Molecule produced in gut can have protective effect against flu, study shows

A molecule produced naturally in the gut can help prevent and even treat influenza, according to a study reported in the journal Gut Microbes by researchers at the State University of Campinas (UNICAMP) in São Paulo state, Brazil, and Pasteur Institut in Lille, France.

Experiments with mice showed a fall in levels of the molecule indole-3-propionic acid (IPA) during infection by influenza virus H3N2.

The infected animals’ IPA was supplemented with a synthetic version of the molecule, after which viral load and lung inflammation were found to have decreased.

“These results are promising and suggest that IPA may in future be used to help prevent or treat infections by influenza virus, which causes major epidemics. However, more research is needed to confirm the findings in humans and to understand how IPA works,” said Marco Vinolo, co-last author of the article and a professor at UNICAMP’s Institute of Biology (IB).

Three layers of data

The study was part of the project “Investigation of the molecular mechanisms involved in the interaction between microbiota-derived metabolites and host cells during inflammation”, which is supported by FAPESP and for which Vinolo is principal investigator.

The above results followed a series of experiments with mice conducted in France and led by Pasteur-Lille’s François Trottein. The data was later analyzed at UNICAMP using bioinformatics tools, and the results of this analysis in turn inspired further experiments with animals at Pasteur.

“We used three layers of data. The first was obtained by metagenomics, showing which bacteria were altered in the gut microbiota after seven days and 14 days of infection. All the DNA of these bacteria was analyzed, whereas this type of study normally analyzes only a piece of one gene that identifies the bacteria. Our analysis showed not only the species of bacteria but also the genes most present and their respective functions,” said Vinicius de Rezende Rodovalho, second author of the article. The study was conducted while he was a postdoctoral researcher at IB-UNICAMP.

Metabolites and clinical markers

The other layers of data were obtained by metabolomics, detecting metabolites secreted by the gut microbiota and clinical markers of the disease such as viral load and inflammation.

“We analyzed these datasets in an integrated manner, building a network of correlations that pointed to an important role for IPA. In further experiments conducted on this basis, we supplemented the animals with a synthetic version of the molecule produced in the laboratory and observed that IPA supplementation reduced viral load and inflammation. The findings suggest that IPA has significant potential as a biomarker of influenza resistance and a target for microbiome-based interventions to treat flu,” Vinolo said.

Metabolizing tryptophan

IPA is produced by gut bacteria when they metabolize tryptophan, an essential amino acid present in whole grains such as soybeans, wheat, corn, barley, rye, oats and sunflower seeds, as well as animal products such as fish, beef, pork, poultry and dairy.

Research by other groups had already shown that IPA supplementation improves metabolic disorders, regulating blood sugar, increasing insulin sensitivity, and inhibiting lipid synthesis and inflammatory factors in the liver.

Other studies have found evidence of the role played by tryptophan and IPA in energy balance and the cardiovascular system, as well as their potential use to help prevent inflammation, obesity, diabetes, cancer, hypertension, neurodegenerative diseases and osteoporosis. 

IPA supplementation

In light of its potential to prevent and combat flu, the researchers have filed with the European Union for a patent on this use of IPA supplementation. Further studies leading to clinical trials are planned. 

“We’re looking at the role of IPA during infection by SARS-CoV-2, the virus that causes COVID-19, and the results have so far been similar. We also want to find out how it functions during bacterial infections. Few studies have been done on the link between gut microbiota and systemic resistance to antibiotics, and IPA’s involvement in this connection could also be a fruitful line of research,” Rodovalho said. 

FAPESP also supported the study by awarding a PhD scholarship to co-author Patrícia Brito Rodrigues, and funding her research internship at Pasteur-Lille.