Integrated analysis of microbe-host interactions in Crohn's disease reveals potential mechanisms of microbial proteins on host gene expression
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.isci.2022.103963 http://hdl.handle.net/11449/239900 |
Resumo: | Inflammatory responses of the intestinal epithelial barrier in patients with Crohn's disease (CD), a chronic inflammatory bowel disease (IBD), are associated with gut microbial alterations. At a community level, there is scarce mechanistic evidence on the effects of gut microbial alterations on host mucosal barrier responses. We used a computational microbe-host interaction prediction framework based on network diffusion and systems biology to integrate publicly available paired gut microbial and intestinal gene expression datasets. The ileal signaling network potentially modulated by the microbiota was enriched with immune-related pathways such as those associated with IL-4, IL-2, IL-13, NFkB, and toll-like receptors. We identified bacterial proteins eliciting post-translational modifications on host receptors, resulting in the de-repression of pro-inflammatory cytokines via critical hub proteins such as NFkB. The signaling networks were over-represented with CD associated genes and CD drug targets. Using datasets generated from our validation cohorts, we confirmed some of the results. |
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Integrated analysis of microbe-host interactions in Crohn's disease reveals potential mechanisms of microbial proteins on host gene expressionGastroenterologyMicrobiomeMolecular geneticsInflammatory responses of the intestinal epithelial barrier in patients with Crohn's disease (CD), a chronic inflammatory bowel disease (IBD), are associated with gut microbial alterations. At a community level, there is scarce mechanistic evidence on the effects of gut microbial alterations on host mucosal barrier responses. We used a computational microbe-host interaction prediction framework based on network diffusion and systems biology to integrate publicly available paired gut microbial and intestinal gene expression datasets. The ileal signaling network potentially modulated by the microbiota was enriched with immune-related pathways such as those associated with IL-4, IL-2, IL-13, NFkB, and toll-like receptors. We identified bacterial proteins eliciting post-translational modifications on host receptors, resulting in the de-repression of pro-inflammatory cytokines via critical hub proteins such as NFkB. The signaling networks were over-represented with CD associated genes and CD drug targets. Using datasets generated from our validation cohorts, we confirmed some of the results.AbbVieJanssen Research and DevelopmentTakeda Pharmaceuticals North AmericaAmgen FoundationBiogenFerringKaryopharm TherapeuticsLeona M. and Harry B. Helmsley Charitable TrustNestlé Health SciencePfizerH2020 European Research CouncilFonds Wetenschappelijk OnderzoekKU Leuven Department of Chronic Diseases Metabolism and Ageing Translational Research Center for Gastrointestinal Disorders (TARGID) IBD group, ON I Herestraat 49 - box 701Institute of Biosciences São Paulo University (UNESP), SPDepartment of Gastroenterology and Hepatology University Hospitals Leuven KU LeuvenInstitute of Biosciences São Paulo University (UNESP), SPH2020 European Research Council: CrUCCialH2020 European Research Council: ERC-2015-AdG, 694679Fonds Wetenschappelijk Onderzoek: S008419NIBD groupUniversidade Estadual Paulista (UNESP)KU LeuvenSudhakar, PadhmanandAndrighetti, Tahila [UNESP]Verstockt, SareCaenepeel, ClaraFerrante, MarcSabino, JoãoVerstockt, BramVermeire, Severine2023-03-01T19:52:25Z2023-03-01T19:52:25Z2022-05-20info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.isci.2022.103963iScience, v. 25, n. 5, 2022.2589-0042http://hdl.handle.net/11449/23990010.1016/j.isci.2022.1039632-s2.0-85128358190Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengiScienceinfo:eu-repo/semantics/openAccess2023-03-01T19:52:25Zoai:repositorio.unesp.br:11449/239900Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:08:35.921293Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Integrated analysis of microbe-host interactions in Crohn's disease reveals potential mechanisms of microbial proteins on host gene expression |
title |
Integrated analysis of microbe-host interactions in Crohn's disease reveals potential mechanisms of microbial proteins on host gene expression |
spellingShingle |
Integrated analysis of microbe-host interactions in Crohn's disease reveals potential mechanisms of microbial proteins on host gene expression Sudhakar, Padhmanand Gastroenterology Microbiome Molecular genetics |
title_short |
Integrated analysis of microbe-host interactions in Crohn's disease reveals potential mechanisms of microbial proteins on host gene expression |
title_full |
Integrated analysis of microbe-host interactions in Crohn's disease reveals potential mechanisms of microbial proteins on host gene expression |
title_fullStr |
Integrated analysis of microbe-host interactions in Crohn's disease reveals potential mechanisms of microbial proteins on host gene expression |
title_full_unstemmed |
Integrated analysis of microbe-host interactions in Crohn's disease reveals potential mechanisms of microbial proteins on host gene expression |
title_sort |
Integrated analysis of microbe-host interactions in Crohn's disease reveals potential mechanisms of microbial proteins on host gene expression |
author |
Sudhakar, Padhmanand |
author_facet |
Sudhakar, Padhmanand Andrighetti, Tahila [UNESP] Verstockt, Sare Caenepeel, Clara Ferrante, Marc Sabino, João Verstockt, Bram Vermeire, Severine |
author_role |
author |
author2 |
Andrighetti, Tahila [UNESP] Verstockt, Sare Caenepeel, Clara Ferrante, Marc Sabino, João Verstockt, Bram Vermeire, Severine |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
IBD group Universidade Estadual Paulista (UNESP) KU Leuven |
dc.contributor.author.fl_str_mv |
Sudhakar, Padhmanand Andrighetti, Tahila [UNESP] Verstockt, Sare Caenepeel, Clara Ferrante, Marc Sabino, João Verstockt, Bram Vermeire, Severine |
dc.subject.por.fl_str_mv |
Gastroenterology Microbiome Molecular genetics |
topic |
Gastroenterology Microbiome Molecular genetics |
description |
Inflammatory responses of the intestinal epithelial barrier in patients with Crohn's disease (CD), a chronic inflammatory bowel disease (IBD), are associated with gut microbial alterations. At a community level, there is scarce mechanistic evidence on the effects of gut microbial alterations on host mucosal barrier responses. We used a computational microbe-host interaction prediction framework based on network diffusion and systems biology to integrate publicly available paired gut microbial and intestinal gene expression datasets. The ileal signaling network potentially modulated by the microbiota was enriched with immune-related pathways such as those associated with IL-4, IL-2, IL-13, NFkB, and toll-like receptors. We identified bacterial proteins eliciting post-translational modifications on host receptors, resulting in the de-repression of pro-inflammatory cytokines via critical hub proteins such as NFkB. The signaling networks were over-represented with CD associated genes and CD drug targets. Using datasets generated from our validation cohorts, we confirmed some of the results. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-05-20 2023-03-01T19:52:25Z 2023-03-01T19:52:25Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.isci.2022.103963 iScience, v. 25, n. 5, 2022. 2589-0042 http://hdl.handle.net/11449/239900 10.1016/j.isci.2022.103963 2-s2.0-85128358190 |
url |
http://dx.doi.org/10.1016/j.isci.2022.103963 http://hdl.handle.net/11449/239900 |
identifier_str_mv |
iScience, v. 25, n. 5, 2022. 2589-0042 10.1016/j.isci.2022.103963 2-s2.0-85128358190 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
iScience |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129291137843200 |