| Autor: |
Juliana Guimarães Laguna, Andria dos Santos Freitas, Fernanda Alvarenga Lima Barroso, Luís Cláudio Lima De Jesus, Octávio Augusto Greco Gomes De Vasconcelos, Ludmila Silva Quaresma, Monique Ferrary Américo, Gabriela Munis Campos, Rafael de Assis Glória, Joyce da Cruz Ferraz Dutra, Tales Fernando Da Silva, Kátia Duarte Vital, Simone O. Fernandes, Ramon O. Souza, Flaviano dos Santos Martins, Enio Ferreira, Túlio Marcos Santos, Alexander Birbrair, Marcos Felipe Andrade De Oliveira, Ana Maria Caetano Faria, Rodrigo Dias de Oliveira Carvalho, Franco Maria Venanzi, Yves Le Loir, Gwénaël Jan, Éric Guédon, Vasco Ariston de Carvalho Azevedo |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Frontiers in Microbiology, Vol 15 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1664-302X |
| DOI: |
10.3389/fmicb.2024.1309160 |
| Popis: |
Introduction and objectivep62 is a human multifunctional adaptor protein involved in key cellular processes such as tissue homeostasis, inflammation, and cancer. It acts as a negative regulator of inflammasome complexes. It may thus be considered a good candidate for therapeutic use in inflammatory bowel diseases (IBD), such as colitis. Probiotics, including recombinant probiotic strains producing or delivering therapeutic biomolecules to the host mucosal surfaces, could help prevent and mitigate chronic intestinal inflammation. The objective of the present study was to combine the intrinsic immunomodulatory properties of the probiotic Lactococcus lactis NCDO2118 with its ability to deliver health-promoting molecules to enhance its protective and preventive effects in the context of ulcerative colitis (UC).Material and methodsThis study was realized in vivo in which mice were supplemented with the recombinant strain. The intestinal barrier function was analyzed by monitoring permeability, secretory IgA total levels, mucin expression, and tight junction genes. Its integrity was evaluated by histological analyses. Regarding inflammation, colonic cytokine levels, myeloperoxidase (MPO), and expression of key genes were monitored. The intestinal microbiota composition was investigated using 16S rRNA Gene Sequencing.Results and discussionNo protective effect of L. lactis NCDO2118 pExu:p62 was observed regarding mice clinical parameters compared to the L. lactis NCDO2118 pExu: empty. However, the recombinant strain, expressing p62, increased the goblet cell counts, upregulated Muc2 gene expression in the colon, and downregulated pro-inflammatory cytokines Tnf and Ifng when compared to L. lactis NCDO2118 pExu: empty and inflamed groups. This recombinant strain also decreased colonic MPO activity. No difference in the intestinal microbiota was observed between all treatments. Altogether, our results show that recombinant L. lactis NCDO2118 delivering p62 protein protected the intestinal mucosa and mitigated inflammatory damages caused by dextran sodium sulfate (DSS). We thus suggest that p62 may constitute part of a therapeutic approach targeting inflammation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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