Can a stomach bug cause long-term disease? From MS to cancer, new studies suggest the hidden danger of common infections
- Research links common bugs to Crohn’s disease, multiple sclerosis and more. But it depends on genetics, and studies are being carried out to find out more
- Scientists think long-term illnesses may be caused by an overreaction of some people’s immune system to certain bugs. Young women may be at a heightened risk
In most people, norovirus causes a few days of misery spent in the bathroom and then is quickly forgotten. Epstein-Barr virus can pass without any indication at all. And many people shrug off Covid-19.
But a growing body of research suggests that in some unlucky few, the immune system overreacts to these seemingly minor insults, leaving years or even a lifetime of symptoms.
“The wrong genetics with the wrong infection at the wrong time [can be dangerous],” says Dr Judith James, a rheumatologist and vice-president of clinical affairs at the Oklahoma Medical Research Foundation, in the United States. “I do think we have mounting evidence that means people should have this on their radar.”
It’s long been suspected that seemingly simple infections can leave a lasting imprint.
New research found a likely connection between a bout of norovirus – more commonly known as a stomach bug, which tends to strike mostly in winter in Hong Kong – and Crohn’s disease, a long-lasting inflammatory bowel condition.
Usually, a trigger occurs when a bug or drug looks to the immune system like one’s own cells or tissues, says Dr Raymond Chung, a liver specialist at Massachusetts General Hospital and Harvard Medical School, in the US. This mimicry spurs a response, and then the response perpetuates the problem.
Understanding how that cycle gets started and then is reinforced could lead to treatments, Chung says.
“If we could really catalogue those steps, then I think we would be in a better position to think about interruption of the cascade,” he says. Carefully dialling down the response will be key, because broadly blocking the immune reaction “could lead to unintended consequences”.
Even if people can’t avoid everyday pathogens, it’s important to identify the connections between them and long-term consequences, he says.
“Knowledge is power. It’s really for us to understand our own predispositions to these kinds of exaggerated, aberrant responses – but it will take time.”
Short-term illness, long-term misery
For decades, researchers have believed that infections could lead to long-term problems.
Chickenpox is known to reappear later in life as shingles, an extremely painful nerve disorder.
The 1918 flu pandemic – also known as Spanish flu – led some people to develop Parkinson’s disease.
But solid scientific evidence has been accumulating only in recent years, says Mark Davis, who directs the Stanford Institute for Immunity, Transplantation and Infection in California, in the US.
The mapping of both the human and mouse genomes has helped researchers understand the role of immune system genes at a deeper level, he says.
The research on norovirus used a mouse that had been given the same genetic mutation often connected with intestinal disease.
When infected with norovirus, the mouse’s immune system made T cells – a type of white blood cell that’s an essential part of the immune system – that damaged the gut, as expected. But it also prevented T cells from releasing a protective factor that would otherwise restore the gut. So the mouse was less able to recover from the infection.
Although it’s tough to prove the same thing happens in people, the study provides a plausible explanation for this infection-disease connection, says its senior author, Ken Cadwell – who studies how viruses interact with the immune system at the New York University Grossman School of Medicine, in the US.
On its own, the stomach bug is usually inconsequential, says Dr John Wherry, director of the Institute for Immunology at the University of Pennsylvania’s Perelman School of Medicine.
Some people have a genetic mutation that on its own is equally inconsequential. But when someone with a seemingly inconsequential mutation gets a seemingly inconsequential infection, it can disrupt the balance of bugs that live in their gut, leading to bowel disease.
It’s been hard to prove this sequence of events because the virus is gone by the time symptoms appear. Researchers have known that the gut microbe balance was out of whack, but it wasn’t shown until this new study that the instigator was a simple infection, he says. “It’s a trifecta combination. This is like a real ecosystem.”
But why are some people more vulnerable than others? It turns out genetics are a key factor in this disease cascade, but figuring out which genes cause vulnerability to which infections is no easy task.
“There are many diseases and each one is going to have a different set of molecules in play,” Davis says.
Overall, about one in 12 people will develop an autoimmune condition over the course of their lifetime, James says.
Young adult women are known to be particularly vulnerable to autoimmune diseases, though no one knows exactly why.
“Women often have slightly stronger immune responses, and that’s more noticeable during those child-bearing ages,” she says. Hormones may play a role, but this doesn’t fully explain the difference. “We don’t have all the answers.”
Anyone with an autoimmune disease in the family has a higher risk of developing an autoimmune disease themselves, she says. Identical twins, though, might or might not get an autoimmune disease if their twin does, or might develop it decades later. Autoimmune diseases can also be sporadic, cropping up without any obvious familial link.
Because these conditions rarely start at birth, there’s likely some kind of a tipping point that happens later on in life, such as an infection, she says. “Maybe you need either a lot of genetics and a little infection or a lot of infection and some of the genetics.”
Rather than identifying most people as high risk, it might be easier to quickly see when someone’s immune system is overreacting to an infection, she says.
Although these long-term symptoms might be an individual thing “between a particular bug, a particular person and maybe a particular moment in time”, there are common mechanisms across these conditions, Davis says.
Hopefully, that means scientists will eventually learn how to exploit these mechanisms to develop treatments.
“It’s becoming more and more clear how these diseases got started,” he says. “What isn’t clear is why they persist in particular people. Why doesn’t the system come back in balance again?”
Figuring that out and curing disease, “that’s the next chapter in all of this”.
Can you protect yourself?
“As an immunologist, I feel embarrassed [there isn’t one],” he says.
Davis scoffs at commercial “immune boosters”, saying that at best they separate people from their money, and at worst they might be harmful.
What’s really needed is for researchers to understand what makes someone more vulnerable to long-term consequences from infections, Chung says.
“Part of that is genetics. But part of that may also be understanding what your immune profile might be at any given moment in time. We can then ask, is this problematic? Is this a risk signature?”
Mounting evidence suggests that the microbiome – the bugs that live on and in everyone’s body – can influence the immune system. But it’s still too early to know what can be done to boost immune health through the microbiome, she says.
Though there’s little people can do to understand their own risk, researchers say it doesn’t make sense to panic.
“I’m not one to get hysterical about these things,” Wherry says. “Infections and microbes are part of our world, part of our life, part of a lifespan.”
“If you know that everyone in your friend’s family has been sick for the last week and they invite you over for dinner, maybe take a rain check for the following week,” he says.