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Molecules derived from microbiota do not alter the entry or replication of SARS-CoV-2 in intestinal cells

Publicado em 31 março 2021

A study conducted at the University of Campinas (UNICAMP) in São Paulo, Brazil, shows that compounds formed by the intestinal microbiota (bacteria and other microorganisms) during the fermentation of insoluble fiber from plant nutrients are not affected. -2 for penetration and replication in cells lining the intestine. However, while treatment of cells with these molecules in vitro had no significant effect on local tissue infection, it reduced the expression of a gene that plays a key role in the entry of viral cells, and a cytokine receptor that promotes inflammation.

An article reporting these results was published in the journal Intestine microbes.

Up to 50% of patients with COVID-1

9 experience gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. Such symptoms occur in 17.6% of severe cases. They are partly related to the penetration of viruses into intestinal cells, leading to a change in their normal functions. In addition, recent studies indicate serious changes in patients ’gut microbiota, including a decrease in the levels of bacteria that secrete short-chain fatty acids (GFAs) through the fermentation of dietary fiber. SCFAs are important for colon health and maintaining the integrity of the intestinal barrier.

The researchers decided to confirm whether SFCA affects intestinal SARS-CoV-2 cell infection. Previous studies have suggested changes in the gut microbiota and the foods contained in it can alter the immune response of an infected person.

“In earlier studies, we found in animals that compounds formed by the gut microbiota help protect the body from respiratory infection. The model used there had a respiratory syncytial virus[[[[RSV]causing bronchiolitis[[[[inflammation of the small airways in the lungs]and often infects children. Similar results have been obtained by other research groups in the study of various respiratory diseases, “said Patricia Brita Rodriguez, who has a doctorate from FAPESP and is the first author of an article with Libyan doctoral student Bitencourt Pascal. Rodriguez conducted research at the Institute of Science in Ph.D. (IB) UNICAMP with FAPESP Scholarship.

In a recent study, healthy colon tissue and epithelial cells were infected with SARS-CoV-2 in the laboratory and tested.

“Viral load was not reduced and was the same in SCFA-treated cells and tissues and in untreated samples. However, treated intestinal biopsy specimens showed a significant reduction in gene expression DDX58 [[[[an innate immune system receptor that detects viral nucleic acids and activates a signaling cascade that leads to the production of inflammatory cytokines]and the interferon-lambda receptor, which mediates antiviral activity. There is also a decrease in the expression of TMPRSS2 protein, which is very important for the entry of viral cells, “said Raquel Franco Leal, a professor at the UNICAMP School of Medicine (FCM), supported by FAPESP and the study’s interlocutor. FAPESP.

Protection against inflammation

The researchers took colon tissue samples from 11 patients without COVID-19. They also tested epithelial cells that line the intestines and are in close contact with the intestinal microbiota. Tissue and cell samples were infected with SARS-CoV-2 at the New Virus Research Laboratory (LEVE) of IB-UNICAMP, a Level III Biosafety Institution (BSL-3) headed by Jose Luis Praens Modena, Professor IB-UNICAMP and co-author of the article.

Tissues and cells were treated with a mixture of acetate, propionate and butyrate, compounds formed during the metabolism of intestinal microbiota SCFA present in dietary fiber. Treatment did not alter the viral load on biopsy or colon cells, nor did any changes in cell wall permeability and integrity occur.

"This does not rule out the possibility of a significant effect of SCFA on SARS-CoV-2 infection. Antiviral effects may depend on interactions with other cells in the body. We will continue to study in animal models, as the effect of these compounds on infection may depend on a more complete system than the samples we used in vitro.[[isolated cells and tissues]. “

Patricia Brita Rodriguez, first author

Other tests involving untreated biopsy specimens have shown increased gene expression DDX58, which encodes an important viral receptor, and interferon-beta (IFN-beta), a right-wing inflammatory molecule involved in cytokine storms associated with severe cases of COVID-19.

“Gene changes related to virus recognition and response during intestinal infection may be important for the onset of the inflammatory chain,” Leal said. “In this context, it will be important to deepen the analysis of the impact of SCFA with these parameters, as this can be significant in severe stages of the disease.”

Source:

Sao Paulo Research Foundation (FAPESP)

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Pascal, LB, et al. (2021) Short fatty acid chains derived from microbiota do not prevent SARS-CoV-2 infection by human colon samples. Intestine microbes. doi.org/10.1080/19490976.2021.1874740.

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