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O microbioma e as doenças neurodegenerativas: doença de parkinson
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Nas últimas décadas, o microbioma intestinal tem ganho relevância, emergindo como um
agente importante na saúde do hospedeiro. Tem sido demonstrado que o microbioma
intestinal e seus metabolitos estão envolvidos na modulação de funções gastrointestinais,
pela sua influência na permeabilidade intestinal, função imunológica, mobilidade intestinal,
sensibilidade e atividade do sistema nervoso entérico. Apesar dos recentes
desenvolvimentos, a complexa interação entre a fisiologia do hospedeiro e o microbioma
intestinal, é um tópico que merece a atenção da comunidade científica, no sentido do
desenvolvimento de novas estratégias terapêuticas, particularmente em patologias como a
doença de Parkinson. O microbioma e o cérebro comunicam através de diversas vias, como
sendo o sistema imune, o metabolismo do triptofano, o nervo vago e o sistema nervoso
entérico, envolvendo metabolitos microbianos como os ácidos gordos de cadeia curta ou os
peptidoglicanos. O microbioma intestinal de indivíduos com DP pode apresentar (1) uma
abundância excessiva de um cluster polimicrobial de agentes patógenos oportunistas, (2)
valores reduzidos de baterias produtoras de ácidos gordos de cadeia curta (SCFA) e/ou (3)
valores elevados de agentes microbiais que metabolizam hidratos de carbono (probióticos).
A disbiose intestinal pode comprometer a integridade epitelial e aumentar a permeabilidade
intestinal, permitindo que antigénios provenientes da dieta e sensibilizantes imunológicos
(como as endotoxinas), possam entrar em circulação e promover inflamação e estados
imunes atípicos. Esta inflamação intestinal promove a exacerbação da neuroinflamação, a
disrupção da barreira hematoencefálica e a perda neuronal dopaminérgica na substância
nigra em modelos animais. Este estado inflamatório encontra-se também correlacionado com
a acumulação de -sinucleína intestinal em doentes com DP. Apesar de existir evidência
proveniente de estudos em animais e de estudos clínicos que relacionam o microbioma numa
variedade de doenças neurológicas, neurodegenerativas e psiquiátricas, esta área de estudo
encontra-se ainda no seu início, sendo necessário prudência na interpretação dos resultados.
Revela-se urgente desenvolver formulações de probióticos ou tratamentos de transferência
fecal microbiana mais eficientes, estandardizar e reduzir a variabilidade na resposta do
doente. Será também importante os futuros investigadores distanciarem-se de estudos
correlacionais, direcionando a investigação para estudos longitudinais prospetivos e análises
de causalidade realizados em maior escala.
In the past decades, the gut microbiome has gain importance, emerging as an important agent in the host health. It has been proved that gut microbiome and its metabolites are involved in the modulation of gastrointestinal functions through its influence in the intestinal permeability, immunological function, intestinal mobility, and enteric nervous system activity. Despite recent developments, the complex interaction between the host physiology and the gut microbiome is a subject that deserves the focus of the scientific community to develop new therapeutic strategies, particularly in neurodegenerative diseases like Parkinson’s. The gut microbiome and the human brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short chain fat acids and peptidoglycans. The gut microbiome of patients with Parkinson’s disease can present with (1) an overabundance of a polymicrobial cluster of opportunistic pathogens, (2) reduced levels of SCFA-producing bacteria, and/or (3) elevated levels of carbohydrate metabolizers commonly known as probiotics. Gut dysbiosis can compromise the epithelial barrier and increase intestinal permeability allowing that antigens from diet and immunological stimulating bacterial products enter circulation and promote inflammation and atypic immune states. This inflammation promotes the exacerbation of neuroinflammation, blood-brain barrier disruption and neuronal dopaminergic loss in substancia nigra (animal models). Furthermore, this inflammatory state is correlated with the accumulation of intestinal alpha-synucleín in Parkinson’s patients. Despite the evidence from animal studies and clinical trials that implicate the microbiome in a variety of neurological and neurodegenerative diseases, this field of study is still taking its first steps. Precaution is needed regarding the interpretation of results. Moreover, it is urgent the development of more standardized and efficient treatments, as probiotics formulas or oral capsules in fecal microbial transplant, reducing the response variability and increasing the adherence in patients. It will be important for the field to move away from just correlative analysis towards prospective longitudinal studies, causative analyses, and larger scale trials of potential therapeutic approaches.
In the past decades, the gut microbiome has gain importance, emerging as an important agent in the host health. It has been proved that gut microbiome and its metabolites are involved in the modulation of gastrointestinal functions through its influence in the intestinal permeability, immunological function, intestinal mobility, and enteric nervous system activity. Despite recent developments, the complex interaction between the host physiology and the gut microbiome is a subject that deserves the focus of the scientific community to develop new therapeutic strategies, particularly in neurodegenerative diseases like Parkinson’s. The gut microbiome and the human brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short chain fat acids and peptidoglycans. The gut microbiome of patients with Parkinson’s disease can present with (1) an overabundance of a polymicrobial cluster of opportunistic pathogens, (2) reduced levels of SCFA-producing bacteria, and/or (3) elevated levels of carbohydrate metabolizers commonly known as probiotics. Gut dysbiosis can compromise the epithelial barrier and increase intestinal permeability allowing that antigens from diet and immunological stimulating bacterial products enter circulation and promote inflammation and atypic immune states. This inflammation promotes the exacerbation of neuroinflammation, blood-brain barrier disruption and neuronal dopaminergic loss in substancia nigra (animal models). Furthermore, this inflammatory state is correlated with the accumulation of intestinal alpha-synucleín in Parkinson’s patients. Despite the evidence from animal studies and clinical trials that implicate the microbiome in a variety of neurological and neurodegenerative diseases, this field of study is still taking its first steps. Precaution is needed regarding the interpretation of results. Moreover, it is urgent the development of more standardized and efficient treatments, as probiotics formulas or oral capsules in fecal microbial transplant, reducing the response variability and increasing the adherence in patients. It will be important for the field to move away from just correlative analysis towards prospective longitudinal studies, causative analyses, and larger scale trials of potential therapeutic approaches.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2020, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Microbiome Microbiota Intestinal inflammation Neurodegenerative diseases Parkinson’s disease Mestrado integrado - 2020