\/doi.org\/10.1007\/978-3-030-91051-8_7.","journal-title":"Prog Inflamm Res"},{"issue":"10","key":"2569_CR9","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1093\/ecco-jcc\/jjz049","volume":"13","author":"G Galazzo","year":"2019","unstructured":"Galazzo G, Tedjo DI, Wintjens DSJ. Faecal microbiota dynamics and their relation to disease course in Crohn\u2019s disease. J Crohns Colitis. 2019;13(10):1273\u201382. https:\/\/doi.org\/10.1093\/ecco-jcc\/jjz049.","journal-title":"J Crohns Colitis"},{"issue":"7","key":"2569_CR10","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/j.tim.2017.11.002","volume":"26","author":"A Heintz-Buschart","year":"2018","unstructured":"Heintz-Buschart A, Wilmes P. Human gut microbiome: function matters. Trends Microbiol. 2018;26(7):563\u201374. https:\/\/doi.org\/10.1016\/j.tim.2017.11.002.","journal-title":"Trends Microbiol"},{"issue":"7698","key":"2569_CR11","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/nature25979","volume":"555","author":"L Maier","year":"2018","unstructured":"Maier L, Pruteanu M, Kuhn M. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555(7698):623\u20138. https:\/\/doi.org\/10.1038\/nature25979.","journal-title":"Nature"},{"issue":"1","key":"2569_CR12","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1053\/j.gastro.2021.07.050","volume":"162","author":"HEF Becker","year":"2022","unstructured":"Becker HEF, Penders J, Jonkers DMAE. Microbial metabolism of inflammatory bowel disease drugs: current evidence and clinical implementations. Gastroenterology. 2022;162(1):4\u20138. https:\/\/doi.org\/10.1053\/j.gastro.2021.07.050.","journal-title":"Gastroenterology"},{"key":"2569_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2023.1107976","volume":"14","author":"HEF Becker","year":"2023","unstructured":"Becker HEF, Demers K, Derijks LJJ, Jonkers DMAE, Penders J. Current evidence and clinical relevance of drug-microbiota interactions in inflammatory bowel disease. Front Microbiol. 2023;14:1\u201317. https:\/\/doi.org\/10.3389\/fmicb.2023.1107976.","journal-title":"Front Microbiol"},{"issue":"1","key":"2569_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2017.00527","volume":"8","author":"F Liu","year":"2017","unstructured":"Liu F, Ma R, Riordan SM. Azathioprine, mercaptopurine, and 5-aminosalicylic acid affect the growth of IBD-associated Campylobacter species and other enteric microbes. Front Microbiol. 2017;8(1):1\u201312. https:\/\/doi.org\/10.3389\/fmicb.2017.00527.","journal-title":"Front Microbiol"},{"issue":"1","key":"2569_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40168-020-00806-z","volume":"8","author":"L Li","year":"2020","unstructured":"Li L, Ning Z, Zhang X. RapidAIM: a culture- and metaproteomics-based rapid assay of individual microbiome responses to drugs. Microbiome. 2020;8(1):1\u201316. https:\/\/doi.org\/10.1186\/s40168-020-00806-z.","journal-title":"Microbiome"},{"issue":"4","key":"2569_CR16","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1080\/00365521.2019.1599064","volume":"54","author":"L Rindom Krogsgaard","year":"2019","unstructured":"Rindom Krogsgaard L, Kristian Munck L, Bytzer P, Wildt S. An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide. Scand J Gastroenterol. 2019;54(4):446\u201352. https:\/\/doi.org\/10.1080\/00365521.2019.1599064.","journal-title":"Scand J Gastroenterol"},{"issue":"1","key":"2569_CR17","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1097\/TP.0000000000001492","volume":"101","author":"J Tourret","year":"2017","unstructured":"Tourret J, Willing BP, Dion S, MacPherson J, Denamur E, Finlay BB. Immunosuppressive treatment alters secretion of ileal antimicrobial peptides and gut microbiota, and favors subsequent colonization by uropathogenic Escherichia coli. Transplantation. 2017;101(1):74\u201382. https:\/\/doi.org\/10.1097\/TP.0000000000001492.","journal-title":"Transplantation"},{"issue":"4","key":"2569_CR18","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.chom.2018.09.009","volume":"24","author":"M Schirmer","year":"2018","unstructured":"Schirmer M, Denson L, Vlamakis H, et al. Compositional and temporal changes in the gut microbiome of pediatric ulcerative colitis patients are linked to disease course. Cell Host Microbe. 2018;24(4):600-610.e4. https:\/\/doi.org\/10.1016\/j.chom.2018.09.009.","journal-title":"Cell Host Microbe"},{"issue":"12","key":"2569_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.25380\/iastate.10250774","volume":"14","author":"T Atherly","year":"2019","unstructured":"Atherly T, Rossi G, White R, et al. Glucocorticoid and dietary effects on mucosal microbiota in canine inflammatory bowel disease. PLoS ONE. 2019;14(12):1\u201315. https:\/\/doi.org\/10.25380\/iastate.10250774.","journal-title":"PLoS ONE"},{"issue":"10","key":"2569_CR20","doi-asserted-by":"publisher","first-page":"2207","DOI":"10.1016\/j.cgh.2020.10.025","volume":"19","author":"M Fenster","year":"2021","unstructured":"Fenster M, Alayo QA, Khatiwada A, et al. Real-world effectiveness and safety of tofacitinib in Crohn\u2019s disease and IBD-U: a multicenter study from the TROPIC consortium. Clin Gastroenterol Hepatol. 2021;19(10):2207-2209.e3. https:\/\/doi.org\/10.1016\/j.cgh.2020.10.025.","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2569_CR21","unstructured":"European Medicines Agency. Xeljanz. Medicines. https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/xeljanz. Published 2025."},{"key":"2569_CR22","unstructured":"Aspen Bad Oldesloe GmbH. Puri-Nethol package leaflet. 2024:1\u20138."},{"key":"2569_CR23","unstructured":"Dr. Falk Pharma GmbH. Budenofalk package leaflet. 2019:1\u20137."},{"issue":"7","key":"2569_CR24","doi-asserted-by":"publisher","first-page":"e241","DOI":"10.1016\/j.crohns.2012.09.009","volume":"7","author":"T Nic Suibhne","year":"2013","unstructured":"Nic Suibhne T, Raftery TC, McMahon O, Walsh C, O\u2019Morain C, O\u2019Sullivan M. High prevalence of overweight and obesity in adults with Crohn\u2019s disease: associations with disease and lifestyle factors. J Crohns Colitis. 2013;7(7):e241\u20138. https:\/\/doi.org\/10.1016\/j.crohns.2012.09.009.","journal-title":"J Crohns Colitis"},{"key":"2569_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2021.598232","volume":"12","author":"HEF Becker","year":"2021","unstructured":"Becker HEF, Jamin C, Bervoets L, et al. Higher prevalence of Bacteroides fragilis in Crohn\u2019s disease exacerbations and strain-dependent increase of epithelial resistance. Front Microbiol. 2021;12:1\u201313. https:\/\/doi.org\/10.3389\/fmicb.2021.598232.","journal-title":"Front Microbiol"},{"issue":"11","key":"2569_CR26","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/nbt.3960","volume":"35","author":"PI Costea","year":"2017","unstructured":"Costea PI, Zeller G, Sunagawa S, et al. Towards standards for human fecal sample processing in metagenomic studies. Nat Biotechnol. 2017;35(11):1069. https:\/\/doi.org\/10.1038\/nbt.3960.","journal-title":"Nat Biotechnol"},{"issue":"Suppl 1","key":"2569_CR27","doi-asserted-by":"publisher","first-page":"4516","DOI":"10.1073\/pnas.1000080107","volume":"108","author":"JG Caporaso","year":"2011","unstructured":"Caporaso JG, Lauber CL, Walters WA, et al. Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4516\u201322. https:\/\/doi.org\/10.1073\/pnas.1000080107.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"2569_CR28","doi-asserted-by":"publisher","first-page":"2527","DOI":"10.1021\/acs.analchem.0c04572","volume":"93","author":"STP Mezger","year":"2021","unstructured":"Mezger STP, Mingels AMA, Bekers O, Heeren RMA, Cillero-Pastor B. Mass spectrometry spatial-omics on a single conductive slide. Anal Chem. 2021;93(4):2527\u201333. https:\/\/doi.org\/10.1021\/acs.analchem.0c04572.","journal-title":"Anal Chem"},{"issue":"7","key":"2569_CR29","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","volume":"13","author":"BJ Callahan","year":"2016","unstructured":"Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581\u20133. https:\/\/doi.org\/10.1038\/nmeth.3869.","journal-title":"Nat Methods"},{"key":"2569_CR30","doi-asserted-by":"publisher","unstructured":"McLaren MR. Silva SSU taxonomic training data formatted for DADA2 (Silva version 138). https:\/\/doi.org\/10.5281\/zenodo.3986799","DOI":"10.5281\/zenodo.3986799"},{"issue":"1","key":"2569_CR31","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-018-0605-2","volume":"6","author":"NM Davis","year":"2018","unstructured":"Davis NM, Proctor DM, Holmes SP, Relman DA, Callahan BJ. Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome. 2018;6(1): 226. https:\/\/doi.org\/10.1186\/s40168-018-0605-2.","journal-title":"Microbiome"},{"issue":"3","key":"2569_CR32","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/s41596-019-0264-1","volume":"15","author":"J Chong","year":"2020","unstructured":"Chong J, Liu P, Zhou G, Xia J. Using microbiomeanalyst for comprehensive statistical, functional, and meta-analysis of microbiome data. Nat Protoc. 2020;15(3):799\u2013821. https:\/\/doi.org\/10.1038\/s41596-019-0264-1.","journal-title":"Nat Protoc"},{"issue":"1","key":"2569_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13059-022-02655-5","volume":"23","author":"H Zhou","year":"2022","unstructured":"Zhou H, He K, Chen J, Zhang X. LinDA: linear models for differential abundance analysis of microbiome compositional data. Genome Biol. 2022;23(1):1\u201323. https:\/\/doi.org\/10.1186\/s13059-022-02655-5.","journal-title":"Genome Biol"},{"key":"2569_CR34","unstructured":"R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2014. Available from: https:\/\/www.R-project.org\/. (ISBN: 3-900051-07-0)."},{"issue":"8","key":"2569_CR35","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/nbt.2942","volume":"32","author":"J Li","year":"2014","unstructured":"Li J, Jia H, Cai X. An integrated catalog of reference genes in the human gut microbiome. Nat Biotechnol. 2014;32(8):834\u201345. https:\/\/doi.org\/10.1038\/nbt.2942.","journal-title":"Nat Biotechnol"},{"issue":"4","key":"2569_CR36","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.jmb.2015.11.006","volume":"428","author":"M Kanehisa","year":"2016","unstructured":"Kanehisa M, Sato Y, Morishima K. BlastKOALA and GhostKOALA: KEGG tools for functional characterization of genome and metagenome sequences. J Mol Biol. 2016;428(4):726\u201331. https:\/\/doi.org\/10.1016\/j.jmb.2015.11.006.","journal-title":"J Mol Biol"},{"issue":"2","key":"2569_CR37","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1021\/acs.jproteome.8b00716","volume":"18","author":"R Gurdeep Singh","year":"2019","unstructured":"Gurdeep Singh R, Tanca A, Palomba A, et al. Unipept 4.0: functional analysis of metaproteome data. J Proteome Res. 2019;18(2):606\u201315. https:\/\/doi.org\/10.1021\/acs.jproteome.8b00716.","journal-title":"J Proteome Res"},{"issue":"Database issue","key":"2569_CR38","doi-asserted-by":"publisher","first-page":"D136","DOI":"10.1093\/nar\/gkr1178","volume":"40","author":"S Federhen","year":"2012","unstructured":"Federhen S. The NCBI taxonomy database. Nucleic Acids Res. 2012;40(Database issue):D136\u201343. https:\/\/doi.org\/10.1093\/nar\/gkr1178.","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"2569_CR39","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1007\/s40262-018-0639-4","volume":"57","author":"LJJ Derijks","year":"2018","unstructured":"Derijks LJJ, Wong DR, Hommes DW, VanBodegraven AA. Clinical pharmacokinetic and pharmacodynamic considerations in the treatment of inflammatory bowel disease. Clin Pharmacokinet. 2018;57(9):1075\u2013106. https:\/\/doi.org\/10.1007\/s40262-018-0639-4.","journal-title":"Clin Pharmacokinet"},{"issue":"11","key":"2569_CR40","doi-asserted-by":"publisher","first-page":"4342","DOI":"10.1128\/IAI.05592-11","volume":"79","author":"D Raghunathan","year":"2011","unstructured":"Raghunathan D, Wells TJ, Morris FC. SadA, a trimeric autotransporter from Salmonella enterica serovar Typhimurium, can promote biofilm formation and provides limited protection against infection. Infect Immun. 2011;79(11):4342\u201352. https:\/\/doi.org\/10.1128\/IAI.05592-11.","journal-title":"Infect Immun"},{"issue":"6","key":"2569_CR41","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1093\/ecco-jcc\/jjaa252","volume":"15","author":"R Ventin-Holmberg","year":"2021","unstructured":"Ventin-Holmberg R, Eberl A, Saqib S. Bacterial and fungal profiles as markers of infliximab drug response in inflammatory bowel disease. J Crohns Colitis. 2021;15(6):1019\u201331. https:\/\/doi.org\/10.1093\/ecco-jcc\/jjaa252.","journal-title":"J Crohns Colitis"},{"issue":"3","key":"2569_CR42","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1136\/gutjnl-2020-321747","volume":"70","author":"M Fassarella","year":"2021","unstructured":"Fassarella M, Blaak EE, Penders J, Nauta A, Smidt H, Zoetendal EG. Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health. Gut. 2021;70(3):595\u2013605. https:\/\/doi.org\/10.1136\/gutjnl-2020-321747.","journal-title":"Gut"},{"key":"2569_CR43","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00403","volume":"10","author":"G Galazzo","year":"2020","unstructured":"Galazzo G, Best N, van BJ Benedikter v. How to count our microbes? The effect of different quantitative microbiome profiling approaches. Front Cell Infect Microbiol. 2020;10:403. https:\/\/doi.org\/10.3389\/fcimb.2020.00403.","journal-title":"Front Cell Infect Microbiol"},{"issue":"1","key":"2569_CR44","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","volume":"19","author":"YFO Pedersen","year":"2021","unstructured":"Pedersen YFO. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol. 2021;19(1):55\u201371. https:\/\/doi.org\/10.1038\/s41579-020-0433-9.","journal-title":"Nat Rev Microbiol"},{"issue":"3","key":"2569_CR45","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1128\/mmbr.00009-11","volume":"75","author":"N Verstraeten","year":"2011","unstructured":"Verstraeten N, Fauvart M, Vers\u00e9es W, Michiels J. The universally conserved prokaryotic GTPases. Microbiol Mol Biol Rev. 2011;75(3):507\u201342. https:\/\/doi.org\/10.1128\/mmbr.00009-11.","journal-title":"Microbiol Mol Biol Rev"},{"issue":"11","key":"2569_CR46","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1080\/1744666X.2018.1532291","volume":"14","author":"A Fern\u00e1ndez-Clotet","year":"2018","unstructured":"Fern\u00e1ndez-Clotet A, Castro-Poceiro J, Pan\u00e9s J. Tofacitinib for the treatment of ulcerative colitis. Expert Rev Clin Immunol. 2018;14(11):881\u201392. https:\/\/doi.org\/10.1080\/1744666X.2018.1532291.","journal-title":"Expert Rev Clin Immunol"},{"key":"2569_CR47","unstructured":"NCBI. Protein BLAST. https:\/\/blast.ncbi.nlm.nih.gov\/Blast.cgi. Accessed November 19, 2020."},{"key":"2569_CR48","unstructured":"EMBL-EBI. Protein Data Bank in Europe. https:\/\/www.ebi.ac.uk\/pdbe\/. Accessed November 19, 2020."},{"issue":"11","key":"2569_CR49","doi-asserted-by":"publisher","first-page":"3748","DOI":"10.1128\/JB.00169-06","volume":"188","author":"J Abranches","year":"2006","unstructured":"Abranches J, Candella MM, Wen ZT, Baker HV, Burne RA. Different roles of EIIAB man and EII Glc in regulation of energy metabolism, biofilm development, and competence in Streptococcus mutans. J Bacteriol. 2006;188(11):3748\u201356. https:\/\/doi.org\/10.1128\/JB.00169-06.","journal-title":"J Bacteriol"},{"issue":"21","key":"2569_CR50","doi-asserted-by":"publisher","first-page":"5086","DOI":"10.1016\/S0021-9258(18)99479-2","volume":"242","author":"V Sapico","year":"1967","unstructured":"Sapico V, Anderson RL. An adenosine 5\u2019-triphosphate:hexose 6-phosphotransferase specific for d-mannose and d-fructose from leuconostoc mesenteroides. J Biol Chem. 1967;242(21):5086\u201392. https:\/\/doi.org\/10.1016\/S0021-9258(18)99479-2.","journal-title":"J Biol Chem"},{"issue":"1","key":"2569_CR51","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1128\/iai.30.1.43-50.1980","volume":"30","author":"EV Porter","year":"1980","unstructured":"Porter EV, Chassy BM, Holmlund CE. Partial purification and properties of a mannofructokinase from Streptococcus mutans SL-1. Infect Immun. 1980;30(1):43\u201350. https:\/\/doi.org\/10.1128\/iai.30.1.43-50.1980.","journal-title":"Infect Immun"},{"issue":"6","key":"2569_CR52","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1128\/jb.177.6.1620-1623.1995","volume":"177","author":"SY Hou","year":"1995","unstructured":"Hou SY, Chao YP, Liao JC. A mutant phosphoenolpyruvate carboxykinase in Escherichia coli conferring oxaloacetate decarboxylase activity. J Bacteriol. 1995;177(6):1620\u20133. https:\/\/doi.org\/10.1128\/jb.177.6.1620-1623.1995.","journal-title":"J Bacteriol"},{"key":"2569_CR53","unstructured":"Madigan MT, Martinko JM, Dunlap PV, Clark DP. Metabolic diversity: catabolism of organic compounds. In: Brock Biology of Microorganisms. 12th ed. San Francisco (CA): Pearson\/Benjamin Cummings; 2009. p. 614."},{"key":"2569_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103293","volume":"66","author":"S Deleu","year":"2021","unstructured":"Deleu S, Machiels K, Raes J, Verbeke K, Vermeire S. Short chain fatty acids and its producing organisms: an overlooked therapy for IBD? EBioMedicine. 2021;66: 103293. https:\/\/doi.org\/10.1016\/j.ebiom.2021.103293.","journal-title":"EBioMedicine"},{"key":"2569_CR55","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-024-00526-4","volume":"10","author":"A Tanca","year":"2024","unstructured":"Tanca A, Palomba A, Fiorino G, Abbondio M, Pagnozzi D, Uzzau S. Metaproteomic portrait of the healthy human gut microbiota. NPJ Biofilms Microbiomes. 2024;10: 54.","journal-title":"NPJ Biofilms Microbiomes"},{"key":"2569_CR56","unstructured":"Becker HEF, Mohren R, Le GN, Derijks LJJ, Jonkers DMAE, Penders J. Crohn\u2019s disease patients 16S gut microbiota from in vitro xenobiotic experiments. European Nucleotide Archive. https:\/\/www.ebi.ac.uk\/ena\/browser\/view\/PRJEB79375. Published 2025."},{"issue":"D1","key":"2569_CR57","doi-asserted-by":"publisher","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","volume":"50","author":"Y Perez-Riverol","year":"2022","unstructured":"Perez-Riverol Y, Bai J, Bandla C. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 2022;50(D1):D543\u201352. https:\/\/doi.org\/10.1093\/nar\/gkab1038.","journal-title":"Nucleic Acids Res"},{"key":"2569_CR58","doi-asserted-by":"publisher","unstructured":"Mohren R. Human microbiome LC-MS proteomics in Crohn\u2019s disease patients. ProteomeXchange. https:\/\/doi.org\/10.6019\/PXD054714","DOI":"10.6019\/PXD054714"}],"container-title":["BMC Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12915-026-02569-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12915-026-02569-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12915-026-02569-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:11:39Z","timestamp":1776816699000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12915-026-02569-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,14]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2569"],"URL":"https:\/\/doi.org\/10.1186\/s12915-026-02569-9","relation":{},"ISSN":["1741-7007"],"issn-type":[{"value":"1741-7007","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,14]]},"assertion":[{"value":"16 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All participants gave written informed consent prior to participation. The IBD-SL cohort was approved by the Medical Ethics Committee of the Maastricht University Medical Centre\u2009+\u2009(IBD-SL: NL31636.068.10) and registered on\n                      \n                      (NCT02130349).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"101"}}