It’s a mystery that has puzzled the world’s virologists.
The United States and Western Europe — home to many of the planet’s best doctors and hospitals and the most robust public health infrastructures — have been among the regions hit hardest by the novel coronavirus.
Some have speculated that climate, population demographics, government response (or lack thereof), and other factors can explain the high numbers of infections in the developed world. And there is probably some truth to each of these hypotheses. But none seems to fully explain why half of the countries that make the top 10 in Covid-19 deaths per capita — a top 10 that includes the United States — are also among the wealthiest and most medically advanced in the world.
Heenam Stanley Kim, PhD, is a professor and microbial geneticist at Korea University in Seoul. He has his own hypothesis — one that has to do with the bacteria that live in the human gut. “Evidence accumulated around the world [suggests] that people who have an altered gut microbiota have a higher risk for serious Covid-19,” he says.
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The human gastrointestinal tract is home to trillions of bacteria, often collectively referred to as the gut microbiota or microbiome. The types, numbers, diversity, and proportions of these bacteria vary from person to person. While some species reliably populate the guts of healthy people and are therefore regarded as “good” or helpful, other types tend to be more numerous in the guts of those who are unwell. The presence of unhealthy bacteria is also associated with barrier problems in the lining of the intestines — a condition known as leaky gut.
In a recent paper, Kim makes the case that gut dysbiosis — the term microbiologists use to describe an unwell or out-of-whack microbiome — may allow the novel coronavirus to penetrate the gut’s lining, called the epithelium. “When the coronavirus leaks into the intestinal epithelium in a person with an altered gut microbiota, it can cause overactive immune responses that can make the situation worse by increasing inflammation,” Kim explains. In severe cases, the virus may even pass through the gut’s epithelial barrier and into the bloodstream, where it can then travel to the brain and other internal organs, wreaking havoc.
Kim cites several recent studies that have found people with Covid-19 tend to have lower bacterial diversity and fewer healthy gut microbes than people who do not have Covid-19. He also points out that a fat-heavy, fiber-deficient diet is a major risk factor for gut dysbiosis. These unhealthy dietary patterns and their attendant medical conditions tend to be much more prevalent in the West than in other parts of the world.
“We know that people with comorbid chronic conditions like hypertension and Type 2 diabetes are at increased risk for severe [Covid-19] disease, and we also know that pro-inflammatory microbes are more common in [the guts of] people with these conditions.”
In short, Kim believes that unhealthy diets and unwell microbiomes may explain why Covid-19 has taken such a heavy toll in the United States and some other wealthy nations. He acknowledges that there are gaps in the existing research that need to be filled in order to substantiate his premise. But his microbiome hypothesis makes sense and has some solid preliminary evidence to back it up.
If Kim’s ideas are borne out, they could open up new and game-changing avenues for Covid-19 detection, prevention, and treatment. But other gut experts say that, while worthy of more research, there are reasons to believe that the microbiome is just one piece in the Covid-19 puzzle.
The microbiome-immune connection
Emeran Mayer, MD, PhD, is a microbiome expert and co-director of UCLA’s Digestive Diseases Research Center. He’s been paying close attention to the work linking gut health to Covid-19 outcomes.
“It’s intriguing,” he says. “We know that people with comorbid chronic conditions like hypertension and Type 2 diabetes and hyperlipidemia are at increased risk for severe [Covid-19] disease, and we also know that pro-inflammatory microbes are more common in [the guts of] people with these conditions.”
The stomach and intestines are the immune system’s primary headquarters. “The majority of the immune cells are located right underneath the epithelial layer of the gut,” Mayer explains. And there’s mounting evidence that a range of health issues, many of which seem to have little to do with the GI tract, are affected by immune cells that reside or were once housed in the gut. For example, research in the journal Frontiers in Neurology has found that a person’s risk for stroke has a relationship with the composition of that person’s microbiome. “The outcome at the brain level is based in part on the experience of these immune cells as gut residents,” Mayer says.
Think of the immune cells in the gut as soldier-sentinels on the lookout for trouble. When unhealthy bacteria populate their environment, these soldier-sentinels become skittish and trigger-happy and more likely to respond to threats with excessive force—that is, inflammation. At the same time, poor microbiome health may allow virus molecules easier access to these skittish immune cells — both in the GI tract and elsewhere in the body.
The foods a person eats (or doesn’t eat) can contribute to both microbiome dysbiosis and the development of metabolic diseases like obesity. Even in people who are not obese or diabetic, Mayer says an unhealthy diet may shift the makeup of the microbiome in ways that unbalance the body’s immune responses, which may lead to worse outcomes. (By some recent estimates, only 12% of American adults are metabolically healthy.) Old age, a history of antibiotic use, and perhaps also an overly sanitized, largely indoor existence also seem to be risk factors for compromised gut microbiome health.
It’s wrong to conclude that jiggering a person’s microbiome is the key to solving the Covid-19 crisis.
“A lot of these risk factors are more common here in the U.S. than in places like India or Africa, where there’s less Covid,” Mayer says.
All of this evidence lends credence to the idea that the health of a person’s microbiome may be a significant determinant of their risk for severe Covid-19. In a recent BMJ study, researchers also speculated that by overpriming the immune system’s inflammatory response, imbalances in the microbiome could contribute to brain fog, fatigue, and other persistent post-viral symptoms that some have dubbed “long-haul Covid.”
But while all of these pieces fit together, Mayer says it’s wrong to conclude that jiggering a person’s microbiome is the key to solving the Covid-19 crisis.
He says the health of a person’s microbiome is often a reflection of that person’s overall health. And so the research linking unhealthy microbiomes to severe Covid-19 could be viewed as mere confirmation of something doctors already know — that people who have metabolic disease or conditions such as high blood pressure are at greater risk for a severe infection.
Still, the microbiome-Covid research points to some things people can do now to potentially lower their coronavirus risks.
Healthy diet, healthy gut, healthy immune system
Korea University’s Kim has speculated that fecal transplant procedures, which introduce healthy bacteria into an unhealthy person’s GI tract, could be effective in treating severe Covid-19.
“It’s an intriguing hypothesis, but I think it goes too far,” Mayer says. A wide range of medical conditions are associated with gut dysbiosis, he explains, but so far fecal transplant has only proved effective in treating a very few gut-specific ailments. He also doubts that probiotics — supplements packed with healthy bacteria — would do much good. There again, the hype has tended to outpace the science.
On the other hand, Mayer and Kim agree that improving one’s diet could meaningfully improve a person’s health at multiple levels — microbial, immune, metabolic — and so could offer some protection against Covid-19.
“We know that eating a variety of plant foods improves gut health and increases the production of short-chain fatty acids, an important group of anti-inflammatory mediators,” Mayer says. Also, fermented foods — kimchi, sauerkraut, kombucha, etc. — are packed with healthy bacteria. Eating a variety of them (not just guzzling kombucha) seems to support microbiome health, he adds.
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Meanwhile, Kim emphasizes the importance of fiber — especially from plant foods. “Daily consumption of a large amount of dietary fiber is an excellent way to build a healthy gut,” he says. He recommends eating 25 to 30 grams every day — advice that Mayer also endorses. Beans, lentils, berries, and whole grains are all good sources.
Outside of diet tweaks, almost anything that is good for a person’s overall health also seems to be good for the microbiome. Research has found that exercise, a good night’s sleep, and stress-reduction techniques such as mindfulness all benefit gut microbiome health.
“I think this microbiome-Covid research is fascinating, but the immediate clinical consequences are limited,” Mayer adds. “There are a lot of moving parts to this, and it’s difficult to say which is the chicken and which is the egg, or which elements are causative.”