Growth differentiation factor 11 delivered by dairy Lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis

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dc.creatorMonique Ferrary Américo
dc.creatorAndria dos Santos Freitas
dc.creatorTales Fernando da Silva
dc.creatorLuís Cláudio Lima de Jesus
dc.creatorFernanda Alvarenga Lima Barroso
dc.creatorGabriela Munis Campos
dc.creatorRhayane Cristina Viegas Santos
dc.creatorGabriel Camargos Gomes
dc.creatorRafael Assis
dc.creatorÊnio Ferreira
dc.creatorPamela Mancha-Agresti
dc.creatorJuliana Guimarães Laguna
dc.creatorJean-Marc Chatel
dc.creatorRodrigo Dias de Oliveira Carvalho
dc.creatorVasco Azevedo
dc.date.accessioned2025-01-22T22:07:01Z
dc.date.accessioned2025-09-09T01:10:03Z
dc.date.available2025-01-22T22:07:01Z
dc.date.issued2023-04-17
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.3389/fmicb.2023.1157544
dc.identifier.issn1664-302X
dc.identifier.urihttps://hdl.handle.net/1843/79421
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofFrontiers in Microbiology
dc.rightsAcesso Aberto
dc.subjectMucosa gastrica
dc.subjectMucosite intestinal
dc.subjectCâncer Tratamento
dc.subject.otherIntestinal inflammation
dc.subject.other5-fluorouracil
dc.subject.otherLactic acid bacteria
dc.subject.otherDNA delivery
dc.subject.othergene therapy
dc.titleGrowth differentiation factor 11 delivered by dairy Lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis
dc.typeArtigo de periódico
local.citation.epage11
local.citation.spage1
local.citation.volume14
local.description.resumoMucositis is an inflammation of the gastrointestinal mucosa that debilitate the quality of life of patients undergoing chemotherapy treatments. In this context, antineoplastic drugs, such as 5-fluorouracil, provokes ulcerations in the intestinal mucosa that lead to the secretion of pro-inflammatory cytokines by activating the NF-κB pathway. Alternative approaches to treat the disease using probiotic strains show promising results, and thereafter, treatments that target the site of inflammation could be further explored. Recently, studies reported that the protein GDF11 has an anti-inflammatory role in several diseases, including in vitro and in vivo results in different experimental models. Hence, this study evaluated the anti-inflammatory effect of GDF11 delivered by Lactococcus lactis strains NCDO2118 and MG1363 in a murine model of intestinal mucositis induced by 5-FU. Our results showed that mice treated with the recombinant lactococci strains presented improved histopathological scores of intestinal damage and a reduction of goblet cell degeneration in the mucosa. It was also observed a significant reduction of neutrophil infiltration in the tissue in comparison to positive control group. Moreover, we observed immunomodulation of inflammatory markers Nfkb1, Nlrp3, Tnf, and upregulation of Il10 in mRNA expression levels in groups treated with recombinant strains that help to partially explain the ameliorative effect in the mucosa. Therefore, the results found in this study suggest that the use of recombinant L. lactis (pExu:gdf11) could offer a potential gene therapy for intestinal mucositis induced by 5-FU.
local.identifier.orcidhttps://orcid.org/0000-0002-6501-9533
local.identifier.orcidhttps://orcid.org/0000-0002-2498-7933
local.identifier.orcidhttps://orcid.org/0000-0002-0237-9398
local.identifier.orcidhttps://orcid.org/0000-0001-7708-3033
local.identifier.orcidhttps://orcid.org/0000-0001-8422-1131
local.identifier.orcidhttps://orcid.org/0000-0002-6903-8184
local.identifier.orcidhttps://orcid.org/0009-0003-4488-6202
local.identifier.orcidhttps://orcid.org/0009-0004-5048-7264
local.identifier.orcidhttps://orcid.org/0000-0002-1835-0303
local.identifier.orcidhttps://orcid.org/0000-0002-5152-1813
local.identifier.orcidhttps://orcid.org/0000-0002-1032-4258
local.identifier.orcidhttps://orcid.org/0000-0003-4967-1414
local.identifier.orcidhttps://orcid.org/0000-0002-4775-2280
local.publisher.countryBrasil
local.publisher.departmentICB - DEPARTAMENTO DE PATOLOGIA
local.publisher.initialsUFMG
local.url.externahttps://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1157544/full

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