Logo do repositório
 
Publicação

Alterations in mucosa branched N-glycans lead to dysbiosis and downregulation of ILC3: a key driver of intestinal inflammation

2025Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorRodrigues, Cláudia S.
dc.contributor.authorGaifem, Joana
dc.contributor.authorPereira, Márcia S.
dc.contributor.authorAlves, Maria Francisca
dc.contributor.authorSilva, Mariana
dc.contributor.authorPadrão, Nuno
dc.contributor.authorCavadas, Bruno
dc.contributor.authorMoreira-Barbosa, Catarina
dc.contributor.authorAlves, Inês
dc.contributor.authorMarcos-Pinto, Ricardo
dc.contributor.authorTorres, Joana
dc.contributor.authorLavelle, Aonghus
dc.contributor.authorColombel, Jean-Frederic
dc.contributor.authorSokol, Harry
dc.contributor.authorPinho, Salomé S.
dc.date.accessioned2025-02-11T14:22:06Z
dc.date.available2025-02-11T14:22:06Z
dc.date.issued2025
dc.description© 2025 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consentpt_PT
dc.description.abstractThe perturbation of the symbiotic relationship between microbes and intestinal immune system contributes to gut inflammation and Inflammatory Bowel Disease (IBD) development. The host mucosa glycans (glycocalyx) creates a major biological interface between gut microorganisms and host immunity that remains ill-defined. Glycans are essential players in IBD immunopathogenesis, even years before disease onset. However, how changes in mucosa glycosylation shape microbiome and how this impact gut immune response and inflammation remains to be clarified. Here, we revealed that alterations in the expression of complex branched N-glycans at gut mucosa surface, modeled in glycoengineered mice, resulted in dysbiosis, with a deficiency in Firmicutes bacteria. Concomitantly, this mucosa N-glycan switch was associated with a downregulation of type 3 innate lymphoid cells (ILC3)-mediated immune response, leading to the transition of ILC3 toward an ILC1 proinflammatory phenotype and increased TNFα production. In addition, we demonstrated that the mucosa glycosylation remodeling through prophylactic supplementation with glycans at steady state was able to restore microbial-derived short-chain fatty acids and microbial sensing (by NOD2 expression) alongside the rescue of the expression of ILC3 module, suppressing intestinal inflammation and controlling disease onset. In a complementary approach, we further showed that IBD patients, often displaying dysbiosis, exhibited a tendency of decreased MGAT5 expression at epithelial cells that was accompanied by reduced ILC3 expression in gut mucosa. Altogether, these results unlock the effects of alterations in mucosa glycome composition in the regulation of the bidirectional crosstalk between microbiota and gut immune response, revealing host branched N-glycans/microbiota/ILC3 axis as an essential pathway in gut homeostasis and in preventing health to intestinal inflammation transition.pt_PT
dc.description.sponsorshipCo-funded by the European Union under the Grant Agreement no. [101093997]. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or European Health and Digital Executive Agency (HADEA). Neither the European Union nor the granting authority can be held responsible for them. Salomé S. Pinho and Harry Sokol acknowledge funding from European Crohn’s and Colitis Organisation (ECCO) Pioneer Award 2021; Salomé S. Pinho also acknowledges the International Organization for the study of Inflammatory Bowel Disease (IOIBD).Cláudia Rodrigues thanks the Portuguese Foundation for Science and Technology (FCT) for funding (2020.08422.BD). Joana Gaifem acknowledges funding from European Society of Clinical Microbiology and Infectious Diseases (ESCMID Research Grant, 2022), European Crohn’s and Colitis Organisation (ECCO Grant, 2023) and FCT (DOI 10.54499/2020.00088.CEECIND/CP1608/CT0001). Márcia S. Pereira, Mariana Silva, Bruno Cavadas and Inês Alves acknowledge funding from FCT (SFRH/BD/110148/2015, SFRH/BD/136388/2018, CEECINST/00123/2021/CP1772/CT0001 and 2022.00337.CEECIND, respectively).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGut Microbes. 2025 Dec;17(1):2461210pt_PT
dc.identifier.doi10.1080/19490976.2025.2461210pt_PT
dc.identifier.eissn1949-0984
dc.identifier.issn1949-0976
dc.identifier.urihttp://hdl.handle.net/10400.5/98323
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherTaylor & Francispt_PT
dc.relation101093997pt_PT
dc.relationGlycans as dual orchestrators of microbiome and immune response in Inflammatory Bowel Disease pathogenesis: impact in new therapeutic strategies
dc.relationGlycans as dual regulatory elements in the crosstalk between microbiome and gut immune response: impact in IBD treatment
dc.relationGlycans as novel immunomodulators in Colorectal cancer: an opportunity for innovative immunotherapeutic strategies.
dc.relationNot Available
dc.relationUnmasking glycans in autoimmunity: Identification of the mechanisms underlying self/nonself recognition in Systemic Lupus Erythematosus
dc.relation.publisherversionhttps://www.tandfonline.com/journals/kgmi20pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectILC3pt_PT
dc.subjectN-glycanspt_PT
dc.subjectIntestinal inflammationpt_PT
dc.subjectMicrobiomept_PT
dc.subjectProphylaxispt_PT
dc.titleAlterations in mucosa branched N-glycans lead to dysbiosis and downregulation of ILC3: a key driver of intestinal inflammationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumber2020.08422.BD
oaire.awardNumber2020.00088.CEECIND/CP1608/CT0001
oaire.awardNumberSFRH/BD/110148/2015
oaire.awardNumberSFRH/BD/136388/2018
oaire.awardNumberCEECINST/00123/2021/CP1772/CT0001
oaire.awardNumber2022.00337.CEECIND/CP1735/CT0014
oaire.awardTitleGlycans as dual orchestrators of microbiome and immune response in Inflammatory Bowel Disease pathogenesis: impact in new therapeutic strategies
oaire.awardTitleGlycans as dual regulatory elements in the crosstalk between microbiome and gut immune response: impact in IBD treatment
oaire.awardTitleGlycans as novel immunomodulators in Colorectal cancer: an opportunity for innovative immunotherapeutic strategies.
oaire.awardTitleNot Available
oaire.awardTitleUnmasking glycans in autoimmunity: Identification of the mechanisms underlying self/nonself recognition in Systemic Lupus Erythematosus
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//2020.08422.BD/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND 3ed/2020.00088.CEECIND%2FCP1608%2FCT0001/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_NORTE/SFRH%2FBD%2F110148%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_NORTE/SFRH%2FBD%2F136388%2F2018/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC INST 2ed/CEECINST%2F00123%2F2021%2FCP1772%2FCT0001/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND5ed/2022.00337.CEECIND%2FCP1735%2FCT0014/PT
oaire.citation.issue1pt_PT
oaire.citation.titleGut Microbespt_PT
oaire.citation.volume17pt_PT
oaire.fundingStreamCEEC IND 3ed
oaire.fundingStreamPOR_NORTE
oaire.fundingStreamPOR_NORTE
oaire.fundingStreamCEEC INST 2ed
oaire.fundingStreamCEEC IND5ed
person.familyNameTorres
person.givenNameJoana
person.identifier.orcid0000-0003-2895-5821
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication38a18ac5-f4d2-4748-adf8-d41eefac84ab
relation.isAuthorOfPublication.latestForDiscovery38a18ac5-f4d2-4748-adf8-d41eefac84ab
relation.isProjectOfPublicationc45c4323-6d96-4d9f-bf6f-3e70fb8ec6c3
relation.isProjectOfPublicationeba0aaf7-62c3-49cd-90eb-beca0c42c99e
relation.isProjectOfPublicatione3d8e7d7-5346-4a58-90c9-5692a6d9f89b
relation.isProjectOfPublication54f7566d-344f-49ac-a4e1-5ae897810dcf
relation.isProjectOfPublication717ff493-edc0-4c03-8cc7-eb78d2e44386
relation.isProjectOfPublication1a6f4cbd-f4fa-4200-8f21-20cb36500bb4
relation.isProjectOfPublication.latestForDiscovery717ff493-edc0-4c03-8cc7-eb78d2e44386

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
Alterations_mucosa.pdf
Tamanho:
5.34 MB
Formato:
Adobe Portable Document Format
Ver/Abrir
Licença
A mostrar 1 - 1 de 1
Miniatura indisponível
Nome:
license.txt
Tamanho:
1.2 KB
Formato:
Item-specific license agreed upon to submission
Descrição:
Ver/Abrir

Coleções

FM - Artigos em Revistas Internacionais