{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:59:04Z","timestamp":1785463144032,"version":"3.56.0"},"reference-count":70,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["iMetaOmics"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Gut\u2010derived 5\u2010hydroxytryptamine (5\u2010HT), known as serotonin, plays a crucial role in regulating gastrointestinal functions. However, the impact of disruptions in gut\u2010derived 5\u2010HT synthesis on the early gut microbiome and intestinal microenvironment remains unclear. In this study, LP533401, an inhibitor targeting peripheral 5\u2010HT synthesis, was administered orally to neonatal rats starting at 4 days post\u2010birth. By day 11, inhibition of gut\u2010derived 5\u2010HT resulted in altered colonic morphology, characterized by increased crypt depth and reduced myenteric thickness. To investigate the mechanisms underlying these alterations, we employed a combination of metagenomics, mucosal transcriptome, and untargeted metabolomics on colonic samples. Metagenome profiling revealed an upregulation in the microbial two\u2010component system (ko02020) and tyrosine metabolism (ko00350), with minimal effects on taxa abundances. Transcriptome profiling analysis indicated the discriminant expression of genes enriched in pathogen infection\u2010responsive signaling (e.g.,\n                    <jats:italic>Salmonella<\/jats:italic>\n                    and\n                    <jats:italic>Yersinia<\/jats:italic>\n                    infection) and the Wnt signaling pathway that affected stem cell proliferation. Consistent with increased crypt depth, marker genes related to cell proliferation were excessively activated. Metabolomics analysis indicated lower ascorbate level and higher succinic acid level, correlating with 5\u2010HT concentrations and increased crypt depth. Additionally, altered metabolic pathways (e.g., nucleotide metabolism, signal transduction, metabolism of cofactors\u00a0and vitamins) suggested an impact on the colonic function. In summary, early inhibition of gut\u2010derived 5\u2010HT may unfavorably reshape the colonic microenvironment, affecting gut morphology, microbial function, stem cell proliferation, and mucosal metabolism.\n                  <\/jats:p>","DOI":"10.1002\/imo2.34","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T23:35:24Z","timestamp":1728948924000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Integrated omics revealed the altered colonic microenvironment after inhibition of peripheral serotonin synthesis by LP533401"],"prefix":"10.1002","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1990-359X","authenticated-orcid":false,"given":"Yidan","family":"Ling","sequence":"first","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology Nanjing Agricultural University Nanjing China"},{"name":"National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology Nanjing Agricultural University Nanjing China"},{"name":"Department of Animal Science University of Arkansas Fayetteville Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuibing","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology Nanjing Agricultural University Nanjing China"},{"name":"National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqin","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology Nanjing Agricultural University Nanjing China"},{"name":"National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlong","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Cumming School of Medicine University of Calgary Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology Nanjing Agricultural University Nanjing China"},{"name":"National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.07.027"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0079-6107(93)90009-9"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.105"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22157931"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40104-023-00903-7"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.11.057"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6684-10.2011"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2007.00962.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1145-09.2009"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1720017115"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.04.024"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-022-00645-7"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606722104"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.15482"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0278-0"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1998.275.5.G869"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1720017115"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2018.03.004"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/aem.00992-22"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.115.223990"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/aro2.39"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00553"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2098"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.05.035"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.05312.x"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0540-4"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.05.004"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2019.01.004"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42788-0"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.873555"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3353-05.2006"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2022.03.002"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00435.2001"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP271754"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1054590"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.07.032"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201887"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.07.013"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002616"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1159\/000171600"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i26.4119"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11010025"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00840-2022"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0000000000000478"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12082263"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1089\/jmf.2023.k.0292"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(87)90621-7"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1080\/17450390903217523"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00477-z"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlad051"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16121871"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00319.2017"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.05.022"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-2-r19"},{"key":"e_1_2_11_56_1","doi-asserted-by":"crossref","unstructured":"Horai Hisayuki MasanoriArita ShigehikoKanaya YoshitoNihei TasukuIkeda KazuhiroSuwa YuyaOjima et al.2010\"MassBank: a Public Repository for Sharing Mass Spectral Data for Life Sciences.\"Journal of Mass Spectrometry45: 703\u201314.https:\/\/doi.org\/10.1002\/jms.1777","DOI":"10.1002\/jms.1777"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl838"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1039\/d0ra05326k"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2016.12.029"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.5b00354"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2011.319"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2011.335"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.135"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/cem.695"},{"key":"e_1_2_11_65_1","first-page":"161","article-title":"Psych: Procedures for Psychological, Psychometric, and Personality Research","volume":"337","author":"Revelle William","year":"2015","journal-title":"The Comprehensive R Archive Network"},{"key":"e_1_2_11_66_1","article-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2023","journal-title":"Foundation for Statistical Computing, Vienna, Austra"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4"},{"key":"e_1_2_11_68_1","unstructured":"Windows. One\u2010way ANOVA followed by Dunnett's Multiple Comparisons Test was Performed Using GraphPad Prism version 8.0.0 for GraphPad Software. San Diego CA."},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.85"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150181505"}],"container-title":["iMetaOmics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/imo2.34","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/imo2.34","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/imo2.34","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:23:01Z","timestamp":1785460981000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/imo2.34"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,14]]},"references-count":70,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/imo2.34"],"URL":"https:\/\/doi.org\/10.1002\/imo2.34","archive":["Portico"],"relation":{},"ISSN":["2996-9506","2996-9514"],"issn-type":[{"value":"2996-9506","type":"print"},{"value":"2996-9514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,14]]},"assertion":[{"value":"2024-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e34"}}