{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:17:30Z","timestamp":1778858250729,"version":"3.51.4"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC), a chronic inflammatory bowel disease. This study uniquely undertook a parallel, severity-stratified comparison of both fecal and mucosal microbiota and metabolites in UC patients. Our objective was to identify niche-specific (fecal vs. mucosal) and severity-associated microbial and metabolic signatures, clarifying its potential clinical utility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A prospective cohort study (ChiCTR2300071816) enrolled 83 UC patients (\u226518 years) from the First Affiliated Hospital of Nanjing Medical University and Northern Jiangsu People\u2019s Hospital (Jan 2022\u2013Dec 2024) and 30 healthy controls. Clinical data, stool, and rectal mucosal samples were collected. Metagenomic sequencing and metabolomics were performed. Disease severity was stratified by modified Mayo score to analyze microbiota diversity, differential genera, metabolites, and enriched metabolic pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fecal microbiota \u03b1-diversity was significantly lower in UC vs. controls (Shannon index 4.15\u00a0vs. 5.44, P\u00a0=\u00a00.005); mucosal diversity showed no difference (P\u00a0=\u00a00.63). Beta diversity did not differ. Severe UC exhibited a non-significant decrease in \u03b1-diversity (fecal: 3.99\u00a0vs. 4.37, P\u00a0=\u00a00.14; mucosal: 3.40\u00a0vs. 3.72, P\u00a0=\u00a00.92), significantly higher fecal\/mucosal Klebsiella abundance, and lower Erysipelatoclostridium and Blautia abundance vs. mild-to-moderate UC. Metabolomics identified 363 fecal differential metabolites (e.g. allopurinol, histidine), enriching tyrosine, and alanine\/aspartate\/glutamate metabolism pathways. Mucosal analysis revealed 127 differential metabolites (e.g. quinic acid, sphingosine), implicating sphingolipid metabolism and lysine synthesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>UC demonstrates gut dysbiosis and metabolic disruption correlating with severity. Elevated Klebsiella abundance suggests a pathogenic role in progression. Distinct fecal and mucosal metabolic pathway alterations provide novel insights for disease classification and therapeutic targeting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jambio\/lxag079","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T12:42:43Z","timestamp":1774010563000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Klebsiella<\/i>\n                    enrichment is associated with disease severity in ulcerative colitis"],"prefix":"10.1093","volume":"137","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University Department of Gastroenterology, , Yangzhou 225000, Jiangsu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Wu","sequence":"additional","affiliation":[{"name":"Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University Department of Endoscopy Center, , Yangzhou 225000, Jiangsu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University Department of Pharmacy, , Yangzhou 225000, Jiangsu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianqi","family":"Ren","sequence":"additional","affiliation":[{"name":"Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University Department of Gastroenterology, , Yangzhou 225000, Jiangsu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4497-0503","authenticated-orcid":false,"given":"Hongjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Nanjing Medical University Department of Gastroenterology, , Nanjing 210000, Jiangsu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University Department of Gastroenterology, , Yangzhou 225000, Jiangsu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"2026051510472901300_bib1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/nrgastro.2017.136","article-title":"Environmental triggers in IBD: a review of progress and evidence","volume":"15","author":"Ananthakrishnan","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2026051510472901300_bib2","doi-asserted-by":"publisher","first-page":"e0415222","DOI":"10.1128\/spectrum.04152-22","article-title":"Capsulized fecal microbiota transplantation induces remission in patients with ulcerative colitis by gut microbial colonization and metabolite regulation[J]","volume":"11","author":"Chen","year":"2023","journal-title":"Microbiol Spectr"},{"key":"2026051510472901300_bib3","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s40168-018-0449-9","article-title":"The active microbial community more accurately reflects the anaerobic digestion process: 16S rRNA (gene) sequencing as a predictive tool","volume":"6","author":"De\u00a0Vrieze","year":"2018","journal-title":"Microbiome"},{"key":"2026051510472901300_bib4","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1053\/j.gastro.2006.12.038","article-title":"A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis","volume":"132","author":"D\u2019Haens","year":"2007","journal-title":"Gastroenterology"},{"key":"2026051510472901300_bib5","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.3390\/ijms17071017","article-title":"Stable isotope-assisted evaluation of different extraction solvents for untargeted metabolomics of plants","volume":"17","author":"Doppler","year":"2016","journal-title":"Int J Mol Sci"},{"key":"2026051510472901300_bib6","doi-asserted-by":"publisher","first-page":"6966","DOI":"10.3390\/ijms23136966","article-title":"Inflammatory bowel disease treatments and predictive biomarkers of therapeutic response","volume":"23","author":"Elhag","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026051510472901300_bib7","doi-asserted-by":"publisher","first-page":"2879","DOI":"10.1016\/j.cell.2022.07.003","article-title":"Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation[J]","volume":"185","author":"Federici","year":"2022","journal-title":"Cell"},{"key":"2026051510472901300_bib8","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1053\/j.gastro.2020.01.006","article-title":"AGA Clinical Practice guidelines on the management of moderate to severe ulcerative colitis[J]","volume":"158","author":"Feuerstein","year":"2020","journal-title":"Gastroenterology"},{"key":"2026051510472901300_bib9","first-page":"796","article-title":"Consensus opinions on the diagnosis and treatment of inflammatory bowel disease (Beijing, 2018) [J]","volume":"38","author":"Kaichun","year":"2018","journal-title":"Chin J Pract Internal Med"},{"key":"2026051510472901300_bib10","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1186\/s12967-019-02174-1","article-title":"Integrating omics for a better understanding of Inflammatory Bowel disease: a step towards personalized medicine","volume":"17","author":"Kumar","year":"2019","journal-title":"J Transl Med"},{"key":"2026051510472901300_bib11","doi-asserted-by":"publisher","first-page":"17278","DOI":"10.1038\/s41598-018-35243-4","article-title":"IBD-Character Consortium. The prevalence and transcriptional activity of the mucosal microbiota of ulcerative colitis patients","volume":"8","author":"Moen","year":"2018","journal-title":"Sci Rep"},{"key":"2026051510472901300_bib12","doi-asserted-by":"publisher","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":"2026051510472901300_bib13","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1016\/S0140-6736(17)30182-4","article-title":"Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial","volume":"389","author":"Paramsothy","year":"2017","journal-title":"Lancet"},{"key":"2026051510472901300_bib14","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1053\/j.gastro.2019.11.294","article-title":"Differences in gut microbiota in patients with vs without inflammatory bowel diseases: a systematic review","volume":"158","author":"Pittayanon","year":"2020","journal-title":"Gastroenterology"},{"key":"2026051510472901300_bib15","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1099\/jmm.0.021170-0","article-title":"Transcriptional activity of the dominant gut mucosal microbiota in chronic inflammatory bowel disease patients","volume":"59","author":"Rehman","year":"2010","journal-title":"J Med Microbiol"},{"key":"2026051510472901300_bib16","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1136\/gutjnl-2014-308341","article-title":"Geographical patterns of the standing and active human gut microbiome in health and IBD","volume":"65","author":"Rehman","year":"2016","journal-title":"Gut"},{"key":"2026051510472901300_bib17","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1053\/j.gastro.2016.10.012","article-title":"Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches","volume":"152","author":"Sartor","year":"2017","journal-title":"Gastroenterology"},{"key":"2026051510472901300_bib18","doi-asserted-by":"publisher","first-page":"3188","DOI":"10.3390\/cells10113188","article-title":"Fecal microbiome changes and specific anti-bacterial response in patients with IBD during anti-TNF therapy","volume":"10","author":"Schierova","year":"2021","journal-title":"Cells"},{"key":"2026051510472901300_bib19","doi-asserted-by":"publisher","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":"2026051510472901300_bib20","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1136\/gutjnl-2016-313678","article-title":"Microbiomarkers in inflammatory bowel diseases: caveats come with caviar","volume":"66","author":"Sommer","year":"2017","journal-title":"Gut"},{"key":"2026051510472901300_bib21","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s00535-018-1488-5","article-title":"Differences in gut microbiota associated with age, sex, and stool consistency in healthy Japanese subjects","volume":"54","author":"Takagi","year":"2019","journal-title":"J Gastroenterol"},{"key":"2026051510472901300_bib22","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1053\/j.gastro.2013.07.024","article-title":"Reliability and initial validation of the ulcerative colitis endoscopic index of severity","volume":"145","author":"Travis","year":"2013","journal-title":"Gastroenterology"},{"key":"2026051510472901300_bib23","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1136\/gutjnl-2015-309618","article-title":"Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates","volume":"65","author":"Vandeputte","year":"2016","journal-title":"Gut"},{"key":"2026051510472901300_bib24","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1126\/science.1208344","article-title":"Linking long-term dietary patterns with gut microbial enterotypes","volume":"334","author":"Wu","year":"2011","journal-title":"Science"},{"key":"2026051510472901300_bib25","doi-asserted-by":"publisher","first-page":"6656","DOI":"10.1038\/s41467-022-34537-6","article-title":"Metabolite annotation from knowns to unknowns through knowledge-guided multi-layer metabolic networking","volume":"13","author":"Zhou","year":"2022","journal-title":"Nat Commun"}],"container-title":["Journal of Applied Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jambio\/advance-article-pdf\/doi\/10.1093\/jambio\/lxag079\/67434095\/lxag079.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jambio\/article-pdf\/137\/4\/lxag079\/67434095\/lxag079.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jambio\/article-pdf\/137\/4\/lxag079\/67434095\/lxag079.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:47:33Z","timestamp":1778856453000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jambio\/article\/doi\/10.1093\/jambio\/lxag079\/8530538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,20]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jambio\/lxag079","relation":{},"ISSN":["1365-2672"],"issn-type":[{"value":"1365-2672","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,3,20]]},"article-number":"lxag079"}}