{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T12:46:37Z","timestamp":1771505197616,"version":"3.50.1"},"posted":{"date-parts":[[2023,5,17]]},"group-title":"Gastroenterology","reference-count":28,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>\n                    Even in the absence of inflammation, persistent symptoms in Crohn\u2019s disease (CD) are prevalent and negatively impact quality of life. We aimed to determine whether quiescent CD patients with persistent symptoms (\n                    <jats:bold>qCD+symptoms<\/jats:bold>\n                    ) have changes in microbial structure and functional potential compared to those without symptoms (\n                    <jats:bold>qCD-symptoms<\/jats:bold>\n                    ).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We performed a prospective multi-center observational study nested within the SPARC IBD study. CD patients were included if they had evidence of quiescent disease as defined by fecal calprotectin level &lt; 150 mcg\/g. Persistent symptoms were defined by the CD-PRO2 questionnaire. Active CD (\n                    <jats:bold>aCD<\/jats:bold>\n                    ), diarrhea-predominant irritable bowel syndrome (\n                    <jats:bold>IBS-D<\/jats:bold>\n                    ), and healthy controls (\n                    <jats:bold>HC<\/jats:bold>\n                    ) were included as controls. Stool samples underwent whole genome shotgun metagenomic sequencing.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    A total of 424 patients were analyzed, including 39 qCD+symptoms, 274 qCD-symptoms, 21 aCD, 40 IBS-D, and 50 HC. Patients with qCD+symptoms had a less diverse microbiome, including significant reductions in Shannon diversity (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;.001) and significant differences in microbial community structure (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;.0001), compared with qCD-symptoms, IBS-D, and HC. Further, patients with qCD+symptoms showed significant enrichment of bacterial species that are normal inhabitants of the oral microbiome, including\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    (q=.003) as well as depletion of important butyrate and indole producers, such as\n                    <jats:italic>Eubacterium rectale<\/jats:italic>\n                    (q=.001),\n                    <jats:italic>Lachnospiraceae spp<\/jats:italic>\n                    . (q&lt;.0001), and\n                    <jats:italic>Faecalibacterium prausnitzii<\/jats:italic>\n                    (q&lt;.0001), compared with qCD-symptoms. Finally, qCD+symptoms showed significant reductions in bacterial\n                    <jats:italic>tnaA<\/jats:italic>\n                    genes, which mediate tryptophan metabolism, as well as significant\n                    <jats:italic>tnaA<\/jats:italic>\n                    allelic variation, compared with qCD-symptoms.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The microbiome in patients with qCD+symptoms show significant changes in diversity, community profile, and composition compared with qCD-symptoms. Future studies will focus on the functional significance of these changes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>What You Need to Know<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Persistent symptoms in quiescent Crohn\u2019s disease (CD) are prevalent and lead to worse outcomes. While changes in the microbial community have been implicated, the mechanisms by which altered microbiota may lead to qCD+symptoms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>Quiescent CD patients with persistent symptoms demonstrated significant differences in microbial diversity and composition compared to those without persistent symptoms. Specifically, quiescent CD patients with persistent symptoms were enriched in bacterial species that are normal inhabitants of the oral microbiome but depleted in important butyrate and indole producers compared to those without persistent symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Implications for Patient Care<\/jats:title>\n                    <jats:p>Alterations in the gut microbiome may be a potential mediator of persistent symptoms in quiescent CD. Future studies will determine whether targeting these microbial changes may improve symptoms in quiescent CD.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.1101\/2023.05.16.23290065","type":"posted-content","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T14:50:14Z","timestamp":1684335014000},"source":"Crossref","is-referenced-by-count":3,"title":["The Fecal Microbiome in Quiescent Crohn\u2019s Disease with Persistent Gastrointestinal Symptoms Show Enrichment of Oral Microbes But Depletion of Butyrate and Indole Producers"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0009-5815","authenticated-orcid":false,"given":"Jonathan","family":"Golob","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9213-7850","authenticated-orcid":false,"given":"Krishna","family":"Rao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7631-9665","authenticated-orcid":false,"given":"Jeffrey","family":"Berinstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4584-4026","authenticated-orcid":false,"given":"William","family":"Chey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1746-2370","authenticated-orcid":false,"given":"Chung","family":"Owyang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1980-4178","authenticated-orcid":false,"given":"Nobuhiko","family":"Kamada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1602-4341","authenticated-orcid":false,"given":"Peter","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3687-2364","authenticated-orcid":false,"given":"Vincent","family":"Young","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4823-5805","authenticated-orcid":false,"given":"Shrinivas","family":"Bishu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4861-7646","authenticated-orcid":false,"given":"Allen","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023051904101568000_2023.05.16.23290065v1.1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312912"},{"key":"2023051904101568000_2023.05.16.23290065v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.260"},{"key":"2023051904101568000_2023.05.16.23290065v1.3","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.cgh.2016.05.012","article-title":"Negative Effects on Psychological Health and Quality of Life of Genuine Irritable Bowel Syndrome\u2013type Symptoms in Patients With Inflammatory Bowel Disease","volume":"15","year":"2017","journal-title":"Clinical Gastroenterology and Hepatology"},{"key":"2023051904101568000_2023.05.16.23290065v1.4","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1093\/ibd\/izy040","article-title":"The Association Between Sustained Poor Quality of Life and Future Opioid Use in Inflammatory Bowel Disease","volume":"24","year":"2018","journal-title":"Inflamm Bowel Dis"},{"key":"2023051904101568000_2023.05.16.23290065v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.218"},{"key":"2023051904101568000_2023.05.16.23290065v1.6","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.cgh.2016.09.012","article-title":"Factors That Predict High Health Care Utilization and Costs for Patients With Inflammatory Bowel Diseases","volume":"15","year":"2017","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2023051904101568000_2023.05.16.23290065v1.7","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.05.056"},{"key":"2023051904101568000_2023.05.16.23290065v1.8","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-304066"},{"key":"2023051904101568000_2023.05.16.23290065v1.9","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1093\/ecco-jcc\/jjx152","article-title":"Irritable Bowel-like Symptoms in Ulcerative Colitis are as Common in Patients in Deep Remission as in Inflammation: Results From a Population-based Study [the IBSEN Study]","volume":"12","year":"2018","journal-title":"Journal of Crohn\u2019s and Colitis"},{"key":"2023051904101568000_2023.05.16.23290065v1.10","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.cgh.2020.03.044","article-title":"Persistent Diarrhea in Patients With Crohn\u2019s Disease After Mucosal Healing Is Associated With Lower Diversity of the Intestinal Microbiome and Increased Dysbiosis","volume":"19","year":"2021","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2023051904101568000_2023.05.16.23290065v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.09.022"},{"key":"2023051904101568000_2023.05.16.23290065v1.12","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.cgh.2020.03.013","article-title":"Alterations in Fecal Microbiomes and Serum Metabolomes of Fatigued Patients With Quiescent Inflammatory Bowel Diseases","volume":"19","year":"2021","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2023051904101568000_2023.05.16.23290065v1.13","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1038\/s41467-018-05470-4","article-title":"Microbial tryptophan catabolites in health and disease","volume":"9","year":"2018","journal-title":"Nature Communications"},{"key":"2023051904101568000_2023.05.16.23290065v1.14","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1093\/ibd\/izab071","article-title":"The Development and Initial Findings of A Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD)","volume":"28","year":"2022","journal-title":"Inflamm Bowel Dis"},{"key":"2023051904101568000_2023.05.16.23290065v1.15","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.12.031"},{"key":"2023051904101568000_2023.05.16.23290065v1.16","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13001"},{"key":"2023051904101568000_2023.05.16.23290065v1.17","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s13059-021-02355-6","article-title":"geneshot: gene-level metagenomics identifies genome islands associated with immunotherapy response","volume":"22","year":"2021","journal-title":"Genome Biol"},{"key":"2023051904101568000_2023.05.16.23290065v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17041-7"},{"key":"2023051904101568000_2023.05.16.23290065v1.19","doi-asserted-by":"crossref","unstructured":"Beghini F , McIver LJ , Blanco-M\u00edguez A , et al. Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3. eLife 10:e65088.","DOI":"10.7554\/eLife.65088"},{"key":"2023051904101568000_2023.05.16.23290065v1.20","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1097\/MEG.0000000000000692","article-title":"Fecal calprotectin for the prediction of small-bowel Crohn\u2019s disease by capsule endoscopy: a systematic review and meta-analysis","volume":"28","year":"2016","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"2023051904101568000_2023.05.16.23290065v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.05.003"},{"key":"2023051904101568000_2023.05.16.23290065v1.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2114152118"},{"key":"2023051904101568000_2023.05.16.23290065v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.02.005"},{"key":"2023051904101568000_2023.05.16.23290065v1.24","doi-asserted-by":"crossref","first-page":"e148543","DOI":"10.1172\/jci.insight.148543","article-title":"A potential pathogenic association between periodontal disease and Crohn\u2019s disease","volume":"6","year":"2021","journal-title":"JCI Insight"},{"key":"2023051904101568000_2023.05.16.23290065v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2008.06.010"},{"key":"2023051904101568000_2023.05.16.23290065v1.26","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0000000000000526"},{"key":"2023051904101568000_2023.05.16.23290065v1.27","doi-asserted-by":"crossref","first-page":"13098","DOI":"10.1096\/fj.201901304R","article-title":"Hydrogen sulfide signaling in mitochondria and disease","volume":"33","year":"2019","journal-title":"FASEB J"},{"key":"2023051904101568000_2023.05.16.23290065v1.28","doi-asserted-by":"crossref","unstructured":"Clooney AG , Eckenberger J , Laserna-Mendieta E , et al. Ranking microbiome variance in inflammatory bowel disease: a large longitudinal intercontinental study. Gut June 2020.","DOI":"10.1136\/gutjnl-2020-321106"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.05.16.23290065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:33:59Z","timestamp":1768505639000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2023.05.16.23290065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,17]]},"references-count":28,"URL":"https:\/\/doi.org\/10.1101\/2023.05.16.23290065","relation":{},"subject":[],"published":{"date-parts":[[2023,5,17]]},"subtype":"preprint"}}