A comprehensive time course and correlation analysis of indomethacin-induced inflammation, bile acid alterations and dysbiosis in the rat small intestine

https://m2.mtmt.hu/ eng 2026-10-24 21:10 JournalArticle 31998363 VALIDATED true Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [NKFI FK 124878]; Scientific and Innovative Research Fund of Semmelweis University [SE STIAKF17]; Higher Education Institutional Excellence Programme of the Ministry of Human Capacities; Research Excellence Programme of the National Research, Development and Innovation Office of the Ministry of Inno-vation and Technology in Hungary (TKP/ITM/NKFIH); Janos Bolyai Research Scholarships of the Hungarian Academy of Sciences; New National Excellence Program of the Ministry of Human Capacities [uNKP194]; [GINOP2.3.215201600048]; [EFOP3.6.216201700006] Funding text: The authors wish to express their thanks to Veronika PolMaruzs, Judit Simon, Patrik Palnok, Adam Lakos and David Szili for their tech-nical assistance. The graphical abstract contains artworks produced by Servier Medical Art (http://smart.servier.com ) . The research was supported by the National Research, Development and Innovation Office of Hungary (NKFI FK 124878) , GINOP2.3.215201600048 and EFOP3.6.216201700006, by the Scientific and Innovative Research Fund of Semmelweis University (SE STIAKF17) , and by the Higher Education Institutional Excellence Programme of the Ministry of Human Capacities, within the framework of the Neurology and the Therapy thematic programmes of the Semmelweis University (FIKP 2018) , and by the Research Excellence Programme of the National Research, Development and Innovation Office of the Ministry of Inno-vation and Technology in Hungary (TKP/ITM/NKFIH) . A. Kemeny was supported by Janos Bolyai Research Scholarships of the Hungarian Academy of Sciences, and by the New National Excellence Program of the Ministry of Human Capacities (uNKP194) . 0 false 2026-10-21T07:45:02.271+0000 2023-06-21T07:13:18.480+0000 2021-05-04T13:03:30.568+0000 true 10039043 Milánkovics Róbert /api/admin/10039043 Admin Róbert Milánkovics (PTE ÁOK admin 4) true 10039043 2026-07-28T07:58:36.089+0000 2023-06-21T07:13:18.964+0000 true 10039043 Milánkovics Róbert /api/admin/10039043 Admin Róbert Milánkovics (PTE ÁOK admin 4) true 10039043 Admin 10067876 /api/admin/10067876 Gusztáv Ladányi (MTMT API user, admin) Ladányi Gusztáv true true Admin 10097590 /api/admin/10097590 Zsófia Orbán (MTMT ellenőrzés, admin) Orbán Zsófia true true 2024-10-17T16:10:53.532+0000 true false true 24 24 /api/publicationtype/24 PublicationType Journal Article 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType Journal Article 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType Article (Journal Article) 101 true 10000059 true 1 /api/category/1 Category Scientific true 1 Lázár, Bernadette A comprehensive time course and correlation analysis of indomethacin-induced inflammation, bile acid alterations and dysbiosis in the rat small intestine true true /api/journal/686 REVIEWED BIOCHEMICAL PHARMACOLOGY 0006-2952 1873-2968 true false 686 false 686 true 0006-2952 1873-2968 Journal FOREIGN 190 114590 114590 15 2021 It has been proposed that changes in microbiota due to nonsteroidal anti-inflammatory drugs (NSAIDs) alter the composition of bile, and elevation of hydrophobic secondary bile acids contributes to small intestinal damage. However, little is known about the effect of NSAIDs on small intestinal bile acids, and whether bile alterations correlate with mucosal injury and dysbiosis. Here we determined the ileal bile acid metabolome and microbiota 24, 48 and 72 h after indomethacin treatment, and their correlation with each other and with tissue damage in rats. In parallel with the development of inflammation, indomethacin increased the ileal proportion of glycine and taurine conjugated bile acids, but not bile hydrophobicity. Firmicutes decreased with time, whereas Gammaproteobacteria increased first, but declined later and were partially replaced by Bilophila, Bacteroides and Fusobacterium. Mucosal injury correlated negatively with unconjugated bile acids and Gram-positive bacteria, and positively with taurine conjugates and some Gram-negative taxa. Strong positive correlation was found between Lactobacillaceae, Ruminococcaceae, Clostridiaceae and unconjugated bile acids. Indomethacin-induced dysbiosis was not likely due to direct antibacterial effects or alterations in luminal pH. Here we provide the first detailed characterization of indomethacin-induced time-dependent alterations in small intestinal bile acid composition, and their associations with mucosal injury and dysbiosis. Our results suggest that increased bile hydrophobicity is not likely to contribute to indomethacin-induced small intestinal damage. Funding 2001371 /api/funding/2001371 Modern orvostudományi diagnosztikus eljárások és terápiák fejlesztése transzlációs megközelítésbe...(EFOP-3.6.2-16-2017-00006) Funder: EFOP false true Funding 2001372 /api/funding/2001372 (GINOP-2.3.2-15-2016-00048) false true Funding 2007208 /api/funding/2007208 (ÚNKP-19-4) false true Funding 2007209 /api/funding/2007209 (NKFI FK 124878) false true Funding 2007210 /api/funding/2007210 (STIA-KF-17) Funder: STIA false true Funding 2007211 /api/funding/2007211 Programme of the Ministry of Human Capacities in Hungary(FIKP 2018) false true Funding 2007212 /api/funding/2007212 (TKP/ITM/NKFIH) false true Funding 2007213 /api/funding/2007213 (Janos Bolyai Research Fellowship) Funder: MTA Bolyai pályázat false true true 2021 true true true false true false GOLD 2026-10-21 true https://doi.org/10.1016/j.bcp.2021.114590 41 0 40 34 7 39 39 39 40 40 40 34 34 35 6 0 41 35 40 34 0 6 6 Folyóiratcikk Journal Article 24 40 Könyvrészlet Chapter in Book 25 0 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 1 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2021 0 1 1 1 1 2022 0 8 8 8 8 2023 0 12 11 12 11 2024 0 6 5 6 5 2025 0 9 8 9 8 2026 0 5 2 5 2 Q1 false 10017488,105,10034554 false false false 2021-05-19T12:28:41.774+0000 Farmakológiai és Farmakoterápiai Intézet (PTE / ÁOK); Farmakológiai és Farmakoterápiás Intézet (SE / AOK / I); Információs Technológiai és Bionikai Kar (PPKE); Molekuláris farmakológia kutatócsoport (PTE / SZKK); Orvosi Biológiai Intézet és Központi Elektronmi... (PTE / ÁOK); Orvosi Mikrobiológiai Intézet (SE / AOK / I); Orálbiológiai Tanszék (SE / FOK); Ökológiai Tanszék (ÁTE / BI) 21 86 8 22 0 true 10097590 10067876 Language 10002 /api/language/10002 English Angol English true 2 true PersonAuthorship 96183167 /api/authorship/96183167 Lázár, Bernadette [Lázár, Bernadette (Farmakológia), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I) 1 0.045454547 true false false Author 10057402 /api/author/10057402 Bernadette Lázár (Farmakológia) Lázár Bernadette true 10057402 true Lázár Bernadette true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96183168 /api/authorship/96183168 László, Szilvia B [László, Szilvia Bianka (Farmakológia), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I) 2 0.045454547 false false false Author 10064619 /api/author/10064619 Szilvia Bianka László (Farmakológia) László Szilvia Bianka true 10064619 true László Szilvia B true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96183169 /api/authorship/96183169 Hutka, Barbara [Hutka, Barbara (Farmakológia), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I) 3 0.045454547 false false false Author 10069237 /api/author/10069237 Barbara Hutka (Farmakológia) Hutka Barbara true true Hutka Barbara true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96183170 /api/authorship/96183170 Tóth, András S [Tóth, András Sebestyén (orvostudományok), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I) 4 0.045 false false false Author 10076872 /api/author/10076872 András Sebestyén Tóth (orvostudományok) Tóth András Sebestyén true true Tóth András S true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96183171 /api/authorship/96183171 Mohammadzadeh, Amir [Mohammadzadeh, Amir (Farmakológia), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I) 5 0.045454547 false false false Author 10061055 /api/author/10061055 Amir Mohammadzadeh (Farmakológia) Mohammadzadeh Amir true 10061055 true Mohammadzadeh Amir true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96183172 /api/authorship/96183172 Berekméri, Eszter [Berekméri, Eszter, author] Department of Pharmacology and Pharmacotherapy (SU / FM / I); 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A comprehensive time course and correlation analysis of indomethacin-induced inflammation, bile acid alterations and dysbiosis in the rat small intestine. (2021) BIOCHEMICAL PHARMACOLOGY 0006-2952 1873-2968 190<div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <a href="/gui2/?type=authors&mode=browse&sel=10057402" target="_blank">Lázár Bernadette (Lázár Bernadette Farmakológia) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy ;    <a href="/gui2/?type=authors&mode=browse&sel=10064619" target="_blank">László Szilvia B (László Szilvia Bianka Farmakológia) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy ;    <a href="/gui2/?type=authors&mode=browse&sel=10069237" target="_blank">Hutka Barbara (Hutka Barbara Farmakológia) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy ;    <a href="/gui2/?type=authors&mode=browse&sel=10076872" target="_blank">Tóth András S (Tóth András Sebestyén orvostudományok) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy ;    <a href="/gui2/?type=authors&mode=browse&sel=10061055" target="_blank">Mohammadzadeh Amir (Mohammadzadeh Amir Farmakológia) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy ;    <a href="/gui2/?type=authors&mode=browse&sel=10052116" target="_blank">Berekméri Eszter (Berekméri Eszter ) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy; UVMB/BI/Department for Ecology ;    <a href="/gui2/?type=authors&mode=browse&sel=10057401" target="_blank">Ágg Bence (Ágg Bence Farmakológia) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy ;    <a href="/gui2/?type=authors&mode=browse&sel=10051360" target="_blank">Balogh Mihály (Balogh Mihály gyógyszerészeti tudományok) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy ;    Sajtos Viktor ;    <a href="/gui2/?type=authors&mode=browse&sel=10015480" target="_blank">Király Kornél (Király Kornél P Farmakológia) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy ;    <a href="/gui2/?type=authors&mode=browse&sel=10015484" target="_blank">Al-Khrasani Mahmoud (Al-Khrasani Mahmoud Farmakológia) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy ;    <a href="/gui2/?type=authors&mode=browse&sel=105" target="_blank">Földes Anna (Földes Anna Molekulár biológia, Élettan) </a> SU/FD/Department of Oral Biology ;    <a href="/gui2/?type=authors&mode=browse&sel=10006652" target="_blank">Varga Gábor (Varga Gábor Élettan, orálbiológia) </a> SU/FD/Department of Oral Biology ;    <a href="/gui2/?type=authors&mode=browse&sel=10034793" target="_blank">Makra Nóra (Makra Nóra genomika, biológia) </a> SU/FM/I/Department of Medical Microbiology ;    <a href="/gui2/?type=authors&mode=browse&sel=10025780" target="_blank">Ostorházi Eszter (Ostorházi Eszter mikrobiológus) </a> SU/FM/I/Department of Medical Microbiology ;    <a href="/gui2/?type=authors&mode=browse&sel=10003357" target="_blank">Szabó Dóra (Szabó Dóra Mikrobiológia) </a> SU/FM/I/Department of Medical Microbiology ;    <a href="/gui2/?type=authors&mode=browse&sel=10034554" target="_blank">Ligeti Balázs (Ligeti Balázs Bioinformatika) </a> PPCU/Információs Technológiai és Bionikai Kar ;    <a href="/gui2/?type=authors&mode=browse&sel=10018850" target="_blank">Kemény Ágnes (Kemény Ágnes Molekuláris biológia) </a> UP/UPMS/Department of Pharmacology and Pharmacotherapy; UP/SZRC/Molecular Pharmacology Research Group; UP/UPMS/Department of Medical Biology and Central Electron Microscope Laboratory ;    <a href="/gui2/?type=authors&mode=browse&sel=10001426" target="_blank">Helyes Zsuzsanna (Helyes Zsuzsanna Neurofarmakológia) </a> UP/UPMS/Department of Pharmacology and Pharmacotherapy; UP/SZRC/Molecular Pharmacology Research Group ;    <a href="/gui2/?type=authors&mode=browse&sel=10010125" target="_blank">Ferdinandy Péter (Ferdinandy Péter Farmakológia, molekuláris medicina) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy ;    <a href="/gui2/?type=authors&mode=browse&sel=10007320" target="_blank">Gyires Klára (Gyires Klára Farmakológia, gasztrointesztinális farmakológia) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy ;    <a href="/gui2/?type=authors&mode=browse&sel=10017488" target="_blank">Zádori Zoltán S ✉ (Zádori Zoltán Sándor Farmakológia, gasztrointesztinális farmakológia) </a> SU/FM/I/Department of Pharmacology and Pharmacotherapy </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;31998363" target="_blank">A comprehensive time course and correlation analysis of indomethacin-induced inflammation, bile acid alterations and dysbiosis in the rat small intestine</a></div> <div> BIOCHEMICAL PHARMACOLOGY (<a target="_blank" href="https://portal.issn.org/resource/ISSN/0006-2952">0006-2952</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1873-2968">1873-2968</a>): 190 Paper 114590. 15 p. (2021) </div> <div class="pub-footer"> Language: English | <a style="color:blue" title="10.1016/j.bcp.2021.114590" target="_blank" href="https://doi.org/10.1016/j.bcp.2021.114590"> DOI </a> <a style="color:blue" title="000678069600001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000678069600001"> WoS </a> <a style="color:black" title="130582" target="_blank" href="https://real.mtak.hu/130582"> REAL </a> <a style="color:blue" title="85107162544" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85107162544"> Scopus </a> <a style="color:blue" title="33940029" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=33940029&dopt=Abstract"> PubMed </a> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Journal subject: Scopus - Biochemistry   Rank: Q1</div> <div class="journal-subject">Journal subject: Scopus - Pharmacology   Rank: Q1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> Citing papers: 41 | Independent citation: 35 | Self citation: 6 | Unknown citation: 0 | Number of citations in WoS: 39 | Number of citations in Scopus: 40 | WoS/Scopus assigned: 40 | Number of citations with DOI: 39 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;31998363&sort=publishedYear,desc&sort=title"> Number of cited publications: 6 </a> </div> <div class="mtid">Publication: 31998363 | Validated Core Citing | Journal Article ( Article ) | Scientific | PubMed XML </div> <div class="funder"> EMBERI ERŐFORRÁS FEJLESZTÉSI OPERATÍV PROGRAM (EFOP)(EFOP-3.6.2-162017-00006) Funder: NRDIO, GINOP - STAY ALIVE(GINOP-2.3.2-15-2016-00048) Funder: Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal, (ÚNKP-19-4), (NKFI FK 124878), (STIA-KF-17) Funder: STIA, Programme of the Ministry of Human Capacities in Hungary(FIKP 2018), (TKP/ITM/NKFIH), (Janos Bolyai Research Fellowship) Funder: MTA Bolyai pályázat </div> <div class="lastModified">Last Modified: 2023.06.21. 09:13 Róbert Milánkovics (PTE ÁOK admin 4) </div> <div class="lockedBy">Centrally managed 2024.10.17. 18:10 Gusztáv Ladányi (MTMT API user, admin) Zsófia Orbán (MTMT ellenőrzés, admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;">Comments: Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [NKFI FK 124878]; Scientific and Innovative Research Fund of Semmelweis University [SE STIAKF17]; Higher Education Institutional Excellence Programme of the Ministry of Human Capacities; Research Excellence Programme of the National Research, Development and Innovation Office of the Ministry of Inno...</pre> </div></div>