Dermatite de contato alérgica e seu papel na quebra da homeostas intestinal
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Data
2023-03-16
Autores
Mendes, Eduardo [UNIFESP]
Orientadores
Ferreira, Caroline Marcantonio [UNIFESP]
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
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Resumo
Objetivo: O presente trabalho avaliou as alterações resultantes da dermatite de contato alérgica (DCA) no intestino, assim como a influência e a administração de um probiótico via gástrica, nessas possíveis alterações intestinais, causadas por essa doença de pele. Métodos: Utilizamos camundongos Balb/c fêmeas que foram distribuídos em quatro grupos experimentais, Basal, Controle, OXA e OXA/BL. Primeiramente, induzimos a DCA com duas aplicações de Oxazolona na pele ou seu veículo. Vinte e quatro horas após a última aplicação de Oxazolona, analisamos a morfológica da pele, microbiota intestinal, ácidos graxos de cadeia curta, citocinas, permeabilidade intestinal e alterações morfológicas, posteriormente avaliamos se o uso do probiótico Bifidobacterium longum subsp. longum BB536, administrado por via gavagem 10 dias antes da indução da DCA até 1 dia antes do desafio, resultando em 17 dias de tratamento, que seria efetivo na prevenção ou inibição das possíveis alterações intestinais. Resultado: Os dados mostram que o modelo DCA induzida por Oxazolona causa alterações na pele como aumento da espessura da pele, da derme, epiderme e infiltrado de células inflamatórias. Além disso, as alterações de pele induzidas por esse modelo também afetam o intestino. A primeira observação foi que a composição da microbiota intestinal foi afetada pela dermatite. O aumento da expressão de genes relacionados a citocinas inflamatórias como a IL-6 e diminuição de genes, relacionados a citocina anti-inflamatória, a IL-10, bem como diminuição da expressão de genes envolvidos com a permeabilidade intestinal Tjp1 e ATHO1. A avaliação da morfologia intestinal, mostra que a dermatite afeta principalmente o cólon distal aumentando a espessura da musculatura total e da mucosa. Ao tratar esses animais com probiótico, a fim de evitar essas alterações intestinais causada pela doença de pele, observamos que houve alteração da composição da microbiota intestinal e aumento da produção de um ácido graxo de cadeia curta, o acetato, aumento da expressão de citocina anti-inflamatória IL-10 e redução da IL-6. Houve também melhora da expressão de genes relacionadas a melhora da barreira intestinal, Tjp1 e ATHO1. Quando avaliado a morfologia do intestino, o tratamento com probiótico não promove melhora das alterações morfológicas, causada pela DCA. Por fim, avaliamos se o probiótico utilizado para prevenir ou atenuar alterações intestinais poderia afetar também a pele. Observamos que o tratamento com probiótico afetou apenas a espessura de pele. Conclusão: A DCA promoveu alterações morfológicas, moleculares e de micro-organismos no intestino, possivelmente tornando o ambiente propicio para o desenvolvimento de patologias intestinais. Entretanto, o tratamento com probiótico reverteu algumas das alterações promovidas pela DCA, indicando que o tratamento com essas bactérias, benéficas, pode ser uma importante ferramenta estratégica para prevenir o desenvolvimento de doenças inflamatórias intestinais a longo prazo, em pacientes com doença de pele.
Objective: The present study evaluated the alterations resulting from allergic contact dermatitis (ACD) in the intestine, as well as the influence of the administration of a probiotic via the gastric route, on these possible intestinal alterations caused by this skin disease. Methods: We used female Balb/c mice that were distributed into four experimental groups, Basal, Control, OXA and OXA/BL. First, we induce DCA with two applications of oxazolone to the skin or its vehicle. Twenty-four hours after the last application of oxazolone, we analyzed the morphology of the skin, intestinal microbiota, short-chain fatty acids, cytokines, intestinal permeability and morphological changes, evaluating whether the use of the probiotic Bifidobacterium longum subsp. longum BB536, administered via gavage 10 days before the induction of DCA until 1 day before the challenge resulted in 17 days of treatment that would effectively prevent or inhibit possible intestinal changes. Result: The data demonstrated that the oxazolone-induced DCA model causes significant changes in the skin, such as increased thickness of the skin, dermis, epidermis and infiltration of inflammatory cells. Furthermore, the skin changes induced by this model also affect the gut. The first observation was that the composition of the intestinal microbiota is affected by dermatitis. Increased expression of genes, related to inflammatory cytokines, such as IL-6 and decreased expression of genes related to anti-inflammatory cytokine, IL-10, as well as decreased expression of genes involved with intestinal permeability Tjp1 and ATHO1. The evaluation of intestinal morphology demonstrates that dermatitis mainly affects the distal colon, increasing the thickness of the total musculature and mucosa. When treating these animals with probiotics, to avoid these intestinal alterations, caused by the skin disease, we observed that there was a change in the composition of the intestinal microbiota and an increase in the production of a short-chain fatty acid, acetate, an increase in the expression of anti-inflammatory cytokines -inflammatory IL-10 and IL-6 reduction. There was also an improvement in the expression of genes, related to the improvement of the intestinal barrier, Tjp1 and ATHO1. When evaluating the morphology of the intestine treatment with probiotics, does not improve the morphological changes, caused by ACD. Finally, we evaluated whether the probiotic used to prevent or mitigate intestinal changes could also affect the skin We also observed that the probiotic treatment affected only the thickness of the skin. Conclusion: DCA promoted morphological, molecular and microorganism changes in the intestine, possibly making the environment conducive to the development of intestinal pathologies. However, treatment with probiotics reversed some of the changes promoted by DCA, indicating that treatment with these beneficial bacteria may be an important strategic tool to prevent the development of long-term inflammatory bowel disease in patients with skin disease.
Objective: The present study evaluated the alterations resulting from allergic contact dermatitis (ACD) in the intestine, as well as the influence of the administration of a probiotic via the gastric route, on these possible intestinal alterations caused by this skin disease. Methods: We used female Balb/c mice that were distributed into four experimental groups, Basal, Control, OXA and OXA/BL. First, we induce DCA with two applications of oxazolone to the skin or its vehicle. Twenty-four hours after the last application of oxazolone, we analyzed the morphology of the skin, intestinal microbiota, short-chain fatty acids, cytokines, intestinal permeability and morphological changes, evaluating whether the use of the probiotic Bifidobacterium longum subsp. longum BB536, administered via gavage 10 days before the induction of DCA until 1 day before the challenge resulted in 17 days of treatment that would effectively prevent or inhibit possible intestinal changes. Result: The data demonstrated that the oxazolone-induced DCA model causes significant changes in the skin, such as increased thickness of the skin, dermis, epidermis and infiltration of inflammatory cells. Furthermore, the skin changes induced by this model also affect the gut. The first observation was that the composition of the intestinal microbiota is affected by dermatitis. Increased expression of genes, related to inflammatory cytokines, such as IL-6 and decreased expression of genes related to anti-inflammatory cytokine, IL-10, as well as decreased expression of genes involved with intestinal permeability Tjp1 and ATHO1. The evaluation of intestinal morphology demonstrates that dermatitis mainly affects the distal colon, increasing the thickness of the total musculature and mucosa. When treating these animals with probiotics, to avoid these intestinal alterations, caused by the skin disease, we observed that there was a change in the composition of the intestinal microbiota and an increase in the production of a short-chain fatty acid, acetate, an increase in the expression of anti-inflammatory cytokines -inflammatory IL-10 and IL-6 reduction. There was also an improvement in the expression of genes, related to the improvement of the intestinal barrier, Tjp1 and ATHO1. When evaluating the morphology of the intestine treatment with probiotics, does not improve the morphological changes, caused by ACD. Finally, we evaluated whether the probiotic used to prevent or mitigate intestinal changes could also affect the skin We also observed that the probiotic treatment affected only the thickness of the skin. Conclusion: DCA promoted morphological, molecular and microorganism changes in the intestine, possibly making the environment conducive to the development of intestinal pathologies. However, treatment with probiotics reversed some of the changes promoted by DCA, indicating that treatment with these beneficial bacteria may be an important strategic tool to prevent the development of long-term inflammatory bowel disease in patients with skin disease.