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Growth differentiation factor 11 delivered by dairy Lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis
Mucositis 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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10149842/ https://www.ncbi.nlm.nih.gov/pubmed/37138633 http://dx.doi.org/10.3389/fmicb.2023.1157544 |
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author | Américo, Monique Ferrary Freitas, Andria dos Santos da Silva, Tales Fernando de Jesus, Luís Cláudio Lima Barroso, Fernanda Alvarenga Lima Campos, Gabriela Munis Santos, Rhayane Cristina Viegas Gomes, Gabriel Camargos Assis, Rafael Ferreira, Ênio Mancha-Agresti, Pamela Laguna, Juliana Guimarães Chatel, Jean-Marc Carvalho, Rodrigo Dias de Oliveira Azevedo, Vasco |
author_facet | Américo, Monique Ferrary Freitas, Andria dos Santos da Silva, Tales Fernando de Jesus, Luís Cláudio Lima Barroso, Fernanda Alvarenga Lima Campos, Gabriela Munis Santos, Rhayane Cristina Viegas Gomes, Gabriel Camargos Assis, Rafael Ferreira, Ênio Mancha-Agresti, Pamela Laguna, Juliana Guimarães Chatel, Jean-Marc Carvalho, Rodrigo Dias de Oliveira Azevedo, Vasco |
author_sort | Américo, Monique Ferrary |
collection | PubMed |
description | Mucositis 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. |
format | Online Article Text |
id | pubmed-10149842 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101498422023-05-02 Growth differentiation factor 11 delivered by dairy Lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis Américo, Monique Ferrary Freitas, Andria dos Santos da Silva, Tales Fernando de Jesus, Luís Cláudio Lima Barroso, Fernanda Alvarenga Lima Campos, Gabriela Munis Santos, Rhayane Cristina Viegas Gomes, Gabriel Camargos Assis, Rafael Ferreira, Ênio Mancha-Agresti, Pamela Laguna, Juliana Guimarães Chatel, Jean-Marc Carvalho, Rodrigo Dias de Oliveira Azevedo, Vasco Front Microbiol Microbiology Mucositis 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. Frontiers Media S.A. 2023-04-17 /pmc/articles/PMC10149842/ /pubmed/37138633 http://dx.doi.org/10.3389/fmicb.2023.1157544 Text en Copyright © 2023 Américo, Freitas, da Silva, de Jesus, Barroso, Campos, Santos, Gomes, Assis, Ferreira, Mancha-Agresti, Laguna, Chatel, Carvalho and Azevedo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Américo, Monique Ferrary Freitas, Andria dos Santos da Silva, Tales Fernando de Jesus, Luís Cláudio Lima Barroso, Fernanda Alvarenga Lima Campos, Gabriela Munis Santos, Rhayane Cristina Viegas Gomes, Gabriel Camargos Assis, Rafael Ferreira, Ênio Mancha-Agresti, Pamela Laguna, Juliana Guimarães Chatel, Jean-Marc Carvalho, Rodrigo Dias de Oliveira Azevedo, Vasco Growth differentiation factor 11 delivered by dairy Lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis |
title | Growth differentiation factor 11 delivered by dairy Lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis |
title_full | Growth differentiation factor 11 delivered by dairy Lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis |
title_fullStr | Growth differentiation factor 11 delivered by dairy Lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis |
title_full_unstemmed | Growth differentiation factor 11 delivered by dairy Lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis |
title_short | Growth differentiation factor 11 delivered by dairy Lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis |
title_sort | growth differentiation factor 11 delivered by dairy lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10149842/ https://www.ncbi.nlm.nih.gov/pubmed/37138633 http://dx.doi.org/10.3389/fmicb.2023.1157544 |
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