The data was published in the journal Gut Microbes
A study conducted at the State University of Campinas (Unicamp) demonstrates that compounds produced by the intestinal microbiota from the breakdown of dietary fiber do not interfere with the entry or replication of the SARS-CoV-2 virus in the intestine. But, although the treatment of cells in vitro with these molecules was not relevant to local tissue infection, it reduced the expression of an important gene for viral entry into cells and of a cytokine receptor that favors inflammation. The data was published in the journal Gut Microbes.
Gastrointestinal symptoms such as diarrhea, vomiting and abdominal pain can affect up to 50% of COVID-19 patients and 17,6% of severe cases. These changes are partly associated with the entry of the virus into intestinal cells and changes in their normal functions. Furthermore, recent studies indicate that individuals affected by the disease present important changes in the intestinal microbiota, including a reduction in bacteria that produce short-chain fatty acids – molecules that regulate intestinal cells and the body's defense.
Because of this, the researchers tested whether this type of fatty acid would have a direct effect on the infection of intestinal cells by SARS-CoV-2. Other studies have already indicated that changes in the intestinal microbiota and its products could modify the immune response during an infectious condition.
“In previous work, we observed in animals that compounds produced by the intestinal microbiota participate in protection against respiratory infection. In that case, we used respiratory syncytial virus [RSV], which causes bronchiolitis and is quite common in children, as a model. Similar results were obtained in studies conducted by other research groups, with different respiratory diseases”, explains doctoral fellow Patrícia Brito Rodrigues, who shares first authorship of the article with post-doctoral fellow Livia Bitencourt Pascoal. Rodrigues carried out the research as part of his doctorate at the Biology Institute (IB) at Unicamp, with a scholarship from FAPESP (read more at: agencia.fapesp.br/31539).
In the most recent work, healthy samples of tissue from the intestinal colon and epithelial cells from the same region were infected with the new coronavirus in the laboratory and then analyzed.
“There was no decrease in the amount of virus, which was the same both in cells and tissues treated with short-chain fatty acids and in samples that did not receive the treatment. However, the treated intestinal biopsy samples showed a significant drop in the expression of the DDX58 gene [a receptor of the innate immune system that detects viral nucleic acids and activates a signaling cascade that results in the production of pro-inflammatory cytokines] and the interferon receptor. lambda, which mediates antiviral activity. The TMPRSS2 protein, which is important for the entry of the virus into cells, also became less expressed”, says Raquel Franco Leal, professor at the Faculty of Medical Sciences (FCM) at Unicamp supported by FAPESP and coordinator of the study together with Marco Aurélio Ramirez Vinolo, professor at the IB-Unicamp also supported by the Foundation.
Protection against inflammation
The researchers collected colon tissue samples from 11 patients without COVID-19. The tests were also carried out on intestinal epithelial cells, which form the most superficial part of the intestine and are in close contact with the intestinal microbiota. Both tissue samples and cells were infected with SARS-CoV-2 at the Emerging Virus Studies Laboratory (Leve), which has biosafety level 3 (NB3) and is coordinated by José Luiz Proença Módena, professor at IB- Unicamp and co-author of the article.
The tissues and cells were treated with a mixture of acetate, propionate and butyrate, compounds obtained in the intestine through the metabolization, by the intestinal microbiota, of short-chain fatty acids present in dietary fiber. The treatment did not change the viral load of intestinal biopsies or cells. There were also no changes in the permeability and integrity of the cell walls.
“This does not exclude the possibility that short-chain fatty acids have a significant action in SARS-CoV-2 infection. Perhaps the antiviral effects depend on interactions with other cells in the body. We will continue investigating, now in animal models, as it is possible that the action of these compounds in infection depends on a more complete system than those we use [isolated cells and tissues] in vitro”, says Rodrigues.
Other tests showed, in untreated infected biopsies, increased expression of the DDX58 gene, which encodes an important viral receptor. Furthermore, there was also greater expression of interferon-beta (IFN-beta), a pro-inflammatory molecule that participates in the phenomenon known as cytokine storm, associated with the most severe cases of COVID-19.
“Changes in virus recognition and response genes during intestinal infection may be relevant to the initiation of the inflammatory chain. In this context, it will be important to further analyze the effects of short-chain fatty acids under these parameters, as this may be important in the most severe phase of the disease”, adds Leal.
The article Microbiota-derived short-chain fatty acids do not interfere with SARS-CoV-2 infection of human colonic samples can be read at: www.tandfonline.com/doi/full/10.1080/19490976.2021.1874740.
original article published on the Agência Fapesp website.
