Can fasting ward off infections? Mice study reveals an unexpected link

It starts with sick days and usually ends in some form of soup: Whenever we’re so ill that just looking at food makes us queasy, it seems like there’s always someone around telling us to eat more.

But the days of old adages like “feed a cold, starve a fever” might be numbered — at least if you ask the research team behind a study released Thursday in the journal PLOS Pathogens.

Researchers found not eating can help ward off infections by preventing the over-inflammation that comes with an immune response. At least, it did in mice.

What they found expands on our understanding of how fasting and the microbiome influence immune response to infection. In the future, the findings may also help in treating inflammatory conditions.

“I think this highlights that the response we normally have during infections — to stop eating —is the right one, and maybe we should even go a little bit further,” Bruce Vallance tells Inverse. “Don't try to feed your child if they're sick. If they don't feel like eating, just leave them alone.”

Vallance is the senior author of the study and a professor in the division of gastroenterology in the department of pediatrics at the University of British Columbia.

Here’s the background — Vallance said he hadn’t done much work in fasting until a student from Germany convinced him to try it in mice. “In Europe, fasting is very popular,” Vallance says.

They subsequently noticed that when mice were kept from eating and then infected with a pathogen, the infection didn’t “work.”

“If there are no extra nutrients available, the pathogen can't do anything.”

This counters conventional wisdom that when you lose your appetite, you should eat more.

“There's a lot of belief that the natural sickness responses are somehow bad for you,” Vallance says.

Adding to the confusion is the fact that previous research has been mixed, finding that not eating in response to infection can be protective in some cases, but make it worse in others, like bacterial sepsis or viral infection.

“But in general, I think we've evolved such that our natural responses are usually protective,” says Vallance.

How the discovery was made — Over the course of five years, Vallance and colleagues put lab mice in various groups and infected test groups with bacteria in combination with other conditions.

“There was such a dramatic effect on the infection.”

They started with a pathogen belonging to the genus Salmonella and infected the mice during periods of on-and-off fasting. The first infected test groups were compared with control groups who either didn’t fast or weren’t infected. The test groups included:

• Mice who fasted for 24 hours, got infected, and then fasted another 24 hours
• Mice who got infected then fasted for 48 hours

Then, the mice were euthanized and the contents of their gastrointestinal tract were examined to see how the pathogen had spread and interacted with their immune systems. They found:

• Mice who had fasted 24 hours before were essentially protected from the salmonella infection: They had virtually no gastroenteritis and no invasion of gut-lining cells.
• However, the fasting didn’t protect against the infection spreading to other parts of the body where it could cause some damage, but likely not trigger a strong inflammatory response (what’s behind most of the unpleasant effects of infection).

The mice that fasted before and after infection were protected because of a lack of nutrients to provide energy.

“There was such a dramatic effect on the infection,” Vallance says. “The invading pathogen coming in, they couldn't find anything to really grow or infect, or trigger the infection.”

The team also tested to see how the salmonella would react with and without fasting when the mice were given an antibiotic, just as we would if we got a bacterial infection. They found:

• The antibiotic still depleted a portion of the mice’s microbiota
• This indicated that fasting didn’t seem to make an antibiotic less effective

They wanted to know whether or not the microbiome was involved, so they infected germ-free mice (with no microbiomes) with salmonella after a fast and found they had less severe gastroenteritis. However, salmonella still invaded cells lining the gut.

This suggests that the microbiome helped suppress the harmful inflammatory response that accompanies gastroenteritis with fasting, though the pathogen was still present.

To make sure fasting wasn’t just protecting from salmonella, they performed similar with one other bacteria and found fasting still suppressed other bacterial infections and inflammatory responses in the intestines.

Why it matters — The results seem to indicate that when we lose our appetite during an infection, it’s probably best to go with our gut.

The immune system, Vallance says, is picking up on signals to stop eating - which may not stop the first infection’s progress, but won’t make it any worse.

There’s probably an adaptive angle to this.

“I think it's evolutionarily based on us hanging around some deer or something that we killed,” said Vallance. “If the first person gets sick or starts feeling bad, they shouldn’t go back and eat more of that contaminated food.”

But whether or not we can prevent infections by fasting — as mice can — is not yet known.

Mice immune systems are like ours if you put the remote on fast-forward. Whatever works in mice must be expanded to a much longer timeline for humans (if at all).

“If someone fasted for two weeks, and then were infected with salmonella, I think they'd be protected,” Vallance says. “But nobody's going to do that study.”

We also can’t anticipate infections weeks ahead of time — and you need to eat.

“I think the more translational part is we saw a reduction in inflammation,” Vallance says.

The pathogen had no nutrients to use for energy in the gut and with limited nutrients, the gut has less energy to trigger an inflammatory immune response — the one that’s responsible for most of the unpleasant side effects of an infection, like diarrhea.

Even in a microbiome-free environment, the absence of nutrient-sequestering microbes didn’t change much: the pathogen still only had few nutrients to feed off of.

“If there are no extra nutrients available, the pathogen can't do anything,” Vallance says. “When we're eating normally, we're leaving some energy behind that the pathogen can use to infect us.”

What's next — Vallance says the reduction in inflammation could hold promise for treating autoimmune diseases, where too much inflammation is a problem.

He’s currently collaborating with scientists in Germany to study how fasting could affect the microbiome’s role in inflammation and, in turn, conditions like diabetes and rheumatoid arthritis.

In the future, testing fasting’s protective effects on other bacteria, and studying the mechanisms behind the gut microbiome’s response to pathogens in the absence of food, could inform exactly how this information can serve people.

Vallance is curious about the specific microbes that play the biggest role and which inflammatory cells are involved. “A lot of people are doing clinical fasting studies looking at the immune system,” he says. “I think you have to do that in combination with the other inhabitants of the body.”

Abstract: Reducing food intake is a common host response to infection, yet it remains unclear whether fasting is detrimental or beneficial to an infected host. Despite the gastrointestinal tract being the primary site of nutrient uptake and a common route for infection, studies have yet to examine how fasting alters the host’s response to an enteric infection. To test this, mice were fasted before and during oral infection with the invasive bacterium Salmonella enterica serovar Typhimurium. Fasting dramatically interrupted infection and subsequent gastroenteritis by suppressing Salmonella’s SPI-1 virulence program, preventing invasion of the gut epithelium. Virulence suppression depended on the gut microbiota, as Salmonella’s invasion of the epithelium proceeded in fasting gnotobiotic mice. Despite Salmonella’s restored virulence within the intestines of gnotobiotic mice, fasting downregulated pro-inflammatory signaling, greatly reducing intestinal pathology. Our study highlights how food intake controls the complex relationship between host, pathogen and gut microbiota during an enteric infection.