A study reveals that a gut-derived molecule, indole-3-propionic acid (IPA), may be able to treat influenza by reducing viral activity and inflammation in mice, with human trials planned to confirm these results.
Researchers from the State University of Campinas in Brazil and the Pasteur Institute in Lille, France, conducted experiments in mice and found that administering a specific substance reduced both viral load and inflammation in influenza-infected animals. virus.
According to a study published in the journal Intestinal bacteriaResearchers from the State University of Campinas (UNICAMP) in São Paulo, Brazil, and the Pasteur Institute in Lille, France, have discovered that a molecule found naturally in the gut can prevent and even treat influenza.
In experiments with mice, levels of the molecule indole-3-propionic acid decreased. acid (IPA) during influenza virus H3N2 infection.
When they supplemented the IPAs of infected animals with a synthetic version of the molecule, they found that viral load and lung inflammation were reduced.
“These results are promising and suggest that in future IPA could be used to prevent or treat infections caused by influenza viruses, which cause large epidemics. However, further studies are needed to confirm the results in humans and understand how IPA works,” said Marco Vignolo, co-author of the paper and professor at the UNICAMP Institute of Biology (IB).
This study was part of a project “Investigating the molecular mechanisms involved in the interaction between microbial metabolites and host cells during inflammation”The research was supported by FAPESP and Vinolo is the principal investigator.
The results above are the result of a series of experiments on mice conducted in France, led by François Trotin at Pasteur-Lille. The data were then analysed at UNICAMP using bioinformatics tools, and the results of this analysis prompted further experiments on animals at Pasteur.
“We used three layers of data. The first data was obtained by metagenomics, which shows which bacteria changed in the gut microbiome on days 7 and 14 after infection. DNA While this type of study typically only analyses a portion of the genes that identify a bacterium, this analysis analysed a portion of the bacterial genome. seed “We not only reveal the bacterial genome, but also the most abundant genes and their respective functions,” said Vinicius de Rezende Rodováhlo, second author of the paper, who carried out the research while he was a postdoctoral researcher at IB-UNICAMP.
Other layers of data will be obtained through metabolomics, detecting metabolites secreted by the gut microbiota and clinical markers of disease, such as viral load and inflammation.
“We performed an integrated analysis of these datasets and built a network of correlations suggesting a key role for IPA. Based on this, we conducted further experiments, supplementing animals with a synthetic version of the molecule made in the lab and observed that IPA supplementation reduced viral load and inflammation. These results suggest that IPA has great potential as a biomarker of influenza resistance and as a target for microbiome-based interventions for influenza treatment,” Vignolo said.
supplement
IPA is produced when gut bacteria metabolize tryptophan, an essential amino acid found in whole grains such as soybeans, wheat, corn, barley, rye, oats and sunflower seeds, as well as animal foods such as fish, beef, pork, chicken and dairy products.
Other studies have shown that IPA supplements improve metabolic disorders, regulate blood sugar levels, Insulin It increases sensitivity and inhibits lipid synthesis and inflammatory factors in the liver.
Other studies have found evidence of a role that tryptophan and IPA play in energy balance and the cardiovascular system, and may help prevent inflammation, obesity, diabetes, cancer, hypertension, neurodegenerative diseases, and osteoporosis.
Given its potential effectiveness in preventing and treating influenza, the researchers have applied for a patent in the European Union for this use of IPA supplements. Further studies leading to clinical trials are planned.
“We are studying the role of IPA during infection. SARS-CoV-2causing a virus COVID-19“We have been studying the relationship between the gut microbiota and systemic resistance to antibiotics, and so far the results are similar. We also want to understand how it functions during bacterial infections. Little research has been done on the link between the gut microbiota and systemic resistance to antibiotics, and the involvement of IPA in this relationship could also be a fruitful area of research,” said Rodovário.
Reference: “Shotgun metagenomics and whole-body targeted metabolomics reveal indole-3-propionic acid as a protective gut microbial metabolite against influenza infection”, Séverine Heumel, Vinícius de Rezende Rodovalho, Charlotte Urien, Florian Specque, Patrícia Brito Rodrigues, Cyril Robil, Lou Delval, Valentin Sencio, Amandine Descat, Lucie Deruyter, Stéphanie Ferreira, Marina Gomes Machado, Adeline Barthelemy, Fabiola Silva Angulo, Joel. T Haas, Jean François Goosens, Isabelle Wolowczuk, Corinne Grangette, Yves Rouillé, Ghjuvan Grimaud, Marie Lenski, Benjamin Hennart, Marco Aurélio Ramirez Vinolo, François Trottein, 2024 3 On the 6th of this month, Intestinal bacteria.
Translation: 10.1080/19490976.2024.2325067
FAPESP also supported the research by awarding co-author Patricia Brito Rodríguez a PhD scholarship and funding a research internship at Pasteur Lille.
