A Healthy Microbiome Builds a Strong Immune System That Could Help Defeat COVID-19
By Ana Maldonado-Contreras
- Your gut is home to trillions of bacteria that are vital for keeping you healthy.
- Some of these microbes help to regulate the immune system.
- New research, which has not yet been peer-reviewed, shows the presence of certain bacteria in the gut may reveal which people are more vulnerable to a more severe case of COVID-19.
You may not know it, but you have an army of microbes living inside of you that are essential for fighting off threats, including the virus that causes COVID-19.
In the past two decades scientists have learned our bodies are home to more bacterial cells than human ones. This community of bacteria that lives in and on us – called the microbiome – resembles a company, with each microbe species performing specialized jobs but all working to keep us healthy. In the gut, the bacteria balance the immune response against pathogens. These bacteria ensure the immune response is effective but not so violent that it causes collateral damage to the host.
Bacteria in our guts can elicit an effective immune response against viruses that not only infect the gut, such as norovirus and rotavirus, but also those infecting the lungs, such as the flu virus. The beneficial gut microbes do this by ordering specialized immune cells to produce potent antiviral proteins that ultimately eliminate viral infections. And the body of a person lacking these beneficial gut bacteria won't have as strong an immune response to invading viruses. As a result, infections might go unchecked, taking a toll on health.
I am a microbiologist fascinated by the ways bacteria shape human health. An important focus of my research is figuring out how the beneficial bacteria populating our guts combat disease and infection. 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 figure out out how to enhance the gut microbiome with diet to evoke a strong immune response – for not just SARS-CoV-2 but all pathogens.
How Do Resident Bacteria Keep You Healthy?
Our immune defense is part of a complex biological response against harmful pathogens, such as viruses or bacteria. However, because our bodies are inhabited by trillions of mostly beneficial bacteria, virus and fungi, activation of our immune response is tightly regulated to distinguish between harmful and helpful microbes.
Our bacteria are spectacular companions diligently helping prime our immune system defenses to combat infections. A seminal study found that mice treated with antibiotics that eliminate bacteria in the gut exhibited an impaired immune response. These animals had low counts of virus-fighting white blood cells, weak antibody responses and poor production of a protein that is vital for combating viral infection and modulating the immune response.
In another study, mice were fed Lactobacillus bacteria, commonly used as probiotic in fermented food. These microbes reduced the severity of influenza infection. The Lactobacillus-treated mice did not lose weight and had only mild lung damage compared with untreated mice. Similarly, others have found that treatment of mice with Lactobacillus protects against different subtypes of influenza virus and human respiratory syncytial virus – the major cause of viral bronchiolitis and pneumonia in children.
Chronic Disease and Microbes
Patients with chronic illnesses including Type 2 diabetes, obesity and cardiovascular disease exhibit a hyperactive immune system that fails to recognize a harmless stimulus and is linked to an altered gut microbiome.
In these chronic diseases, the gut microbiome lacks bacteria that activate immune cells that block the response against harmless bacteria in our guts. Such alteration of the gut microbiome is also observed in babies delivered by cesarean section, individuals consuming a poor diet and the elderly.
In the U.S., 117 million individuals – about half the adult population – suffer from Type 2 diabetes, obesity, cardiovascular disease or a combination of them. That suggests that half of American adults carry a faulty microbiome army.
Research in my laboratory focuses on identifying gut bacteria that are critical for creating a balanced immune system, which 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 lab studies show how diet can be used as a therapy for chronic diseases. Using different foods, people can shift their gut microbiome to one that boosts a healthy immune response.
A fraction of 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 those patients have in common? Old age and chronic diet-related diseases like 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 nutrition. Thus, it is not a coincidence that these groups have suffered more deaths from COVID-19 compared with whites. This is the case not only in the U.S. but also in Britain.
Discovering Microbes That Predict COVID-19 Severity
The COVID-19 pandemic has inspired me to shift my research and explore the role of the gut microbiome in the overly aggressive immune response against SARS-CoV-2 infection.
My colleagues and I have hypothesized that critically ill SARS-CoV-2 patients with conditions like obesity, Type 2 diabetes and cardiovascular disease exhibit an altered gut microbiome that aggravates acute respiratory distress syndrome.
Acute respiratory distress syndrome, a life-threatening lung injury, in SARS-CoV-2 patients is thought to develop from a fatal overreaction of the immune response called a cytokine storm that causes an uncontrolled flood of immune cells into the lungs. 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 gut microbiome in patients with COVID-19. However, identification of specific bacteria within the microbiome that could predict COVID-19 severity is lacking.
To address this question, my colleagues and I recruited COVID-19 hospitalized patients with severe and moderate symptoms. We collected stool and saliva samples to determine whether bacteria within the gut and oral microbiome could predict COVID-19 severity. The identification of microbiome markers that can predict the clinical outcomes of COVID-19 disease is key to help prioritize patients needing urgent treatment.
We demonstrated, in a paper which has not yet been peer reviewed, that the composition of the gut microbiome is the strongest predictor of COVID-19 severity compared to patient's clinical characteristics commonly used to do so. Specifically, we identified that the presence of a bacterium in the stool – called Enterococcus faecalis– was a robust predictor of COVID-19 severity. Not surprisingly, Enterococcus faecalis has been associated with chronic inflammation.
Enterococcus faecalis collected from feces can be grown outside of the body in clinical laboratories. Thus, an E. faecalis test might be a cost-effective, rapid and relatively easy way to identify patients who are likely to require more supportive care and therapeutic interventions to improve their chances of survival.
But 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 has shown that SARS-CoV-2 infection triggers an imbalance in immune cells called T regulatory cells that are critical to 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 patient stool, saliva and blood samples over a longer time frame to learn how the altered microbiome observed in COVID-19 patients can modulate COVID-19 disease severity, perhaps by altering the development of the T-regulatory cells.
As a Latina scientist investigating interactions between diet, microbiome and immunity, I must stress the importance of better policies to improve access to healthy foods, which lead to a healthier microbiome. It is also important to design culturally sensitive dietary interventions for Black and Latinx communities. While a good-quality diet might not prevent SARS-CoV-2 infection, it can treat the underlying conditions related to its severity.
Ana Maldonado-Contreras is an assistant professor of Microbiology and Physiological Systems at the University of Massachusetts Medical School.
Disclosure statement: Ana Maldonado-Contreras receives funding from The Helmsley Charitable Trust and her work has been supported by the American Gastroenterological Association. She received The Charles A. King Trust Postdoctoral Research Fellowship. She is also member of the Diversity Committee of the American Gastroenterological Association.
Reposted with permission from The Conversation.
By Dana M Bergstrom, Euan Ritchie, Lesley Hughes and Michael Depledge
In 1992, 1,700 scientists warned that human beings and the natural world were "on a collision course." Seventeen years later, scientists described planetary boundaries within which humans and other life could have a "safe space to operate." These are environmental thresholds, such as the amount of carbon dioxide in the atmosphere and changes in land use.
The Good and Bad News<p><span>Ecosystems consist of living and non-living components, and their interactions. They work like a super-complex engine: when some components are removed or stop working, knock-on consequences can lead to system failure.</span></p><p>Our study is based on measured data and observations, not modeling or predictions for the future. Encouragingly, not all ecosystems we examined have collapsed across their entire range. We still have, for instance, some intact reefs on the Great Barrier Reef, especially in deeper waters. And northern Australia has some of the most intact and least-modified stretches of savanna woodlands on Earth.</p><p><span>Still, collapses are happening, including in regions critical for growing food. This includes the </span><a href="https://www.mdba.gov.au/importance-murray-darling-basin/where-basin" target="_blank" rel="noopener noreferrer">Murray-Darling Basin</a><span>, which covers around 14% of Australia's landmass. Its rivers and other freshwater systems support more than </span><a href="https://www.abs.gov.au/ausstats/[email protected]/latestproducts/94F2007584736094CA2574A50014B1B6?opendocument" target="_blank" rel="noopener noreferrer">30% of Australia's food</a><span> production.</span></p><p><span></span><span>The effects of floods, fires, heatwaves and storms do not stop at farm gates; they're felt equally in agricultural areas and natural ecosystems. We shouldn't forget how towns ran out of </span><a href="https://www.mdba.gov.au/issues-murray-darling-basin/drought#effects" target="_blank" rel="noopener noreferrer">drinking water</a><span> during the recent drought.</span></p><p><span></span><span>Drinking water is also at risk when ecosystems collapse in our water catchments. In Victoria, for example, the degradation of giant </span><a href="https://theconversation.com/logging-must-stop-in-melbournes-biggest-water-supply-catchment-106922" target="_blank" rel="noopener noreferrer">Mountain Ash forests</a><span> greatly reduces the amount of water flowing through the Thompson catchment, threatening nearly five million people's drinking water in Melbourne.</span></p><p>This is a dire <em data-redactor-tag="em">wake-up</em> call — not just a <em data-redactor-tag="em">warning</em>. Put bluntly, current changes across the continent, and their potential outcomes, pose an existential threat to our survival, and other life we share environments with.</p><p><span>In investigating patterns of collapse, we found most ecosystems experience multiple, concurrent pressures from both global climate change and regional human impacts (such as land clearing). Pressures are often </span><a href="https://besjournals.onlinelibrary.wiley.com/doi/abs/10.1111/1365-2664.13427" target="_blank" rel="noopener noreferrer">additive and extreme</a><span>.</span></p><p>Take the last 11 years in Western Australia as an example.</p><p>In the summer of 2010 and 2011, a <a href="https://theconversation.com/marine-heatwaves-are-getting-hotter-lasting-longer-and-doing-more-damage-95637" target="_blank" rel="noopener noreferrer">heatwave</a> spanning more than 300,000 square kilometers ravaged both marine and land ecosystems. The extreme heat devastated forests and woodlands, kelp forests, seagrass meadows and coral reefs. This catastrophe was followed by two cyclones.</p><p>A record-breaking, marine heatwave in late 2019 dealt a further blow. And another marine heatwave is predicted for <a href="https://www.theguardian.com/environment/2020/dec/24/wa-coastline-facing-marine-heatwave-in-early-2021-csiro-predicts" target="_blank" rel="noopener noreferrer">this April</a>.</p>
What to Do About It?<p><span>Our brains trust comprises 38 experts from 21 universities, CSIRO and the federal Department of Agriculture Water and Environment. Beyond quantifying and reporting more doom and gloom, we asked the question: what can be done?</span></p><p>We devised a simple but tractable scheme called the 3As:</p><ul><li>Awareness of what is important</li><li>Anticipation of what is coming down the line</li><li>Action to stop the pressures or deal with impacts.</li></ul><p>In our paper, we identify positive actions to help protect or restore ecosystems. Many are already happening. In some cases, ecosystems might be better left to recover by themselves, such as coral after a cyclone.</p><p>In other cases, active human intervention will be required – for example, placing artificial nesting boxes for Carnaby's black cockatoos in areas where old trees have been <a href="https://www.environment.gov.au/biodiversity/threatened/publications/factsheet-carnabys-black-cockatoo-calyptorhynchus-latirostris" target="_blank" rel="noopener noreferrer">removed</a>.</p><p><span>"Future-ready" actions are also vital. This includes reinstating </span><a href="https://www.abc.net.au/gardening/factsheets/a-burning-question-fire/12395700" target="_blank" rel="noopener noreferrer">cultural burning practices</a><span>, which have </span><a href="https://theconversation.com/australia-you-have-unfinished-business-its-time-to-let-our-fire-people-care-for-this-land-135196" target="_blank" rel="noopener noreferrer">multiple values and benefits for Aboriginal communities</a><span> and can help minimize the risk and strength of bushfires.</span></p><p>It might also include replanting banks along the Murray River with species better suited to <a href="https://www.abc.net.au/gardening/factsheets/my-garden-path---matt-hansen/12322978" target="_blank" rel="noopener noreferrer">warmer conditions</a>.</p><p>Some actions may be small and localized, but have substantial positive benefits.</p><p>For example, billions of migrating Bogong moths, the main summer food for critically endangered mountain pygmy possums, have not arrived in their typical numbers in Australian alpine regions in recent years. This was further exacerbated by the <a href="https://theconversation.com/six-million-hectares-of-threatened-species-habitat-up-in-smoke-129438" target="_blank" rel="noopener noreferrer">2019-20</a> fires. Brilliantly, <a href="https://www.zoo.org.au/" target="_blank" rel="noopener noreferrer">Zoos Victoria</a> anticipated this pressure and developed supplementary food — <a href="https://theconversation.com/looks-like-an-anzac-biscuit-tastes-like-a-protein-bar-bogong-bikkies-help-mountain-pygmy-possums-after-fire-131045" target="_blank" rel="noopener noreferrer">Bogong bikkies</a>.</p><p><span>Other more challenging, global or large-scale actions must address the </span><a href="https://www.youtube.com/watch?v=iICpI9H0GkU&t=34s" target="_blank" rel="noopener noreferrer">root cause of environmental threats</a><span>, such as </span><a href="https://www.nature.com/articles/s41559-018-0504-8" target="_blank" rel="noopener noreferrer">human population growth and per-capita consumption</a><span> of environmental resources.</span><br></p><p>We must rapidly reduce greenhouse gas emissions to net-zero, remove or suppress invasive species such as <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/mam.12080" target="_blank" rel="noopener noreferrer">feral cats</a> and <a href="https://theconversation.com/the-buffel-kerfuffle-how-one-species-quietly-destroys-native-wildlife-and-cultural-sites-in-arid-australia-149456" target="_blank" rel="noopener noreferrer">buffel grass</a>, and stop widespread <a href="https://theconversation.com/to-reduce-fire-risk-and-meet-climate-targets-over-300-scientists-call-for-stronger-land-clearing-laws-113172" target="_blank" rel="noopener noreferrer">land clearing</a> and other forms of habitat destruction.</p>
Our Lives Depend On It<p>The multiple ecosystem collapses we have documented in Australia are a harbinger for <a href="https://www.iucn.org/news/protected-areas/202102/natures-future-our-future-world-speaks" target="_blank">environments globally</a>.</p><p>The simplicity of the 3As is to show people <em>can</em> do something positive, either at the local level of a landcare group, or at the level of government departments and conservation agencies.</p><p>Our lives and those of our <a href="https://theconversation.com/children-are-our-future-and-the-planets-heres-how-you-can-teach-them-to-take-care-of-it-113759" target="_blank">children</a>, as well as our <a href="https://theconversation.com/taking-care-of-business-the-private-sector-is-waking-up-to-natures-value-153786" target="_blank" rel="noopener noreferrer">economies</a>, societies and <a href="https://theconversation.com/to-address-the-ecological-crisis-aboriginal-peoples-must-be-restored-as-custodians-of-country-108594" target="_blank" rel="noopener noreferrer">cultures</a>, depend on it.</p><p>We simply cannot afford any further delay.</p><p><em><a rel="noopener noreferrer" href="https://theconversation.com/profiles/dana-m-bergstrom-1008495" target="_blank" style="">Dana M Bergstrom</a> is a principal research scientist at the University of Wollongong. <a rel="noopener noreferrer" href="https://theconversation.com/profiles/euan-ritchie-735" target="_blank" style="">Euan Ritchie</a> is a professor in Wildlife Ecology and Conservation, Centre for Integrative Ecology, School of Life & Environmental Sciences at Deakin University. <a rel="noopener noreferrer" href="https://theconversation.com/profiles/lesley-hughes-5823" target="_blank">Lesley Hughes</a> is a professor at the Department of Biological Sciences at Macquarie University. <a rel="noopener noreferrer" href="https://theconversation.com/profiles/michael-depledge-114659" target="_blank">Michael Depledge</a> is a professor and chair, Environment and Human Health, at the University of Exeter. </em></p><p><em>Disclosure statements: Dana Bergstrom works for the Australian Antarctic Division and is a Visiting Fellow at the University of Wollongong. Her research including fieldwork on Macquarie Island and in Antarctica was supported by the Australian Antarctic Division.</em></p><p><em>Euan Ritchie receives funding from the Australian Research Council, The Australia and Pacific Science Foundation, Australian Geographic, Parks Victoria, Department of Environment, Land, Water and Planning, and the Bushfire and Natural Hazards CRC. Euan Ritchie is a Director (Media Working Group) of the Ecological Society of Australia, and a member of the Australian Mammal Society.</em></p><p><em>Lesley Hughes receives funding from the Australian Research Council. She is a Councillor with the Climate Council of Australia, a member of the Wentworth Group of Concerned Scientists and a Director of WWF-Australia.</em></p><p><em>Michael Depledge does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</em></p><p><em>Reposted with permission from <a href="https://theconversation.com/existential-threat-to-our-survival-see-the-19-australian-ecosystems-already-collapsing-154077" target="_blank" style="">The Conversation</a>. </em></p>
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