{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:54:33Z","timestamp":1774659273917,"version":"3.50.1"},"reference-count":88,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Phoenix Children\u2019s Hospital Foundation Leadership Grant","award":["GR39923"],"award-info":[{"award-number":["GR39923"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Inflammatory bowel disease (IBD), which includes Crohn\u2019s Disease (CD) and Ulcerative Colitis (UC), is a chronic gastrointestinal (GI) disorder affecting 1 in 100 people in the United States. Pediatric IBD (PIBD) is estimated to impact 15 per 100,000 children in North America. Factors such as the gut microbiome (GM), genetic predisposition to the disease, and certain environmental factors are thought to be involved in pathogenesis. However, the pathophysiology of IBD is incompletely understood, and diagnostic biomarkers and effective treatments, particularly for PIBD, are limited. Recent work suggests that these factors may interact to influence disease development, and multiomic approaches have emerged as promising tools to elucidate the pathophysiology. We employed metagenomics, metabolomics- and metatranscriptomics-based approaches to examine the microbiome, its genetic potential, and its activity to identify factors associated with PIBD. Metagenomics-based analyses revealed pathways such as octane oxidation and glycolysis that were differentially expressed in UC patients. Additionally, metatranscriptomics-based analyses suggested enrichment of glycan degradation and two component systems in UC samples as well as protein processing in the endoplasmic reticulum, ribosome, and protein export in CD and UC samples. In addition, metabolomics-based approaches revealed patterns of differentially abundant metabolites between healthy and PIBD individuals. Interestingly, overall microbiome community composition (as measured by alpha and beta diversity indices) did not appear to be associated with PIBD. However, we observed a small number of differentially abundant taxa in UC versus healthy controls, including members of the Classes Gammaproteobacteria and Clostridia as well as members of the Family Rikenellaceae. Accordingly, when identifying potential biomarkers for PIBD, our results suggest that multiomics-based approaches afford enhanced potential to detect putative biomarkers for PIBD compared to microbiome community composition sequence data alone.<\/jats:p>","DOI":"10.3390\/biom15050746","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T07:44:57Z","timestamp":1747813497000},"page":"746","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multiomics-Based Profiling of the Fecal Microbiome Reveals Potential Disease-Specific Signatures in Pediatric IBD (PIBD)"],"prefix":"10.3390","volume":"15","author":[{"given":"Anita H.","family":"DeSantis","sequence":"first","affiliation":[{"name":"School of Mathematical and Natural Sciences, Arizona State University, 4701 W. Thunderbird Rd, Glendale, AZ 85306, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Buss","sequence":"additional","affiliation":[{"name":"Biosciences Core, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ 85281, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keaton M.","family":"Coker","sequence":"additional","affiliation":[{"name":"School of Mathematical and Natural Sciences, Arizona State University, 4701 W. Thunderbird Rd, Glendale, AZ 85306, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1912-871X","authenticated-orcid":false,"given":"Brad A.","family":"Pasternak","sequence":"additional","affiliation":[{"name":"Phoenix Children\u2019s Hospital, 1919 E. Thomas Rd, Phoenix, AZ 85016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhua","family":"Chi","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Health North Building, Arizona State University, 550 N. 3rd St, Suite 501, Phoenix, AZ 85004, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-8958","authenticated-orcid":false,"given":"Jeffrey S.","family":"Patterson","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Health North Building, Arizona State University, 550 N. 3rd St, Suite 501, Phoenix, AZ 85004, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiwei","family":"Gu","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Health North Building, Arizona State University, 550 N. 3rd St, Suite 501, Phoenix, AZ 85004, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4950-9161","authenticated-orcid":false,"given":"Peter W.","family":"Jurutka","sequence":"additional","affiliation":[{"name":"School of Mathematical and Natural Sciences, Arizona State University, 4701 W. Thunderbird Rd, Glendale, AZ 85306, USA"},{"name":"College of Medicine, University of Arizona, 475 N. 5th St, Phoenix, AZ 85004, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5079-2999","authenticated-orcid":false,"given":"Todd R.","family":"Sandrin","sequence":"additional","affiliation":[{"name":"School of Mathematical and Natural Sciences, Arizona State University, 4701 W. Thunderbird Rd, Glendale, AZ 85306, USA"},{"name":"Center for Health through Microbiomes, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ 85281, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.3748\/wjg.v24.i25.2741","article-title":"Current global trends in the incidence of pediatric-onset inflammatory bowel disease","volume":"24","author":"Schwarz","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2022058037","DOI":"10.1542\/peds.2022-058037","article-title":"Pediatric Inflammatory Bowel Disease","volume":"151","author":"Bouhuys","year":"2023","journal-title":"Pediatrics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.14740\/gr2007","article-title":"Incidence of Inflammatory Bowel Disease in Children","volume":"18","author":"Krogulska","year":"2025","journal-title":"Gastroenterol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tartamus, G.V., Serban, D.E., Fogas, C.R., and Tantau, M.V. (2025). Pediatric Inflammatory Bowel Disease in Romania: The First Epidemiological Study of the North-West Region (2000\u20132020). Children, 12.","DOI":"10.3390\/children12040403"},{"key":"ref_5","first-page":"577","article-title":"Pediatric Inflammatory Bowel Disease","volume":"64","author":"Conrad","year":"2017","journal-title":"Pediatr. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.dld.2020.10.033","article-title":"IBDs and the pediatric age: Their peculiarities and the involvement of the microbiota","volume":"53","author":"Cococcioni","year":"2021","journal-title":"Dig. Liver Dis."},{"key":"ref_7","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":"2016","journal-title":"Gut"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nrgastro.2015.150","article-title":"The global burden of IBD: From 2015 to 2025","volume":"12","author":"Kaplan","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e094280","DOI":"10.1136\/bmjopen-2024-094280","article-title":"Gut microbiome predictors of advanced therapy response in Crohn\u2019s disease: Protocol for the OPTIMIST prospective, longitudinal, observational pilot study in Canada","volume":"15","author":"Massaro","year":"2025","journal-title":"BMJ Open"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"50","DOI":"10.5223\/pghn.2019.22.1.50","article-title":"Clinical Aspects and Treatments for Pediatric Inflammatory Bowel Diseases","volume":"22","author":"Moon","year":"2019","journal-title":"Pediatr. Gastroenterol. Hepatol. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1053\/j.gastro.2008.08.030","article-title":"Searching for New Clues in Inflammatory Bowel Disease: Tell Tales From Pediatric IBD Natural History Studies","volume":"135","author":"Kugathasan","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hracs, L., Windsor, J.W., Gorospe, J., Cummings, M., Coward, S., Buie, M.J., Quan, J., Goddard, Q., Caplan, L., and Markovinovi\u0107, A. (2025). Global evolution of inflammatory bowel disease across epidemiologic stages. Nature, 1\u20139.","DOI":"10.1038\/s41586-025-08940-0"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Aldars-Garc\u00eda, L., Chaparro, M., and Gisbert, J.P. (2021). Systematic Review: The Gut Microbiome and Its Potential Clinical Application in Inflammatory Bowel Disease. Microorganisms, 9.","DOI":"10.3390\/microorganisms9050977"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Miggiano, G.A.D., Gasbarrini, A., and Mele, M.C. (2019). What Is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms, 7.","DOI":"10.3390\/microorganisms7010014"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1146\/annurev-immunol-032414-112151","article-title":"Mechanisms of Pediatric Inflammatory Bowel Disease","volume":"34","author":"Peloquin","year":"2016","journal-title":"Annu. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Fiocchi, C. (2023). Omics and Multi-Omics in IBD: No Integration, No Breakthroughs. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914912"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s10539-016-9542-2","article-title":"It\u2019s the song, not the singer: An exploration of holobiosis and evolutionary theory","volume":"32","author":"Doolittle","year":"2016","journal-title":"Biol. Philos."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1080\/1354750X.2024.2438734","article-title":"The role of urine metabolomics in the diagnosis and management of adult and pediatric Crohn\u2019s disease and ulcerative colitis","volume":"30","author":"Baskaran","year":"2024","journal-title":"Biomarkers"},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1172\/JCI75436","article-title":"Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature","volume":"124","author":"Haberman","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Imhann, F., Van der Velde, K.J., Barbieri, R., Alberts, R., Voskuil, M.D., Vila, A.V., Collij, V., Spekhorst, L.M., Van der Sloot, K.W.J., and Peters, V. (2019). The 1000IBD project: Multi-omics data of 1000 inflammatory bowel disease patients; data release 1. BMC Gastroenterol., 19.","DOI":"10.1186\/s12876-018-0917-5"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/s41586-019-1237-9","article-title":"Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases","volume":"569","author":"Arze","year":"2019","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.pcl.2021.07.011","article-title":"Precision Medicine in Pediatric Inflammatory Bowel Disease","volume":"68","author":"Spencer","year":"2021","journal-title":"Pediatr. Clin. North Am."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4516","DOI":"10.1073\/pnas.1000080107","article-title":"Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample","volume":"108","author":"Caporaso","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","unstructured":"Caporaso, J.G., Ackermann, G., Apprill, A., Bauer, M., Berg-Lyons, D., Betley, J., Fierer, N., Fraser, L., Fuhrman, J.A., and Gilbert, J.A. (2023, May 31). EMP 16S Illumina Amplicon Protocol V.1. Available online: https:\/\/www.protocols.io\/view\/emp-16s-illumina-amplicon-protocol-nuudeww."},{"key":"ref_27","unstructured":"Andrews, S. (2019, August 01). FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12355","DOI":"10.1021\/acs.analchem.5b03812","article-title":"Globally Optimized Targeted Mass Spectrometry: Reliable Metabolomics Analysis with Broad Coverage","volume":"87","author":"Gu","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3124","DOI":"10.1021\/acs.jproteome.1c00019","article-title":"Early Breast Cancer Detection Using Untargeted and Targeted Metabolomics","volume":"20","author":"Wei","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"117155","DOI":"10.1016\/j.trac.2023.117155","article-title":"Recent review on selected xenobiotics and their impacts on gut microbiome and metabolome","volume":"166","author":"Jin","year":"2023","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"47005","DOI":"10.1289\/EHP13435","article-title":"In Vivo Tissue Distribution of Polystyrene or Mixed Polymer Microspheres and Metabolomic Analysis after Oral Exposure in Mice","volume":"132","author":"Garcia","year":"2024","journal-title":"Environ. Health Perspect."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12931-023-02441-2","article-title":"Multi-omic assessment shows dysregulation of pulmonary and systemic immunity to e-cigarette exposure","volume":"24","author":"Scieszka","year":"2023","journal-title":"Respir. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/toxsci\/kfad056","article-title":"Maternal PBDE exposure disrupts gut microbiome and promotes hepatic proinflammatory signaling in humanized PXR-transgenic mouse offspring over time","volume":"194","author":"Kim","year":"2023","journal-title":"Toxicol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.1038\/s41467-024-48355-5","article-title":"Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction","volume":"15","author":"Mohr","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11306-024-02115-0","article-title":"Comparison of reversed-phase, hydrophilic interaction, and porous graphitic carbon chromatography columns for an untargeted toxicometabolomics study in pooled human liver microsomes, rat urine, and rat plasma","volume":"20","author":"Hemmer","year":"2024","journal-title":"Metabolomics"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Dedon, L.R., Yuan, H., Chi, J., Gu, H., Arias, A.J., Covault, J.M., and Zhou, Y. (2025). Baseline gut microbiome and metabolites are correlated with changes in alcohol consumption in participants in a randomized Zonisamide clinical trial. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-92313-0"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Chi, J., Patterson, J.S., Jin, Y., Kim, K.J., Lalime, N., Hawley, D., Lewis, F., Li, L., Wang, X., and Campen, M.J. (2025). Metabolic Reprogramming in Gut Microbiota Exposed to Polystyrene Microplastics. Biomedicines, 13.","DOI":"10.3390\/biomedicines13020446"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/mas.21445","article-title":"HILIC-MS for metabolomics: An attractive and complementary approach to RPLC-MS","volume":"35","author":"Tang","year":"2016","journal-title":"Mass Spectrom. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhuang, X., Liu, C., Zhan, S., Tian, Z., Li, N., Mao, R., Zeng, Z., and Chen, M. (2021). Gut Microbiota Profile in Pediatric Patients With Inflammatory Bowel Disease: A Systematic Review. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.626232"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1093\/ecco-jcc\/jjv147","article-title":"Altered Fecal Microbiota in Paediatric Inflammatory Bowel Disease","volume":"9","author":"Maukonen","year":"2015","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.jpeds.2010.02.046","article-title":"Microbiota in Pediatric Inflammatory Bowel Disease","volume":"157","author":"Schwiertz","year":"2010","journal-title":"J. Pediatr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1002\/ibd.22860","article-title":"Alterations in the gut microbiome of children with severe ulcerative colitis","volume":"18","author":"Michail","year":"2012","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Papa, E., Docktor, M., Smillie, C., Weber, S., Preheim, S.P., Gevers, D., Giannoukos, G., Ciulla, D., Tabbaa, D., and Ingram, J. (2012). Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039242"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.jcmgh.2016.06.004","article-title":"A Disease-Associated Microbial and Metabolomics State in Relatives of Pediatric Inflammatory Bowel Disease Patients","volume":"2","author":"Jacobs","year":"2016","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1080\/00365521.2019.1644368","article-title":"The microbiome reflects diagnosis and predicts disease severity in paediatric onset inflammatory bowel disease","volume":"54","author":"Malham","year":"2019","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1128\/JCM.02574-12","article-title":"Longitudinal Analyses of Gut Mucosal Microbiotas in Ulcerative Colitis in Relation to Patient Age and Disease Severity and Duration","volume":"51","author":"Fite","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/nbt.3935","article-title":"Shotgun metagenomics, from sampling to analysis","volume":"35","author":"Quince","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1016\/j.csbj.2024.04.060","article-title":"Visualizing metagenomic and metatranscriptomic data: A comprehensive review","volume":"23","author":"Aplakidou","year":"2024","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_50","first-page":"G327","article-title":"Gut microbiota differs between children with Inflammatory Bowel Disease and healthy siblings in taxonomic and functional composition: A metagenomic analysis","volume":"312","author":"Knoll","year":"2017","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Thomann, A.K., W\u00fcstenberg, T., Wirbel, J., Knoedler, L.-L., Thomann, P.A., Zeller, G., Ebert, M.P., Lis, S., and Reindl, W. (2022). Depression and fatigue in active IBD from a microbiome perspective\u2014A Bayesian approach to faecal metagenomics. BMC Med., 20.","DOI":"10.1186\/s12916-022-02550-7"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zuo, W., Wang, B., Bai, X., Luan, Y., Fan, Y., Michail, S., and Sun, F. (2022). 16S rRNA and metagenomic shotgun sequencing data revealed consistent patterns of gut microbiome signature in pediatric ulcerative colitis. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-07995-7"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1146\/annurev-biodatasci-031121-103035","article-title":"Metatranscriptomics for the Human Microbiome and Microbial Community Functional Profiling","volume":"4","author":"Zhang","year":"2021","journal-title":"Annu. Rev. Biomed. Data Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s41564-017-0089-z","article-title":"Dynamics of metatranscription in the inflammatory bowel disease gut microbiome","volume":"3","author":"Schirmer","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.advms.2019.12.009","article-title":"Metabolomic profiling in children with inflammatory bowel disease","volume":"65","author":"Filimoniuk","year":"2020","journal-title":"Adv. Med. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1093\/ecco-jcc\/jjac079","article-title":"Faecal Metabolomics in Paediatric Inflammatory Bowel Disease: A Systematic Review","volume":"16","author":"Jagt","year":"2022","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Martin, F.-P., Ezri, J., Cominetti, O., Da Silva, L., Kussmann, M., Godin, J.-P., and Nydegger, A. (2016). Urinary Metabolic Phenotyping Reveals Differences in the Metabolic Status of Healthy and Inflammatory Bowel Disease (IBD) Children in Relation to Growth and Disease Activity. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17081310"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3643","DOI":"10.3748\/wjg.v23.i20.3643","article-title":"Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children","volume":"23","author":"Martin","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/apt.12861","article-title":"Metabolomic analysis of breath volatile organic compounds reveals unique breathprints in children with inflammatory bowel disease: A pilot study","volume":"40","author":"Patel","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Monasta, L., Pierobon, C., Princivalle, A., Martelossi, S., Marcuzzi, A., Pasini, F., and Perbellini, L. (2017). Inflammatory bowel disease and patterns of volatile organic compounds in the exhaled breath of children: A case-control study using Ion Molecule Reaction-Mass Spectrometry. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184118"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1093\/ibd\/izy402","article-title":"Untargeted Metabolomics and Inflammatory Markers Profiling in Children With Crohn\u2019s Disease and Ulcerative Colitis\u2014A Preliminary Study","volume":"25","author":"Daniluk","year":"2019","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_62","first-page":"321","article-title":"Faecal and serum metabolomics in paediatric inflammatory bowel disease","volume":"11","author":"Kolho","year":"2017","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Zhang, F., Guo, L., Shi, J., Jiang, H., Zhou, F., Zhou, Y., Lv, B., and Xu, M. (2023). Choline metabolism in regulating inflammatory bowel disease-linked anxiety disorders: A multi-omics exploration of the gut-brain axis. Neurobiol. Dis., 191.","DOI":"10.1016\/j.nbd.2023.106390"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1017\/S0007114520002639","article-title":"Insufficient dietary choline aggravates disease severity in a mouse model of Citrobacter rodentium-induced colitis","volume":"125","author":"Ju","year":"2020","journal-title":"Br. J. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Guo, L., Chen, Q., Gao, Y., Jiang, H., Zhou, F., Zhang, F., and Xu, M. (2023). CDP-choline modulates cholinergic signaling and gut microbiota to alleviate DSS-induced inflammatory bowel disease. Biochem. Pharmacol., 217.","DOI":"10.1016\/j.bcp.2023.115845"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s11306-014-0677-3","article-title":"Metabonomics of human fecal extracts characterize ulcerative colitis, Crohn\u2019s disease and healthy individuals","volume":"11","author":"Bjerrum","year":"2014","journal-title":"Metabolomics"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Tsuji, A., Ikeda, Y., Yoshikawa, S., Taniguchi, K., Sawamura, H., Morikawa, S., Nakashima, M., Asai, T., and Matsuda, S. (2023). The Tryptophan and Kynurenine Pathway Involved in the Development of Immune-Related Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065742"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1080\/08830185.2021.1954638","article-title":"Tryptophan metabolites modulate inflammatory bowel disease and colorectal cancer by affecting immune system","volume":"41","author":"Ala","year":"2021","journal-title":"Int. Rev. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"96","DOI":"10.5056\/jnm17021","article-title":"Gene Expression Profiling and Assessment of Vitamin D and Serotonin Pathway Variations in Patients With Irritable Bowel Syndrome","volume":"24","author":"Dussik","year":"2018","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Grozi\u0107, A., Coker, K., Dussik, C.M., Sabir, M.S., Sabir, Z., Bradley, A., Zhang, L., Park, J., Yale, S., and Kaneko, I. (2022). Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0275683"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1136\/flgastro-2018-101055","article-title":"Managing vitamin D deficiency in inflammatory bowel disease","volume":"10","author":"Nielsen","year":"2019","journal-title":"Front. Gastroenterol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/BF02068079","article-title":"Role of cytokines and platelet-activating factor in inflammatory bowel disease: Implications for therapy","volume":"39","author":"Nassif","year":"1996","journal-title":"Dis. Colon Rectum"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/0016-5085(88)90346-0","article-title":"Role of platelet-activating factor in ulcerative colitis: Enhanced production during active disease and inhibition by sulfasalazine and prednisolone","volume":"95","author":"Eliakim","year":"1988","journal-title":"Gastroenterology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1620\/tjem.207.65","article-title":"Diagnostic Value of the Serum Platelet-Activating Factor Acetylhydrolase Activity in Inflammatory Bowel Disease","volume":"207","author":"Oshimoto","year":"2005","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Lu, Y., Xiong, Y., Zhang, S., Wang, B., Feng, Y., Pu, Z., Wei, K., Chen, J., Chen, D., and Zhang, P. (2024). D-mannose reduces oxidative stress, inhibits inflammation, and increases treg cell proportions in mice with ulcerative colitis. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1454713"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4804","DOI":"10.1038\/s41467-022-32505-8","article-title":"Mannose ameliorates experimental colitis by protecting intestinal barrier integrity","volume":"13","author":"Dong","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/s41586-022-04648-7","article-title":"Discovery of bioactive microbial gene products in inflammatory bowel disease","volume":"606","author":"Zhang","year":"2022","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2177488","DOI":"10.1080\/19490976.2023.2177488","article-title":"Multiomic spatial analysis reveals a distinct mucosa-associated virome","volume":"15","author":"Yan","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1111\/apt.16086","article-title":"Multiomic features associated with mucosal healing and inflammation in paediatric Crohn\u2019s disease","volume":"52","author":"Taylor","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2154092","DOI":"10.1080\/19490976.2022.2154092","article-title":"Stool multi-omics for the study of host\u2013microbe interactions in inflammatory bowel disease","volume":"14","author":"Sauceda","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Wang, S., Kaur, S., Kunath, B.J., May, P., Richardson, L., Rogers, A.B., Wilmes, P., Finn, R.D., and Vizca\u00edno, J.A. (2025). An Approach to Integrate Metagenomics, Metatranscriptomics and Metaproteomics Data in Public Data Resources. Proteomics, e202500002.","DOI":"10.1002\/pmic.202500002"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"151456","DOI":"10.1016\/j.semperi.2021.151456","article-title":"Multi \u2018omic data integration: A review of concepts, considerations, and approaches","volume":"45","author":"Hollister","year":"2021","journal-title":"Semin. Perinatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.3748\/wjg.v27.i17.1920","article-title":"Artificial intelligence applications in inflammatory bowel disease: Emerging technologies and future directions","volume":"27","author":"Gubatan","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Dovrolis, N., Moschoviti, A., Fessatou, S., Karamanolis, G., Kolios, G., and Gazouli, M. (2023). Identifying Microbiome Dynamics in Pediatric IBD: More than a Family Matter. Biomedicines, 11.","DOI":"10.3390\/biomedicines11071979"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2317932","DOI":"10.1080\/19490976.2024.2317932","article-title":"The intestinal microbiome of inflammatory bowel disease across the pediatric age range","volume":"16","author":"Conrad","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_87","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_88","doi-asserted-by":"crossref","first-page":"S84","DOI":"10.1053\/j.gastro.2025.01.197","article-title":"A Multiomics-based Analysis of the Fecal Microbiome of Pediatric Inflammatory Bowel Disease (IBD) Patients Reveals Potential Disease-specific Features More Effectively Than Microbiome Community Composition Sequence Data","volume":"168","author":"Sandrin","year":"2025","journal-title":"Gastroenterology"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/5\/746\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:36:21Z","timestamp":1760031381000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/5\/746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,21]]},"references-count":88,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["biom15050746"],"URL":"https:\/\/doi.org\/10.3390\/biom15050746","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,21]]}}}