Once restricted to the Eastern Hemisphere, the Chikungunya virus has infected millions of people across the Americas since 2013, when mosquitoes were discovered with the virus in the Caribbean. About half of all people infected with the Chikungunya virus never show symptoms, while some develop fever and joint pain that lasts for about a week, and 10% to 30% develop debilitating arthritis that lasts for months or years.
Scientists have understood little about why the severity of the disease varies so widely. A study by researchers at the Washington University School of Medicine in St. Louis shows that gut bacteria can play a role in mice. Research shows that mice with defective gut microbiomes were less able to control infection with the Chikungunya virus. In addition, giving a single type of bacteria – or a chemical compound produced by that type – improved the mice’s immune response, lowered the levels of virus in their blood, and decreased the likelihood that a mosquito that fed blood on infected mice would accumulate Virus.
The results, published July 14 in the journal Cell, suggest that having a healthy microbiome could help reduce the risk of severe Chikungunya disease and possibly even reduce its spread in the community by preventing the transmission of the Virus is disrupted from one person to a mosquito to another person.
“With many viral diseases, only a subset of infected people become symptomatic, and we don’t really understand why,” said senior author Dr. Michael S. Diamond, Professor of Medicine with Herbert S. Gasser. “There can be things that happen during your life that shape your immune system and affect whether you stop the infection early and have minimal symptoms or can’t stop it and develop serious illness. We found that mice don’t have a healthy gut microbiome, them Not only do they get sicker, but mosquitos that draw their blood are more likely to become infected. Promoting a healthy microbiome could be important not just for those who might become infected, but for the entire community to help cycle through to interrupt or shorten transmission. “
The gut microbiome is the community of bacteria that live in the gut. Gut bacteria metabolize and chemically modify some of the material that passes through the digestive tract, creating vitamins and other compounds as byproducts that are then absorbed by cells or other microbes. They help regulate inflammation and the body’s response to infection.
To find out whether the gut microbiome affects the severity of Chikungunya infection, Diamond, lead author Emma Winkler, a PhD student in Diamond’s laboratory, and colleagues studied mice without normal gut microbiomes. They used two types of mice: aseptic mice, which had been kept in sterile conditions since birth and therefore never developed an intestinal microbiome, and ordinary laboratory mice treated with a cocktail of two commonly used antibiotics to reduce the complexity of their intestinal microbiomes.
For comparison, the researchers infected groups of aseptic and antibiotic-treated mice with the Chikungunya virus and a group of laboratory mice with normal microbiomes. The virus multiplied and spread quickly in the mice lacking gut microbes, reaching high levels in the blood and tissues far from the site of infection. Further experiments showed that important immune cells were impaired in mice without a normal gut microbiome.
The introduction of just one species of bacteria – a normal member of the human gut microbiome known as Clostridium scindens – saved the mice’s ability to fight the infection. C. scindens is typically not found in mice. But it’s common in humans where it modifies a bile acid produced in the liver and creates a compound that affects immune cells. When the researchers gave the modified bile acid alone to mice lacking normal microbiomes, it improved their immune response and decreased the virus levels in the blood and tissues.
“If an unhealthy microbiome affects the levels of viruses in your blood, it begs an interesting question for a blood-borne pathogen: Does the health of your microbiome affect the transmission?” said Diamond, who is also a professor of molecular microbiology and pathology and immunology. “Obviously, if there are more viruses in the blood, a mosquito is more likely to get infected during a blood meal.”
To test this idea, Diamond and Winkler infected three groups of mice with the Chikungunya virus. One group was treated with antibiotics to eliminate their gut bacteria, a second was treated with antibiotics and later treated with C. scindens to repopulate such bacteria in the gut, and the third group was given no antibiotics at all so they had normal gut microbiomes had . The researchers took blood a day after the infection and offered the blood to the mosquitoes to feed on. More than half of the mosquitoes that drew blood from antibiotic-treated mice became infected, compared to less than a third of mosquitoes that fed on the mice’s blood on normal microbiomes or on C. scindens only.
“There are a lot of people walking around with unhealthy microbiomes and varying amounts of conjugated bile acids in their gut,” Diamond said. “There may be other bacteria that are even better than C. scindens at modifying bile acids that could be used to balance microbiomes. If such a probiotic were created it could be a way of not only minimizing disease in individuals but to reduce community spread at the same time. “