A healthy microbiome builds a strong immune system that can help defeat COVID-19

Takeaways

• Your gut is home to trillions of bacteria that are essential to keep you healthy.

• Some of these microbes help regulate the immune system.

• New research, not yet evaluated by peers, shows that the presence of certain bacteria in the gut may reveal which people are more vulnerable to a more serious case of COVID-19.

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You may not know it, but there is an army of microbes in you that are essential for combating threats, including the virus that causes COVID-19.

In the last two decades, scientists have learned that our bodies are home to more bacterial cells than humans. This community of bacteria that lives in and on us – called the microbiome – seems like a business, with every micro-species doing specialized work, but all working to keep us healthy. In the gut, the bacteria balance the immune response against pathogens. These bacteria ensure that the immune response is effective, but not so violent that it collaterally damages the host.

Bacteria in our gut can elicit an effective immune response against viruses that not only infect the gut, such as norovirus and rotavirus, but also those that infect the lungs, such as the flu virus. The beneficial intestinal microbes do this by ordering specialized immune cells to produce powerful antiviral proteins that eventually eliminate viral infections. And the body of a person who does not have these beneficial gut bacteria does not have such an immune response to invasive viruses. As a result, infections can not be controlled, which can be detrimental to the health of the patient.

I am a microbiologist who is fascinated by the way bacteria shape human health. An important focus of my research is to determine how the beneficial bacteria that populate our gut fight diseases and infections. My most recent work focuses on the link between a particular microbe and the severity of COVID-19 in patients. My ultimate goal is to find out how I can improve the gut microbiome with diet to elicit a strong immune response – not only for SARS-CoV-2, but also for all pathogens.

How do you keep bacteria healthy?

Our immune system is part of a complex biological response against harmful pathogens, such as viruses or bacteria. Because our bodies are inhabited by trillions of mostly beneficial bacteria, viruses and fungi, our immune response is strictly regulated to distinguish between harmful and beneficial microbes.

Our bacteria are spectacular companions who zealously help protect our immune system to fight infections. A seminal study found that mice treated with antibiotics that eliminate bacteria in the gut showed a reduced immune response. These animals have low white blood cell counts that fight viruses, poor antibody responses and poor production of a protein that is essential for fighting viral infections and modulating the immune response.

In another study, mice were fed Lactobacillus bacteria, commonly used as probiotics in fermented foods. These microbes have reduced the severity of flu infection. The Lactobacillustreated mice did not lose weight and had only mild lung damage compared to untreated mice. Similarly, others have found that treating mice with Lactobacillus protects against various types of influenza virus and human respiratory synthesis virus – the leading cause of viral bronchiolitis and pneumonia in children.

Chronic diseases and microbes

Patients with chronic diseases, including type 2 diabetes, obesity and cardiovascular disease, exhibit a hyperactive immune system that cannot recognize a harmless stimulus and is linked to an altered intestinal microbiome.

In these chronic diseases, the intestinal microbiome lacks bacteria that activate immune cells that block the reaction against harmless bacteria in our intestines. Such a change in the intestinal microbiome is also observed in cesarean-born infants, in individuals on a poor diet, and in the elderly.

In the US, 117 million individuals – about half of the adult population – suffer from type 2 diabetes, obesity, cardiovascular disease or a combination thereof. This indicates that half of American adults have a faulty microbiome host.

Research in my laboratory focuses on identifying gut bacteria that are critical to creating a balanced immune system, fighting life-threatening bacterial and viral infections while tolerating the beneficial bacteria in and on us.

Since diet affects the diversity of bacteria in the gut, my laboratory studies show how diet can be used as a treatment for chronic diseases. With different foods, people can shift their gut microbiome to one that enhances a healthy immune response.

A fraction of patients infected with SARS-CoV-2, the virus that causes COVID-19 disease, develop serious complications that require hospitalization in intensive care units. What did many of the patients have in common? Age and chronic diseases related to diet, such as obesity, type 2 diabetes and cardiovascular disease.

Blacks and Latinx people are excessively affected by obesity, type 2 diabetes and cardiovascular disease, all of which are associated with poor nutrition. It is therefore no coincidence that these groups suffered more deaths due to COVID-19. It is not only in the US but also in Britain.

Discover microbes that predict the severity of COVID-19

The COVID-19 pandemic inspired me to shift my research and investigate the role of the gut microbiome in the overly aggressive immune response against SARS-CoV-2 infection.

My colleagues and I hypothesized that critically ill SARS-CoV-2 patients with conditions such as obesity, type 2 diabetes, and cardiovascular disease exhibited an altered intestinal microbiome that exacerbated the acute respiratory distress syndrome.

Acute respiratory distress syndrome, a life-threatening lung injury, is thought to develop in SARS-CoV-2 patients due to a fatal overreaction of the immune response, called a cytokine storm, which is an uncontrolled flood of immune cells in the lungs cause. In these patients, their own uncontrolled inflammatory immune response, rather than the virus itself, causes the severe lung injury and multiorgan failures that lead to death.

Several studies described in one recent review have identified an altered intestinal microbiome in patients with COVID-19. However, identification of specific bacteria within the microbiome that may predict COVID-19 severity is lacking.

To address this question, my colleagues and I recruited COVID-19 patients admitted to the hospital with severe and moderate symptoms. We collected stool and saliva samples to determine if bacteria in the gut and oral microbiome could predict the severity of COVID-19. Identifying microbiome markers that can predict the clinical outcomes of COVID-19 disease is key to prioritizing patients in need of urgent treatment.

In an article that has not yet been evaluated by the peer, we showed that the composition of the intestinal microbiome is the strongest predictor of COVID-19 severity compared to the clinical features that the patient usually uses. We specifically identified that the presence of a bacterium in the feces is mentioned Enterococcus faecalis– was a strong predictor of COVID-19 severity. Not surprisingly, Enterococcus faecalis is associated with chronic inflammation.

Enterococcus faecalis collected by feces can be grown in the clinical laboratories outside the body. So, a E. faecalis testing is a cost-effective, rapid, and relatively easy way to identify patients who are likely to need more supportive care and therapeutic interventions to improve their chances of survival.

However, it is not yet clear from our research what is the contribution of the altered microbiome in the immune response to SARS-CoV-2 infection. A recent study showed that SARS-CoV-2 infection causes an imbalance in immune cells called T-regulatory cells that are critical for immune balance.

Bacteria from the gut microbiome are responsible for the proper activation of those T-regulatory cells. Thus, researchers like me need to take repeated bowel movements, saliva and blood samples over a longer period of time to learn how the altered microbiome observed in COVID-19 patients can modulate the severity of COVID-19, perhaps through the development of the T-regulating cell.

As a Latina scientist researching interactions between diet, microbiome, and immunity, I must emphasize the importance of better policies to improve access to healthy foods, leading to a healthier microbiome. It is also important to design culture-sensitive dietary interventions for Black and Latinx communities. Although a good quality diet can not prevent SARS-CoV-2 infection, it can treat the underlying conditions associated with its severity.

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