Impressive new research from a team at Stanford University has revealed that a molecule produced by a certain type of gut bacteria can offer natural protection from Salmonella infections. As well as pointing toward potential new treatment strategies, the discovery could explain why some people get sicker from the pathogen than others.

Salmonellosis is a common bacterial infection, primarily caused by consuming food or water contaminated with Salmonella. Every year, millions of people around the world are struck down by the pathogen, and while most can recover within a few days, a number of people are inevitably hospitalized. What causes the sometimes dramatic differences in infection impact from person to person has been a mystery to scientists.

"Humans differ in their response to exposure to bacterial infections," says Denise Monack, senior author of the paper. "Some people get infected and some don't, some get sick and others stay healthy, and some spread the infection while others clear it. It has been a real mystery to understand why we see these differences among people."

The research was originally sparked by an observation showing two different strains of laboratory mice displaying varying levels of Salmonella in their guts. After extensive work the researchers discovered that a singular family of bacteria, called Bacteroides, seemed to be more abundant in the animals that displayed lower levels of Salmonella.

A key feature of Bacteroides is their ability to produce a variety of short-chain fatty acids, and the researchers noticed that one compound, propionate, was found in particularly high levels in the mice more resistant to Salmonella infection. Interestingly, further research revealed that propionate acted to suppress the growth of Salmonella in an entirely unexpected way.

Initially the researchers suspected propionate worked to protect against Salmonella in much the same way as other short-chain fatty acids, by improving immune system functions. But it was observed that propionate actually suppresses Salmonella growth by decreasing the intracellular pH inside the bacterium, which subsequently slows its ability to divide and replicate.

"Collectively, our results show that when concentrations of propionate, which is produced by Bacteroides, in the gut are high, Salmonella are unable to raise their internal pH to facilitate cellular functions required for growth," explains lead author on the study, Amanda Jacobson.

Moving forward, the researchers are set to further examine how propionate works on a molecular level and also try to identify other compounds produced by gut bacteria that could protect against infections from pathogens. It is yet to be shown whether a human clinical outcome would involve simply offering patients propionate as a treatment, but the researchers do note that this study does suggest general antibiotic treatments for Salmonella could make the infection worse by destroying healthy gut bacteria that can protect against infections.

The research was published in the journal Cell Host & Microbe.

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