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Translating the host-microbiota interaction into risk assessment of invasive aspergillosis

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Detalhes bibliográficos
Resumo:Invasive aspergillosis (IA) is an infection that affects primarily immunocompromised hosts, including hematological patients and stem-cell transplant recipients. Owing to an increasing incidence and despite available antifungal therapy, IA is a leading cause of mortality in these settings. This scenario is worsened by limitations in current diagnostic approaches and evolution of drug resistance in the fungus. The complex interactions between host genetics, environment, and the mucosal immune system have been proposed to shape microbiota composition and function, contributing to lung inflammation and susceptibility to respiratory diseases. Our hypothesis is that disruption of these overlapping layers of immune homeostasis may support the development of infection, particularly in genetically vulnerable individuals. By means of a multidisciplinary approach resorting to complementary technologies, we provide evidence of the intricate contribution of host genetics, the microbiome and the metabolome to susceptibility to IA, and we highlight several biomarkers with diagnostic potential. Collectively, our results are expected to pave the way towards the identification of new targets for personalized diagnostic and therapeutic interventions, and to significantly impact the clinical management of patients suffering from IA.
Autores principais:Gonçalves, Samuel Martins
Assunto:Ciências Médicas
Ano:2017
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
Descrição
Resumo:Invasive aspergillosis (IA) is an infection that affects primarily immunocompromised hosts, including hematological patients and stem-cell transplant recipients. Owing to an increasing incidence and despite available antifungal therapy, IA is a leading cause of mortality in these settings. This scenario is worsened by limitations in current diagnostic approaches and evolution of drug resistance in the fungus. The complex interactions between host genetics, environment, and the mucosal immune system have been proposed to shape microbiota composition and function, contributing to lung inflammation and susceptibility to respiratory diseases. Our hypothesis is that disruption of these overlapping layers of immune homeostasis may support the development of infection, particularly in genetically vulnerable individuals. By means of a multidisciplinary approach resorting to complementary technologies, we provide evidence of the intricate contribution of host genetics, the microbiome and the metabolome to susceptibility to IA, and we highlight several biomarkers with diagnostic potential. Collectively, our results are expected to pave the way towards the identification of new targets for personalized diagnostic and therapeutic interventions, and to significantly impact the clinical management of patients suffering from IA.