This is what a study developed in partnership between Unicamp and PUC-RS and recently published in the journal “Nature Communication” shows.
Researchers from Unicamp, in partnership with PUC-RS, published in July, in the journal Kind Communication, work in which they evaluated the effect of short-chain fatty acids on the development of viral infection by Respiratory Syncytial Virus (RSV) in mice. Preclinical data demonstrated that supplementing these animals with diets enriched with soluble fiber or with sodium acetate added to drinking water protected them against RSV infection, significantly reducing weight loss, viral load and cellular infiltrate in the lungs. during illness.
The work carried out by researchers from both universities began in 2013 through the collaboration of the group coordinated by professor Marco Aurélio Ramirez Vinolo – from the Department of Genetics, Evolution, Microbiology and Immunology, from the Institute of Biology (IB) at Unicamp – with the group from the Pontifical Catholic University (PUC) of RS, led by professor Ana Paula Duarte de Souza, specialized in viruses, joined by researchers from Unicamp Maria Teresa Pedrosa Silva Clerici, from the Faculty of Food Engineering (FEA), who collaborated with the development of diets for animals; José Luiz Proença-Módena, from IB, specialist in virology; and Hosana Gomes Rodrigues, from the Faculty of Applied Sciences, based in Limeira (FCA), who, in addition to being a specialist in inflammation, helped with the quantification of short-chain fatty acids.
Mention should also be made of the participation of postgraduate students from Unicamp, including doctoral student José Luís Fachi and master's student Laís Passarielo Pral, both from IB at Unicamp, and doctoral student Krist Helen Antunes from PUCRS, co-supervised by Marco Aurélio.
The professor, coordinator of the project, explains that the work was proposed because at the time there was epidemiological data that the intake of foods with a high fiber content could generate protection in children in relation to respiratory infections. At the same time, a study was published showing, in animal models, that the consumption of fiber could protect them against the development of asthma, also an inflammatory respiratory disease. By the way, he says: “We came to the conclusion that it would be worth checking whether Respiratory Syncytial Virus (RSV) infection could somehow be prevented or mitigated. Infection with this virus is very common in newborn children and up to three years of age, with the disease manifesting itself in around 70% and in some of them progressing to a serious condition of respiratory inflammation called bronchiolitis, which can even cause the death". This disease, characterized by vast inflammation and edema of the airways, causes an increase in mucus production and necrosis of lung epithelial cells specifically in the bronchi. In 2017, an increase in serious cases of RSV-infected children sent to the ICU was recorded in São Paulo, which drew the attention of the medical and scientific community to the need to develop therapies for the treatment and containment of this disease. There is no treatment for this infection other than the use of medication to alleviate symptoms such as fever, body pain, breathing difficulties, as is the case with the flu.
The study
In the study, researchers basically used laboratory animals to test the hypothesis that fibers could have a beneficial effect against the virus. Mice were fed a previously formulated diet rich in fiber. For comparative purposes, another group received a low-fiber diet. The initial objective was to verify whether the research was justified and should continue in the direction of the proposed hypothesis.
After three weeks on the diet, all animals were infected so that it could be seen how they would respond to the infection. It was observed that those who ate a high-fiber diet had fewer viruses in their lungs after five days. More than that, these animals did not present a picture of lung inflammation, unlike those that had ingested a low fiber content, in which there was great inflammation in the lungs. This first result showed that fiber consumption protects the animal against RSV infection.
Given this, the researchers set out to unravel the mechanism that leads fiber to promote protection against this type of infection. It was already known that these fibers led to the formation of compounds naturally generated by the intestinal microbiota, the so-called short-chain fatty acids, common to all human beings, but whose concentrations can vary and depend on several factors, including type of diet and conditions. metabolism of different organisms. This variation in concentration can make the individual more or less susceptible to various types of diseases, although it was not yet known how these compounds acted on the infection caused by the virus in question.
Experiments were then carried out to prove that protection resulted from the action of compounds naturally generated by the microbiota, short-chain fatty acids. To this end, the animals' microbiota was eliminated with the application of antibiotics. The protective effect effectively ceased, but it returned when the animals received short-chain fatty acids orally. This confirmed the hypothesis that these fatty acids produced by the intestinal microbiota are absorbed by the organ and act on lung cells, reducing the amount of viruses.
For Marco Aurélio, the interesting thing is that other experiments carried out by the team, such as the administration of short-chain fatty acids to animals, either through drinking water containing sodium acetate or through inhalation of the same solution, produced the same protective effect. This finding led researchers to think that this treatment might also work in humans.
The research group is also carrying out an initial analysis in humans, which consists of verifying whether there is a correlation between the amounts of short-chain fatty acids produced in the body and the intensity of RSV infection. This research is being carried out with children already affected by the infection and treated in a hospital in Porto Alegre. They measure the concentrations of endogenous fatty acids. Still preliminary results indicate that the greater the amount of them in the feces, the lower the chance of them developing a serious infection and the shorter the hospitalization time.
In summary
In work with animals, it was found that the administration of fibers, which lead to the generation of short-chain fatty acids in the intestine, or even directly of these compounds, contributes to protection during infection by the RSV virus, as shown in the figure.
Figure sent by the interviewee
In work with animals, a beneficial effect of the administration of short-chain fatty acids was observed when they were administered before infection (prevention strategy), as well as in recently infected animals, with a reduction in viruses in the lung and a decrease in the degree of infection of this organ. These latest findings indicate that this approach can be used as a form of treatment.
Based on these findings, the proposal is to carry out the treatment in humans using a group of children who preferably ingest fiber through addition to their diet, to verify whether the same effects occur in both the most severe cases and moderate manifestations.
Patent
Marco Aurélio recalls that the results led the group to apply for a patent for the use of short-chain fatty acids and molecules that act through the same mechanism of action in the treatment of viral diseases and that the idea is to obtain partnerships to carry out tests on humans. He explains: “We showed that the increase in short-chain fatty acids in animals determines greater protection against the infection studied and we detected the mechanism involved. We identified a cellular protein that establishes the connection between short-chain fatty acids and their protective action, the GPR43 receptor, present in lung cells. What we patented was the use of short-chain fatty acids or similar molecules that activate this receptor, which in turn acts to combat viral infectious diseases.”
In summary, says the researcher, the use of a fiber diet protects animals against infection by the RSV virus. This protection is achieved with the generation of compounds by the intestinal microbiota, called short-chain fatty acids, which act in the lung by activating protective GPR43 receptors.
