If You're Hungry When Sick, It Might Be Less Severe—But More Contagious

Lack of appetite often signals a cold or flu. Eating can be the last thing we want to do when we have a sore throat or are too fatigued or achy to even get out of bed. When hungry, we don't feel as strong as when we are well fed—and we more than likely aren't as strong.

The scientific world used to think that's how bacteria worked, too. When bacteria had ample nutrients available—when we were feeding that cold instead of starving a fever—they were healthier and would multiply, flourish, and keep on infecting. But a provocative new study published today in Cell has found a tricky Salmonella typhimurium bacteria that has evolved a mechanism that keeps humans it infects healthier—and makes the bacteria weaker.

Of course, there's more to the story, and it actually works to the bacteria's advantage.

The Basics of Salmonella

Salmonella infections can cause severe intestinal distress in humans and can be easily transmitted by ingesting food contaminated with the bacteria or by inadvertently passing it from our hands to our mouths, say, from handling pets infected with the bacteria.

Many types of Salmonella can cause diarrhea, fever, and abdominal cramps within 72 hours of infection. Usually the illness lasts less than a week and resolves on its own with fluid and electrolyte replacement. Some people's symptoms are so bad that they require hospitalization—and some people have died from Salmonella infections.

Salmonella outbreaks are fairly common. The most recent outbreak reported by the Centers for Disease Control and Prevention (CDC) was of 21 people in eight states infected with Salmonella heidelberg between January and October 2016. Eight of the infected people were hospitalized, and no deaths were reported. The outbreak was traced to contact with dairy bull calves purchased from livestock markets in Wisconsin.

In 2015, 907 people from 40 states were infected with Salmonella Poona. Before the outbreak was over, 204 people were hospitalized and six people died. Bacteria on cucumbers imported from Mexico were identified as the likely source of the outbreak.

In the Cell publication, a team of researchers from The Salk Institute for Biological Studies in California used mice to demonstrate that Salmonella typhimurium can make a trade-off between their own virulence (how sick the bacteria makes their host) and how easily it passes on to others (the transmission rate).

Feed a Cold or Starve Bacteria?

S. typhimurium infection occurs via a sequence of events. Once the organism is ingested, the bacteria penetrate the cells that line the gut, and immune cells like T and B lymphocytes rush in to help fight the infection. The bacteria that make it through travel through the blood and lymphatic system to other organs, like the liver and spleen.

Immune cells secrete a cytokine—a small protein called interleukin 1 beta (IL-1ß)—as a type of communication. IL-1ß sends a signal to the hypothalamus in the brain where appetite control resides, and the cytokine tells the brain to decrease appetite—a common sickness symptom.

The study team found that normal Salmonella made a protein that they called SlrP that prevented the bacteria's host from from making IL-1ß properly. They directly compared mice infected with this normal Salmonella to those infected with a lab strain of Salmonella that didn't make SlrP.

Mice infected with the SlrP-producing Salmonella stayed hungry, lost significantly less body weight, and 80% of them were healthy at 12 days. On the other hand, only 15% of mice infected with Salmonella that didn't make SlrP were healthy by then.

The trick? The healthier mice shed more of the bacteria for a longer time in their feces than the sicker mice. This bacteria was then ready and available to infect new hosts—spreading the sickness further through the community.

On the other hand, the Salmonella without SlrP were also more dangerous: More of these bacteria infected the spleen and liver than in mice than did the normal Salmonella.

The bacteria making SlrP had made a trade-off, basically, letting the host survive so that it could infect others, at the expense of their own virulence and spread within the body.

Evolutionarily, "increased pathogen virulence may come at a cost for Salmonella typhimurium transmission," study author Janelle Ayres, of the Salk Institute, wrote in the paper.

If the more virulent bacteria makes the host so sick that they die, the infection may die out before it passes to someone else. The bacteria has sealed its own reproductive and infective fate. But Salmonella had found a way around that.

This didn't come as a surprise to the researchers. "When an infection in the host affects appetite, the microbiome is also potentially compromised by the loss of nutrition. I expect to find that the microbiome has evolved strategies to block this sickness response," said Ayres.

In this study, Ayres and her team found that the Salmonella had done just that. By evolving a mechanism to block the IL-1ß, they prevented the lack of appetite. Better fed hosts resulted in better transmission of the bacteria.

It's not clear when the bacteria resort to this trade-off or what this means for human infections, but perhaps future treatments of infections will include nutritional therapy.

Maybe the old adage to starve a fever wasn't so far off.