The Need for Healthy Microbes in the Era of COVID-19

New research shows nuance in the microbe conversation is key.

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Elena Mozhvilo/Unsplash

Over the last 10 years, health-related discussions have taken a major turn. Microbes, once largely portrayed as disease causing “germs,” were cast in a new light. Conversations about the importance of the gut microbiome filtered through mainstream news outlets. The idea of consuming bacteria for health (probiotics) became big business. Understanding how to preserve and augment the balance of bugs in the gut caused us to question excessive antibiotic use and reexamine the benefit of dietary fiber. In many ways, we learned that we actually needed more microbes in our life. Then came 2020.

Few health events rival the impact of the 2019 coronavirus (SARS-CoV-2) pandemic. In the span of only a few months, millions were infected. Entire countries were placed in lockdown for fear of viral transmission. Frequent washing of hands and profuse use of hand sanitizer went from helpful hygiene tips to public health imperatives. In contrast with the friendly microbes of the GI tract, the coronavirus became enemy №1. And while these tactics may be necessary for the foreseeable future, it’s important that we don’t lose sight of the role of our healthy microbes while we’re fighting off the coronavirus. Beyond improving basic health, preserving the wellbeing of our good bugs may even help us in the war against COVID-19.

When faced with uncertainty and danger, the human brain tends to revert to less nuanced thought. Grey is funneled into black and white buckets. In the case of COVID-19, there’s a real danger that our take on all microbes becomes tainted by one virus. At the extremes, this may contribute to mysophobia — a pathological generalized fear of germs. Yet for most of us, an increased negativity towards microbes may mean missing out on the benefits of healthy bugs. To understand our tendency to villianize microbes, and why we need to be cautious of it, we need to look into our past.

A few thousand years ago, contagiousness and effects of infectious diseases were attributed to evil spirits and gods. Greek texts later emphasized the role of geographic and meteorological influences on infectious disease. This concept informed the creation of “miasma theory,” the idea that air contaminated with poisonous vapors called “miasmas” caused disease. It wouldn’t be until 1862 that chemist Louis Pasteur would propose “germ theory” and solidify the link between microorganisms and disease.

Germ theory spread across the world in the subsequent centuries, leading to widespread use of techniques like water decontamination, antibiotics, pasteurization and sterilization of foods. But while the net effect is positive, there’s concern that hyperfocus on sterility and antimicrobials may have consequences. This is best exemplified by the hygiene hypothesis, which links our decreased exposure to microbes to an increased risk for autoimmune and allergic disease. Heavy antibiotic use has also led to fear of antibiotic resistance and for diseases associated with subsequent imbalances in our microbes.

In an ironic twist, our well-intentioned attempt to eradicate pathogens over the last century may have paved the way for worse COVID-19 outcomes. One reason for this comes back to the overuse of antibiotics, which is proposed to lead to lower microbial diversity. This microbial imbalance (called dysbiosis) is associated with multiple inflammatory conditions including heart disease, diabetes, obesity and COPD, which are among the top risk factors for severe COVID-19.

COVID-19 has also been more directly linked to our resident microbes. Compared with healthy controls, people with COVID-19 demonstrate significant alterations in their microbiome (the collection of bugs that live in and on us as well as their genetic components and metabolic products they produce), with a decrease in healthy gut bacteria and an increase in potentially harmful bugs. At a global scale, geographic alterations in the microbiome as a result of sanitation practices are proposed to play a role in COVID-19 outcomes. The basic idea: without adequate exposure to parasites and bacteria, our immune cells are thought to miss out on essential “training,” which makes us vulnerable to infections like COVID-19. So how do we actually link the immune system with the microbiome?

To maintain homeostasis, our bodies perform a delicate balancing act. We need to take in nutrients and information from the outside world without letting in dangerous pathogens and other antigens. But while barriers like our skin, lungs, and urogenital tracts are all part of this exchange, the gut is most central to this story. The gut, a 32 square meter tube running from mouth to anus, is populated by trillions of microbes. These bugs can alter immune function directly or by way of their metabolic byproducts. Conversely, the immune system helps shape the microbiome.

When communication between immune cells and microbes is balanced, health is preserved. Conversely, alterations in this interconnected web of data transfer may increase risk for metabolic, inflammatory and infectious diseases. For example, short chain fatty acids (SCFAs) are a metabolic byproduct of certain gut microbes. In addition to helping promote a strong gut barrier, SCFAs may help regulate the function of regulatory T cells (Tregs), an immune cell that helps quell excessive inflammation and is notably depleted in severe COVID-19. In order to produce SCFAs, microbes need the right fuel. This turns out to be primarily dietary fiber, a carbohydrate class largely depleted in the Western-style diet.

The immuno-regulatory role of the microbiome becomes more remarkable in the context of the severe immune dysregulation associated with COVID-19. In these cases, severe complications are associated with an overwhelming inflammatory response called the “cytokine storm.” This hyper-activation of the immune system is characterized by pronounced elevation in inflammatory immune molecules. Since the microbiome influences the reactivity of the immune thermostat, it’s possible that the health of the microbiome could influence a person’s propensity to experience the cytokine storm. The microbiome also work further upstream in the process. Evidence suggests that microbial factors help regulate the expression of the ACE2 receptor — a cell surface protein that SARS-CoV-2 uses to enter our cells. Most recently, it was revealed that the composition of the gut microbiome correlated with COVID disease severity and degree of the inflammatory immune response.

As we consider interventions to protect our health during the era of COVID-19 and in the future, the microbiome must be considered. So how do we support a healthier microbiome? In the most basic sense, we feed it what it needs. Prebiotic dietary fiber is a form of indigestible carbohydrate that acts as fuel for the gut microbiome. Examples of prebiotic fiber include inulin, acadia gum and psyllium. These can be found in foods like dandelion greens, garlic, onions, leeks and bananas.

Plant-derived molecules called polyphenols are also thought to have prebiotic properties. Polyphenols are found in higher concentrations in foods like green tea and coffee, but also exist in a wide range of vegetables and fruits. Some research additionally suggests that directly consuming healthy bacteria (probiotics) may positively influence health. Probiotics can be found in supplement form or in fermented foods. However, the precise impact of specific strains of probiotics in on health outcomes remains less clear. Finally, advocating for careful and conservative use of antibiotics whenever possible may help preserve the health of our resident bugs.

The COVID-19 pandemic assures that threat of infectious disease will majorly shape our thoughts and actions for the foreseeable future. Yet it’s important that we preserve the nuance within the story of human-microbe interactions. The last several decades have revealed that many of the microbes living on and in us may be neutral and even advantageous to our health, helping to offset risk for chronic disease and offering protection against other pathogenic microbes. While certain microbes including SARS-CoV-2 are overall damaging to our health, we should consider other microbes as integral in our defense against a variety of diseases, and support their wellbeing whenever possible.

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