Molécula produzida no intestino pode ter efeito protetor contra gripe, indica estudo

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Tratamento de influenza em camundongos sem IPA (esquerda) e com IPA (direita)

Uma molécula produzida naturalmente no intestino pode ajudar a prevenir e tratar a gripe. É o que aponta um estudo publicado na revista Gut Microbes por pesquisadores da Universidade Estadual de Campinas (Unicamp) e do Instituto Pasteur de Lille, na França.

Experimentos com camundongos mostraram uma queda nos níveis da molécula conhecida como ácido indol-3-propiônico (IPA, na sigla em inglês) durante a infecção pelo vírus Influenza, variante H3N2.

Ao suplementar os animais infectados com uma versão sintética do IPA, os pesquisadores observaram uma redução na carga viral e na inflamação dos pulmões.

“Esses resultados são promissores e sugerem que o IPA, no futuro, poderá ser usado para ajudar a prevenir ou tratar a infecção pelo vírus influenza, responsável por grandes epidemias. No entanto, mais estudos são necessários para confirmar esses achados em humanos e para entender melhor como o IPA funciona”, esclarece Marco Vinolo, professor do Instituto de Biologia (IB) da Unicamp.

O estudo ocorreu no âmbito do projeto “Análise dos mecanismos moleculares envolvidos na interação de metabólitos da microbiota e células do hospedeiro durante a inflamação”, coordenado por Vinolo e apoiado pela Fapesp.

Os resultados foram possíveis depois de uma série de experimentos com camundongos conduzidos na França, sob coordenação de François Trottein, do Pasteur. Posteriormente, foram feitas análises usando ferramentas de bioinformática, na Unicamp, que inspiraram novos experimentos com animais no Instituto Pasteur.

“Usamos três camadas de dados: a primeira foi a de metagenômica, que mostrou quais bactérias estavam alteradas no intestino depois de 7 e 14 dias da infecção. Foi avaliado todo o DNA desses microrganismos, quando nesse tipo de estudo normalmente só se avalia um trecho de um gene que identifica as bactérias. Nossa análise mostra não apenas as espécies bacterianas, mas os genes mais presentes e suas respectivas funções”, explica Vinicius de Rezende Rodovalho, um dos autores principais do trabalho, realizado durante seu pós-doutorado no IB-Unicamp.

As outras camadas de dados foram obtidas a partir das técnicas de metabolômica, que avaliaram os metabólitos secretados pela microbiota presente no intestino e os marcadores clínicos da doença, como carga viral e marcadores inflamatórios.

“Analisamos esses dados de forma integrada, construindo uma rede de correlações que mostrou um importante papel para o IPA. A partir disso, novos experimentos foram realizados. Neles, suplementamos os animais com uma versão sintética da molécula, produzida em laboratório, o que diminuiu a carga viral e a inflamação. Isso traz um grande potencial para uma nova terapêutica da gripe”, conta Vinolo.

Suplemento

O IPA é produzido por bactérias presentes na microbiota intestinal a partir do processamento do triptofano, um aminoácido essencial presente em alimentos como soja, trigo, milho, cevada, centeio, girassol, peixe e carne.

Trabalhos de outros grupos já haviam mostrado efeitos do IPA para a melhora de distúrbios metabólicos, regulando a glicemia, aumentando a sensibilidade à insulina e inibindo a síntese de lipídios e fatores inflamatórios no fígado.

Outros estudos mostravam ainda evidências da ação do triptofano e do IPA no equilíbrio energético e no sistema cardiovascular, assim como potencial na prevenção de inflamação, obesidade, diabetes, doenças cardiovasculares, câncer, hipertensão, doenças neurodegenerativas e osteoporose.

Por conta do potencial do IPA como um suplemento no combate e prevenção da gripe, os pesquisadores depositaram uma patente na União Europeia para esse uso do ácido indol-3-propiônico. A expectativa é realizar novos estudos que possam subsidiar testes clínicos no futuro.

“Estamos avaliando o papel do IPA durante a infecção pelo SARS-CoV-2, causador da Covid-19, e os resultados, até agora, são parecidos. Queremos testar ainda como ele atua em infecções bacterianas. Existem poucos estudos mostrando como a microbiota intestinal atua na resistência sistêmica a antibióticos e esse pode ser um caminho”, encerra Rodovalho.

O estudo teve ainda apoio da Fapesp por meio de bolsa de doutorado para Patrícia Brito Rodrigues, com estágio no Instituto Pasteur de Lille, na França.

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