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A Wholesome Microbiome Builds a Sturdy Immune System That Might Assist Defeat Covid-19

By Ana Maldonado-Contreras, University of Massachusetts Medical School

Takeaways

  • Trillions of bacteria live in your gut and are vital to your health.
  • Some of these microbes help regulate the immune system.
  • New research, which has not yet been peer-reviewed, shows that the presence of certain bacteria in the gut may shed some light on which people are more prone to a more severe case of COVID-19.

You may not know, but you have an army of microbes living inside you that are essential to warding off threats, including the virus that causes COVID-19.

Over the past two decades, scientists have learned that there are more bacterial cells in our bodies than in human cells. This community of bacteria that lives in and on us – the so-called microbiome – is similar to a company in which each type of microbe performs specific tasks, but everyone works to keep us healthy. In the intestine, the bacteria balance the immune response against pathogens. These bacteria ensure that the immune response is effective but not so violent that it causes collateral damage to the host.

Bacteria in our gut can create 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 gut microbes do this by commanding specialized immune cells to produce potent antiviral proteins that ultimately eliminate viral infections. And a person’s body lacking these beneficial gut bacteria doesn’t have as strong an immune response to invading viruses. As a result, infections can go uncontrolled and affect health.

I am a microbiologist who is intrigued by the way bacteria shape human health. A major focus of my research is to find out how the beneficial bacteria that populate our intestines fight diseases and infections. My recent work focuses on the relationship between a specific microbe and the severity of COVID-19 in patients. My ultimate goal is to find out how the gut microbiome can be improved through diet in order to generate a strong immune response – not just for SARS-CoV-2, but for all pathogens.

How do resident bacteria keep you healthy?

Our immune system is part of a complex biological reaction against harmful pathogens such as viruses or bacteria. However, since our body is inhabited by billions of mostly beneficial bacteria, viruses and fungi, the activation of our immune response is strictly regulated to distinguish between harmful and helpful microbes.

Our bacteria are spectacular companions that diligently help to strengthen the defenses of our immune system in order to fight infections. One landmark study found that mice treated with antibiotics that eliminate bacteria in the gut exhibited an impaired immune response. These animals had low virus-fighting white blood cell counts, weak antibody responses, and poor production of a protein that is critical to fighting viral infection and modulating the immune response.

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

Chronic diseases and microbes

Patients with chronic diseases such as type 2 diabetes, obesity, and cardiovascular disease have a hyperactive immune system that does not recognize a harmless stimulus and is associated with an altered gut microbiome.

In these chronic diseases, the gut microbiome lacks bacteria that activate immune cells that block the reaction against harmless bacteria in our intestines. Such a change in the gut microbiome is also seen in babies born by a caesarean section, those who eat poorly, and the elderly.

In the United States, 117 million people – about half the adult population – have type 2 diabetes, obesity, cardiovascular disease, or a combination of these. This suggests that half of American adults carry a faulty microbiome army.

The research in my lab focuses on identifying gut bacteria that are vital to creating a balanced immune system that fights life-threatening bacterial and viral infections while tolerating the beneficial bacteria in and on us.

Given that diet affects the diversity of bacteria in the gut, my laboratory studies show how diet can be used as therapy for chronic diseases. By using different foods, people can shift their gut microbiome to one that promotes a healthy immune response.

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

Black and Latinx people are disproportionately affected by obesity, type 2 diabetes, and cardiovascular disease, all of which are linked to poor diet. Therefore, it is no coincidence that these groups have suffered more deaths from COVID-19 compared to whites. This is the case not only in the US but also in the UK.

Discovery of microbes that predict the severity of COVID-19

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

My colleagues and I have hypothesized that critically ill SARS-CoV-2 patients with conditions such as obesity, type 2 diabetes, and cardiovascular disease have an altered gut microbiome that makes acute respiratory distress syndrome worse.

Acute respiratory distress syndrome, a life-threatening lung injury, is believed to develop in SARS-CoV-2 patients from a fatal overreaction of the immune response known as a cytokine storm, which causes an uncontrolled flood of immune cells into the lungs. In these patients, instead of the virus itself, it is their own uncontrolled inflammatory immune response that causes the severe lung injury and multiple organ failure that lead to death.

Several studies described in a recent review have identified an altered gut microbiome in patients with COVID-19. However, there is a lack of identification of specific bacteria within the microbiome that could predict the severity of COVID-19.

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

In an article that has not yet been peer-reviewed, we showed that the composition of the gut microbiome is the strongest predictor of the severity of COVID-19 compared to the patient’s commonly used clinical characteristics. In particular, we found that the presence of a bacterium in stool – called Enterococcus faecalis – was a robust predictor of the severity of COVID-19. Not surprisingly, Enterococcus faecalis has been linked to chronic inflammation.

Enterococcus faecalis obtained from feces can be grown outside the body in clinical laboratories. An E. faecalis test could therefore be an inexpensive, quick, and relatively simple way to identify patients who are likely to require more support and therapeutic intervention to improve their chances of survival.

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

Bacteria from the gut microbiome are responsible for the proper activation of these T-regulatory cells. Therefore, researchers like me need to repeatedly collect stool, saliva, and blood samples from patients over an extended period of time to learn how the altered microbiome observed in COVID-19 patients can modulate the severity of COVID-19 disease, possibly through change the development of T-regulatory cells.

As a Latina scientist studying the interactions between diet, microbiome, and immunity, I must highlight the importance of better strategies to improve access to healthy foods that result in a healthier microbiome. It is also important to develop culturally sensitive nutritional interventions for black and Latin American communities. While a good quality diet may not prevent SARS-CoV-2 infection, it can treat the underlying conditions associated with its severity.

[Get our best science, health and technology stories. Sign up for The Conversation’s science newsletter.]The conversation

Ana Maldonado-Contreras, Assistant Professor of Microbiology and Physiological Systems, University of Massachusetts Medical School

This article is republished by The Conversation under a Creative Commons license. Read the original article.

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