Salmonella Typhimurium invading cultured human cells

These Salmonella bacteria may be able to make mice hungry

Rocky Mountain Laboratories, NIAID, NIH

Microbe that causes food poisoning exerts a sort of mind control over mice

When we have food poisoning, the last thing we want to do is eat. But in mice, a microbe that causes this ailment actually increases appetite, a new study reveals. Researchers say they might be able to use the same trick to increase eating in cancer patients and old folks, who often lose their desire for food. 

“I think it’s a fantastic paper,” says immunophysiologist Keith Kelley of the University of Illinois in Urbana, who wasn’t connected to the study. The researchers deserve praise for combining approaches from several disciplines such as microbiology, neurobiology, and immunology to draw a surprising conclusion, he says. “It’s the way disease responses should be investigated.”

Some of the symptoms you endure  when you are ill, such as lethargy and fever, are actually good for you. Lolling on the couch all day, for instance, saves energy for your immune cells. But the picture is more complex for another of these so-called sickness behaviors—reduced appetite. Animal studies have found that eating less seems to improve the odds of surviving some infections, perhaps because it robs the invading microbes of key nutrients, but in other cases the loss of appetite often proves fatal.

Immunomicrobiologist Janelle Ayres of the Salk Institute for Biological Studies in San Diego, California, and colleagues set out to determine how reduced eating affects a type of Salmonella bacterium that gives rodents a sometimes-fatal illness and causes food poisoning in people. After infecting mice with the microbes, Ayres and the researchers found that a bacterial protein called SlrP altered how dangerous the microbes were. Bacteria that didn't produce the protein were more likely to kill the rodents. Mice infected by the SlrP-lacking bacteria also ate about 20% less than did their peers, the team reports online today in Cell.

That result suggests that Salmonella bacteria use SlrP to manipulate the mice’s appetite. When the rodents come down with a Salmonella infection, the researchers found, the vagus nerve, which connects the brain to the gut, dispatches signals to the hypothalamus that spur the animals to cut back on eating. But SlrP blocks these signals.

So what’s in it for the bacterium? Salmonella microbes typically camp out in an animal’s small intestine. But the researchers found that if the animals aren’t eating, the bacteria also invade the liver, spleen, and other locations in the abdomen. When the microbes depart from the small intestine, they cause a more serious disease that is more likely to kill the mice. So by inducing the animals to eat, SlrP helps keep the bacteria in the small intestine and prevents them from killing the mice. If the rodents are alive and eating, they will also be excreting. Thus the bacteria are more likely to end up in the rodents’ poop, which gets eaten by other rodents, thus passing the bugs to a new host, the team found.

A pathogen that reproduces rapidly but kills its host won’t spread to many new hosts. So Salmonella has to balance how lethal it is with how readily it is transmitted. “It makes sense that the pathogen would try to be around the ‘sweet spot’” that increases its ability to infect new hosts, says disease ecologist James Adelman of Iowa State University in Ames, who wasn’t connected to the study.  

The work “highlights a novel way in which pathogens are able to get around this [sickness] response,” says biological anthropologist Eric Shattuck of the University of Texas (UT) in San Antonio. But neuroimmunologist Robert Dantzer of the UT MD Anderson Cancer Center in Houston is skeptical of the explanation for why the bacteria would sustain appetite. In the wild, the question is not whether a sick animal should eat, he says, but whether it should go out looking for food. “Sick individuals need to conserve energy for the metabolic requirements of the immune system.”  

Although sickness behaviors are usually beneficial, the study shows that one of these behaviors, eating less, is harmful in Salmonella infections—and it could be in other bacterial illnesses. Ayres says the results suggest that feeding patients might be useful for treating these types of infections. In addition, researchers might be able to duplicate the effects of the bacteria on appetite for other types of people who need to eat more, such as the elderly or those who are receiving cancer treatment.