Sweet n Sour: A Common Sugar May Help Pathogens Conquer the Human Gut
When fighting battles in the gut, pathogens that cause food poisoning may have a secret weapon. Natural ubiquitous sugar may help invading bacteria defeat the body’s natural microbiota.
Emerging work looking at the role of one common sugar in the body, fucose (not to be confused with fructose), suggests that it may play an essential handmaiden role for certain harmful bacteria. A new study from the U.S. Department of Energy’s Pacific Northwest National Laboratory (PNNL) in Richland, Wash., for example, finds that during Salmonella infection the pathogen may use fucose to fortify itself and find its way through a host’s body
This study, published in PLoS ONE, is just the latest suggesting that fucose may play a more central role in the delicate dance between invading pathogens and the gut’s commensal (resident) bacteria than previously thought. Earlier animal studies found that fucose can help tip the balance against commensal bacteria when pathogens including Escherichia coli and Campylobacter jejuni start spreading in the gut. Although the fucose findings are still preliminary, unlocking the role of this sugar in competitions between gut microbiota and pathogens could theoretically give rise to new therapies for treating human illness.
Some 100 trillion microorganisms reside in the human gut, where they perform essential tasks for immune defense, metabolism and development. Disruptions in that ecosystem can wreak havoc on health. When a pathogen like Salmonella invades the body, for example, it causes the immune system to react, and the gut becomes inflamed and kills off some of the body’s natural microbiota. In that vacuum Salmonella apparently seizes unused sugar that is normally tapped by the bodily gut bacteria, scavenging the sugar for nutrients and perhaps cues for action as well, according to this new work.
In this study researchers looked at how Salmonella colonized the bodies of mice that were genetically modified to be uniquely susceptible to the pathogen. (Most mice are not prone to gastrointestinal infection from Salmonella.) The researchers studied the impact of the disease in real time by gathering regular fecal samples from the infected mice and scouring them for clues about the makeup of the gut and the status of the infection. The team also performed autopsies on the infected mice and peered into the guts of deceased mice. For comparison the team also analyzed mice in a control group that were given a placebo instead of Salmonella infection. They studied the chemical fingerprints cellular processes leave behind and other genetic and structural components to get the first complete snapshot of the resident bacteria, proteins and sugar levels during Salmonella infection. Moreover, they were alerted to previously unknown functions of fucose in the course of infection.
The researchers are still trying to understand why they detected higher-than-normal fucose levels in Salmonella-infected mice. They know there were less commensal bacteria to dine on the fucose, but there may have been additional higher levels of fucose because cells damaged in the course of inflammation may release the sugar. Whatever the reason for its abundance, the team says the value of their study is that they were able to trace the real-time impacts of Salmonella infection in the gut. In the complex milieu of the gut it is challenging to pick up Salmonella proteins, so the researchers were skeptical they would even be able to track the infection. “Not only did we see the Salmonella proteins,” says study author Josh Adkins, a systems biologist at PNNL, “We saw a lot of them and hints of new biology.”
The team was surprised to discover that Salmonella ignored some sugars that resident bacteria eat while gobbling up fucose. This dietary preference may give drug-makers clues as to how to keep pathogens like Salmonella at bay. “You can imagine flushing someone’s body with a set of nutrients that can promote outgrowth of community members and prevent Salmonella from outcompeting them,” Adkins says. “I think that’s really where there is a lot of room for study.”
The PNNL findings are just the first step, says Vanessa Sperandio, a microbiologist at the University of Texas Southwestern Medical Center in Dallas who studies pathogen interaction in the gut. Researchers must next knock out fucose utilization genes in Salmonella to see if the pathogen can still outcompete microbiota in the gut without the sugar, she says. Depending on the findings, researchers will have a better sense of how important fucose may be when Salmonella takes on the gut’s resident bacteria.
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