Don't Starve During Infections, Eat More

Highlights

• Infections can bring about changes like loss of appetite, fever, which is part of body's normal response to an illness.
• New study has demonstrated that consumption of extra calories despite appetite loss improves chances of survival.
• These extra calories, reduce the virulence of the bacteria, prevents its spread to other parts of the body and helps in speedy recovery.

Infections trigger behavioral changes in the host including anorexia or loss of appetite, fever and sleep disturbances. This loss of appetite as part of the body's normal response to an illness.

Though this response is not well understood, eating less during illness promotes a faster recovery most of the time. But in cases such as when cancer patients experience wasting, the loss of appetite can be deadly.

A new study by researchers from the Salk Institute shows the link between appetite and infection and how bacteria block the appetite loss response in their host to make the host healthier and also promote the bacteria's transmission to other hosts.

The findings could have implications in treating infectious diseases, infection transmission and appetite loss associated with illness, aging, inflammation or medical interventions (like chemotherapy).

"It's long been known that infections cause loss of appetite but the function of that, if any, is only beginning to be understood," says Janelle Ayres, assistant professor at Salk Institute's Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis.

Infections kill at least 23,000 people annually in the United States alone and around two million people become infected with bacteria that are resistant to antibiotics, according to the U.S. Centers for Disease Control.

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Promoting Appetite to Combat Infection

Researchers conducted experiments in mice by orally infected it with the bacteria Salmonella Typhimurium.

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As a normal defense response, they typically experienced appetite loss and eventually become much sicker as the bacteria become more virulent, spreading from the intestines to other tissues in the body.

On testing different conditions in the infected mice, researchers found that when sick mice consumed extra calories despite their appetite loss actually survived longer.

This survival was not due to a more active immune response by well-fed animals.

They found that the extra calories caused the Salmonella to become less virulent prevented it from spreading outside of the intestines and throughout the body. This enabled the animals to stay healthy despite infection.

Another finding was that the Salmonella were acting on the intestine to promote this condition by trying to suppress the appetite loss in the host.

The results showed that the bacteria were making a trade-off between virulence and transmission. Virulence is the ability of a microbe to cause disease within one host, and transmission is its ability to spread and establish infections between multiple hosts.

"What we found was that appetite loss makes the Salmonella more virulent, perhaps because it needs to go beyond the intestines to find nutrients for itself. This increased virulence kills its host too fast, which compromises the bacteria's ability to spread to new hosts," explains Sheila Rao, a Salk research associate and the first author on the study. "The tradeoff between transmission and virulence has not been appreciated before--it was previously thought that virulence and transmission were coupled."

The bacteria benefited when the host ate more and survived longer during infection as in those mice, they were able to spread via feces to other animals and increase its transmission between hosts, as compared to bacteria in mice who did not eat and died sooner due to heightened bacterial virulence.

How the Bacteria Halts Appetite-Loss Response

In order to halt the appetite-loss response and boost transmission between hosts, Salmonella produces a molecule called SlrP.

This molecule blocks the activation of an immune protein (cytokine) in the intestines. Cytokine promotes appetite loss in the host during infection by communicating with the brain's appetite center, called the hypothalamus.

The researchers found that mice infected with Salmonella that could not produce SlrP ate less food while infected, lost more weight and died faster than control mice.

Conclusion

Researchers caution that responses to infections are dependent on many factors and the effects of eating or fasting on health during an infection will depend on the causative agent.

"Now that we'd identified this mechanism that regulates appetite, we want to turn it on the flip side and see if we can decrease appetite via this mechanism to help in cases of metabolic disease," says Ayres.

Researchers plan to further explore the human microbiome, which is the collection of bacteria that live in people's bodies, to identify other microbes that might have a similar effect on this pathway and explore those for new therapies tied to appetite loss and treating disease.

They also want to investigate whether drugs could be used to target SlrP to turn up or down the sickness-induced appetite-loss pathway.

"Finding alternatives to antibiotics is incredibly important as these drugs have already encouraged the evolution of deadly antibiotic-resistant strains," says Ayres.

This findings are published in the journal Cell.

Reference

1. Janelle Ayres et al. Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission. Cell ; (2017) doi.org/10.1016/j.cell.2017.01.006

Source-Medindia