Research indicates that SARS-CoV-2 – the virus that causes COVID – can directly attack the epithelial cells that line the gastrointestinal tract, entering through the angiotensin-2 converting enzyme molecular gate ( ACE2). These cells express high levels of ACE2, just like the cells that line the lungs, the main site of infection.
But the gut is not just a passive target for the virus. Evidence suggests that he is also a player in determining the severity of COVID-19. An explosion of research over the past decade has shown that the tiny inhabitants of the digestive tract – the gut microbiota – play a vital role in protecting the body from pathogens and in regulating immune responses to infections, and it seems. be the case for COVID. .
Billions of bacteria, fungi, viruses and other single-celled organisms reside in the gastrointestinal tract in a dynamic, commensal ecosystem. And each of us is home to our own unique community. When our gut microbiota is in a diverse but healthy and balanced state, it supports the proper functioning of our immune system. When the balance is disturbed – a condition scientists call dysbiosis – our defenses are compromised and we are more susceptible to infections.
We know that the diversity of the intestinal microbiota decreases with age. And similarly, there is an association between altered gut microbiota and chronic diseases, such as obesity, diabetes, and cardiovascular disease, conditions that predispose individuals to severe COVID-19. There is no evidence yet of a direct relationship between the severity of COVID and gut dysbiosis, but the evidence is mounting.
In a 2021 study of 100 hospital patients with COVID, Siew C. Ng and colleagues at the Chinese University of Hong Kong found that, overall, subjects’ gut microbiome (as measured in stool samples ) was significantly less diverse than samples taken from a prepandemic control group, regardless of whether patients were taking antibiotics or other medications. A number of advantages bacterial species were deficient in COVID patients, and the degree of microbiome disruption correlated with disease severity and increased signs of inflammation.
“Several intestinal microorganisms with known immunomodulatory function have been depleted in patients with COVID-19,” says Ng. Their depletion could be a factor in the “cytokine storm,” the dangerous hyperinflammatory state that is sometimes seen in COVID patients, says Ng, who is associate director of the Gut Microbiota Research Center at Chinese University of Hong Kong.
This scenario is one of the many ways our gut residents could influence the severity of COVID. The precise mechanisms are not yet known, “but we can make hypotheses,” says Harry Sokol, who studies the relationship between gut microbes and the immune system at Saint-Antoine Hospital in Paris. He suggests that “in the early phase of infection, there is an alteration of the intestinal microbiota leading to a decrease in the production of microbiota derivatives. [substances] which are important in controlling the infection. Such changes were seen in a 2021 study led by Sokol in which macaques were infected with SARS-CoV-2.
In a later phase of COVID, suggests Sokol, the decline of certain microbes could impact the integrity of the gut. These microbes normally generate substances that help maintain the intestinal lining, including short chain fatty acids such as butyric acid. Lower levels of key bacteria could therefore cause a “leaky gut,” which in turn could cause the leaching of pro-inflammatory molecules, thus increasing cytokine storms that can cause the significant organ damage seen in cases. severe COVID.
Damage to the intestine itself and to other organs can be the result of inflammation, the viral attack itself, or the disruption of normal ACE2 functions. In the intestine, ACE2 plays many roles, including regulating the ecology of the gut microbiota. So, it is not clear whether COVID causes an unhealthy gut or if an unhealthy gut sets the stage for severe COVID. “The two are probably true and related,” Sokol says.
Gut microbes can influence COVID results through an exchange of chemical signals with cells in the lungs. This recently discovered “gut-lung axis”, like most biological axes, is a two-way street: gut microbes influence how the lungs respond to infections, and lung inflammation can also alter the gut microbiota. For example, a synthesis study by Brazilian scientists published earlier this year found that research showed that chemical signals sent by gut bacteria and received by cells in the lungs can help protect mice from infection with an influenza virus, while giving mice antibiotics that disrupt their gut microbiota compromises their immune response to the flu virus. influenza. While the same is true for COVID in humans, clinicians should be careful about the use of antibiotics in COVID patients, unless, of course, they have secondary microbial infections.
As scientists learn more about the gut’s role in COVID, there may be other implications for treatment and prevention. Monitoring gut health can be a way to predict severity, and using probiotics and an improved diet to stimulate the microbiome could prove to be a valuable strategy. Ng notes that several randomized trials with a specially formulated blend of probiotics are underway at his facility: these trials aim to reduce the risk of COVID in vulnerable groups such as the elderly and people with diabetes and improve the response to COVID vaccines. Other researchers are also testing the possible benefits of using probiotics and transplanting fecal organisms in COVID patients with deficient gut populations.
There may even be lessons for the dreaded “long COVID”. In their 2021 study, Ng and his colleagues found that gut dysbiosis persisted in many recovered COVID patients when the virus was no longer detectable and could contribute to persistent health problems. The study followed some patients for 30 days after recovery, and the authors believe longer follow-up for this problem is warranted. It may be advised, Ng says, that “recovered patients consume diets or incorporate activities known to be good for the gut microbiome: increasing fiber intake, taking probiotics, and exercising.” This is good advice in all circumstances.
This article is part of an editorially independent Springer Nature collection which was carried out with the financial support of Lonza.