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A relação entre o sistema nervoso e a microbiota entérica é um tópico que tem gerado bastante atenção no campo das neurociências. A microbiota entérica corresponde ao conjunto de microrganismos que habitam o trato digestivo dos animais. A colonização intestinal ocorre, na grande maioria, durante a passagem do bebé pelo canal do parto, onde é exposto à microbiota da mãe. Assim, a constituição da microbiota entérica varia consoante o tipo de parto e consoante fatores como o modo de amamentação, o genótipo, o país e região do hospedeiro, o uso de antibióticos, prebióticos e probióticos. A microbiota entérica nos primeiros dias de vida é pouco diversificada e instável; atingindo a idade adulta ela mantém-se relativamente estável ao longo do tempo e torna-se única e característica de cada individuo. Quando o hospedeiro é exposto a agentes externos como as alterações da dieta ou o uso de antibióticos a microbiota entérica, que se encontra em simbiose com o hospedeiro, sofre alterações. Contudo, ela apresenta uma grande capacidade de resistir e restaurar o seu núcleo microbiano. Apesar da resiliência da microbiota, esta pode sofrer um fenómeno de disbiose, que por sua vez, se correlaciona com a elevada prevalência de patologias crónicas e neurodegenerativas, no hospedeiro.
Em particular, a microbiota entérica estabelece uma relação bidirecional com o sistema nervoso central (SNC). Este dinamismo implica efeitos em diversos mecanismos, como a alteração da permeabilidade intestinal, que permite a passagem de microrganismos e dos seus metabolitos neuroativos para a corrente sanguínea que irão modular o SNC, e a modulação do nervo vago e do eixo hipotálamo-hipófise.
Neste sentido, a microbiota entérica influencia o desenvolvimento e a manutenção do equilíbrio dos órgãos e tecidos e o seu papel é importante na manutenção da saúde cerebral, pois através das vias neuro-endócrinas e imunológicas este ecossistema desencadeia a modulação do sistema nervoso. Por este motivo têm emergido trabalhos centrados no estudo do impacto da microbiota entérica na saúde neurológica através de estudos quer em modelos pré-clínicos quer em humanos. Nestes estudos a microbiota entérica é manipulada através da administração de probióticos, prebióticos ou antibióticos. Modelos animal livres de germes são frequentemente usados neste tipo de estudos.
Alguns destes estudos permitiram concluir que a disbiose entérica, provocada pela administração de antibióticos ou pela infeção entérica, propicia comportamentos de ansiedade em modelos animais. Paralelamente verificou-se que os animais livres de germes se apresentam menos ansiosos quando sujeitos a estímulo indutor de stresse, apesar de terem um elevado nível de corticosterona e de Hormona adrenocorticotrófica (ACTH) e défices na memória não-espacial e na memória de trabalho. Relativamente à doença de Parkinson, alguns autores verificaram que o risco de desenvolver esta patologia é inferior nos pacientes submetidos a vagotomia total, sugerindo uma atuação do nervo vago na patogénese do Parkinson; outros comprovaram existir um agravamento dos sintomas motores com a disbiose entérica.
Resultados de alguns trabalhos sugerem também a existência de uma correlação entre a disbiose entérica e a progressão da doença de Alzheimer.
The relationship between the nervous system and the enteric microbiota is a topic that has generated a lot of attention in the field of neurosciences. The enteric microbiota corresponds to the set of microorganisms that colonize the digestive tract of the animals. Most intestinal colonization occurs during the passage of the baby through the birth canal, where it is exposed to the mother's microbiota. Thus, the constitution of the enteric microbiota varies according to the type of delivery and depending on factors such as the mode of breastfeeding, the genotype, the host country and region, the use of antibiotics, prebiotics and probiotics. The enteric microbiota in the first days of life is little diversified and unstable; reaching adulthood it remains stable over time and becomes unique and characteristic of each individual. When the host is exposed to external agents such as diet changes or the use of antibiotics, the enteric microbiota, which is in symbiosis with the host, undergoes changes in its dynamism. However, it has a great ability to resist and restore its microbial nucleus. Despite the resilience of the microbiota, it can undergo a phenomenon of dysbiosis, which in turn, correlates with the high prevalence of chronic and neurodegenerative pathologies in the host. In particular, the enteric microbiota establishes a bidirectional relationship with the central nervous system (CNS). This dynamism involves several mechanisms, from the change in intestinal permeability, that allows the passage of microorganisms and their neuroactive metabolites to the bloodstream that will modulate the CNS, to the modulation of the action of the vagus nerve and the hypothalamic-pituitary axis. In this sense, the enteric microbiota influences the development and maintenance of the balance of organs and tissues and their role is important in maintaining cerebral health, since through the neuro-endocrine and immunological pathways this ecosystem modulates the nervous system. For this reason, research has been focused on the study of the impact of the enteric microbiota on neurological health through the use of preclinical models and also of studies in in humans. In these studies, the enteric microbiota is manipulated through the administration of probiotics, prebiotics or antibiotics. Germ-free animal model is also frequently used in these investigations. Some of these studies allowed us to conclude that enteric dysbiosis, caused by the administration of antibiotics or by enteric infection, leads to anxious behaviours in conventional animals. At the same time, it was found that the germ-free animals are less anxious, despite having high level of corticosterone and ACTH and non-spatial deficits in spatial memory and working memory. Concerning Parkinson's disease, some authors found that the risk of developing the disease is lower in patients undergoing total vagotomy, suggesting a role of the vagus nerve role in the Parkinson’s disease pathogenesis; others showed a correlation between the worsening of motor symptoms and enteric dysbiosis. Finally, some data, although scarce, point to the existence of a correlation between enteric dysbiosis and the progression of Alzheimer's disease.
The relationship between the nervous system and the enteric microbiota is a topic that has generated a lot of attention in the field of neurosciences. The enteric microbiota corresponds to the set of microorganisms that colonize the digestive tract of the animals. Most intestinal colonization occurs during the passage of the baby through the birth canal, where it is exposed to the mother's microbiota. Thus, the constitution of the enteric microbiota varies according to the type of delivery and depending on factors such as the mode of breastfeeding, the genotype, the host country and region, the use of antibiotics, prebiotics and probiotics. The enteric microbiota in the first days of life is little diversified and unstable; reaching adulthood it remains stable over time and becomes unique and characteristic of each individual. When the host is exposed to external agents such as diet changes or the use of antibiotics, the enteric microbiota, which is in symbiosis with the host, undergoes changes in its dynamism. However, it has a great ability to resist and restore its microbial nucleus. Despite the resilience of the microbiota, it can undergo a phenomenon of dysbiosis, which in turn, correlates with the high prevalence of chronic and neurodegenerative pathologies in the host. In particular, the enteric microbiota establishes a bidirectional relationship with the central nervous system (CNS). This dynamism involves several mechanisms, from the change in intestinal permeability, that allows the passage of microorganisms and their neuroactive metabolites to the bloodstream that will modulate the CNS, to the modulation of the action of the vagus nerve and the hypothalamic-pituitary axis. In this sense, the enteric microbiota influences the development and maintenance of the balance of organs and tissues and their role is important in maintaining cerebral health, since through the neuro-endocrine and immunological pathways this ecosystem modulates the nervous system. For this reason, research has been focused on the study of the impact of the enteric microbiota on neurological health through the use of preclinical models and also of studies in in humans. In these studies, the enteric microbiota is manipulated through the administration of probiotics, prebiotics or antibiotics. Germ-free animal model is also frequently used in these investigations. Some of these studies allowed us to conclude that enteric dysbiosis, caused by the administration of antibiotics or by enteric infection, leads to anxious behaviours in conventional animals. At the same time, it was found that the germ-free animals are less anxious, despite having high level of corticosterone and ACTH and non-spatial deficits in spatial memory and working memory. Concerning Parkinson's disease, some authors found that the risk of developing the disease is lower in patients undergoing total vagotomy, suggesting a role of the vagus nerve role in the Parkinson’s disease pathogenesis; others showed a correlation between the worsening of motor symptoms and enteric dysbiosis. Finally, some data, although scarce, point to the existence of a correlation between enteric dysbiosis and the progression of Alzheimer's disease.
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Keywords
Disbiose Entérica Distúrbios Neurodegenerativos Microbiota Entérica Saúde Cerebral