Illustration of Enterobacteriaceae bacteria. Individual bacterium are shown as pink rod shapes with ...

Mind and Body

The secret to treating Long Covid may lie in the gut microbiome

Bacterial populations may predict who gets Long Covid.

Alissa Eckert/SCIENCE PHOTO LIBRARY/Science Photo Library/Getty Images

When Covid-19 hit the world with a sucker punch, Siew C. Ng didn’t flinch. Her research experience on the gut microbiome and its role in immunity told her it’s likely involved in Covid-19 infection — but further, Ng hypothesized it could also help treat features of Covid-19. Now, in the journal Gut, Ng and her team report the fruit of their labor: They show how healthy gut bacteria could protect against Long Covid.

The gut microbiome is a significant regulator of the immune system — in turn, an imbalanced gut can impair the immune response, including injuring tissues and prolonging inflammation. Ng’s hunch that this mechanism may bear out in people with Covid-19 proved correct: In March 2020, her team found several ‘good’ bacteria missing from the gut of people with Covid-19 infection. Further, the missing gut bacteria were associated with the severity of Covid-19 illness. Ng is an associate director for the Center for Gut Microbiota Research and professor at The Chinese University of Hong Kong.

Ng suspected the gut microbiome might also play a role in why some people develop persistent symptoms even after the initial infection dissipates — Long Covid.

Long Covid: Who gets it?

Long Covid occurs when people who have cleared the coronavirus out of the body continue to exhibit symptoms for another four or more weeks. People with asymptomatic or mild infections are also vulnerable to Long Covid.

Long Covid manifests itself as a variety of symptoms. One study suggests more than 50 Long Covid symptoms, with the most common being fatigue, headache, attention disorder, hair loss, and shortness of breath. Just this week, researchers found evidence that Covid-19 can affect heart health a year after the infection.

There’s no exact cause of Long Covid, and there is no clear trend in whom is at risk — one in three people will develop Long Covid, and every person who has a Covid-19 infection runs the risk of developing long-term symptoms.

What’s new — In Ng’s study of 106 people who had been infected with Covid-19, 81.1 percent of them reported Long Covid symptoms after three months. By six months, 76.4 percent of the people reported having Long Covid.

To study the microbiome, the researchers analyzed stool samples to sequence and identify bacterial species living in the gut. Stool samples were collected one month and six months after hospital discharge. Because diet affects the gut microbiome, they also kept track of every participant’s dietary habits after leaving the hospital.

The most common symptoms after six months were:

  • Fatigue
  • Memory problems
  • Hair loss
  • Anxiety
  • Sleeping issues

Ng’s team found that the composition of the gut microbiome could determine whether a person developed Long Covid symptoms after recovery.

Stool samples from previously infected people showed a lower bacterial diversity in the gut after six months compared to people who were never infected with Covid-19. Further, the researchers observed an imbalanced microbiome with decreased Ruminococcus and Bifidobacterium bacterial species in previously infected people. Interestingly, whether these people had received antibiotics as part of their treatment didn’t make a difference. Something else was driving the loss of diversity.

Eating fermented food, like pickles, can help boost friendly gut bacteria.Yana Tatevosian / 500px/500Px Plus/Getty Images

“Friendly bacteria such as Bifidobacterium adolescentis and Bifidobacterium longum are important as they help boost immunity,” explains Ng to Inverse.

Instead, the microbiome compositions did differ based on whether a participant reported Long Covid symptoms. People who recovered from infection but did not have Long Covid experienced changes in 25 bacterial species. But their microbiome completely recovered after six months.

In contrast, people with Long Covid had decreases in 28 bacterial species. After six months, significant reductions were observed in:

  • Collinsella aerofaciens
  • F. prausnitzii
  • Blautia obeum

But in turn, people with Long Covid had higher amounts of Ruminococcus gnavus and Bacteroides vulgatus. The researchers also found people with Long Covid had different gut microbiomes depending on their symptoms.

“The most surprising findings were that different bacteria patterns were associated with different categories of Long Covid symptoms such as respiratory, neurological, gastrointestinal, hair loss, etc. Such patterns were characterized by a higher level of “unfriendly” microbes and lower levels of “friendly” microbes,” Ng says.

For example, patients who reported persistent respiratory symptoms after six months were associated with an increase in harmful pathogens, including:

  • Streptococcus anginosus
  • Streptococcus vestibularis
  • Streptococcus gordonii
  • Clostridium disporicum

Meanwhile, a lack of good bacteria, such as the Bifidobacteria species, which help boost the immune system, was strongly associated with persistent respiratory symptoms.

People with neuropsychiatric symptoms and fatigue were more likely to have higher Clostridium innocuum and Actinomyces naeslundii. Hair loss was linked to decreases in butyrate-producing bacteria such as Roseburia inulinivorans and Faecalibacterium prausnitzii.

Can the gut treat Long Covid?

As the world enters year two of the pandemic, scientists remain stumped on the exact cause of Long Covid and why only some people recovering from infection develop Long Covid while others don’t — the gut microbiome may be the key.

Proactively profiling an individual’s gut microbiome during a Covid-19 infection could help screen people at high risk for Long Covid. Tracing gut microbe diversity and changes to the microbiomt could give doctors a head’s up to take preventative action to repair microbial diversity and perhaps even make a difference in Long Covid outcomes.

It also gives people the opportunity to improve their gut microbiome by changing their diet or taking probiotics. Early research (that has not been peer-reviewed by experts) suggests taking a daily Lactobacillus rhamnosus GG probiotic may help prevent or delay Covid-19 symptoms when exposed to the virus.

Other ways to ensure a healthy and balanced gut are avoiding antibiotics and exercising. Ng says studies on fecal microbiota transplants are still underway but may help with replenishing low bacterial species in the gut.

Getting enough exercise can help maintain gut health, research suggests.yulkapopkova/E+/Getty Images

What’s next — There is currently no treatment for Long Covid. Still, Ng and her team are working on a microbiome immunity formula to correct any imbalances SARS-CoV-2 may cause to the gut microbiome.

Ng tells Inverse an ongoing pilot study testing the microbiome immunity formula has produced high-yielding results. People positive with Covid-19 and given the microbiome immunity formula have so far shown their symptoms resolve and an increase in antibody development.

Future work will also look into any specific diet that boosts the effectiveness of the microbiome immune formula to treat and prevent Long Covid. Research has shown that the gut microbiome thrives when people eat fermented food or a Mediterranean diet.

Ng is also studying a potential relationship between the gut microbiome and the Covid-19 vaccine. Regulating a healthy gut microbiome could enhance and optimize the Covid-19 vaccine response, too.

“Recently, we reported the first human study to provide evidence that gut microbiota modulates Covid-19 vaccine response in that people who lacked Bifidobacterium adolescentis in their gut had a lower antibody response to inactivated Covid-19 vaccine, and certain bacteria was associated with lower adverse effects in mRNA vaccines,” Ng says.

If effective, the gut microbiome could prove critical for boosting antibody responses after vaccination for high-risk individuals. Only time will tell, but Ng’s work is helping to break down the enigma of Long Covid and how to treat it.

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