A new UC Davis Health study uncovers how Salmonella bacteria manipulate gut nutrients to circumvent natural defenses, offering new insights for tackling gut infections.
Researchers at UC Davis Health have unveiled a clever mechanism that Salmonella bacteria use to overcome the gut’s natural defenses and cause infections. The study, published in the Proceedings of the National Academy of Sciences, sheds light on how this common foodborne pathogen manipulates its environment to survive and replicate in the intestines.
“We knew that Salmonella invades the small intestine, although it is not its primary site of replication. The colon is,” lead author Andreas Bäumler, a distinguished professor and vice chair of research in the Department of Medical Microbiology and Immunology at UC Davis, said in a news release.
Typically, the digestive system houses trillions of beneficial bacteria that produce short-chain fatty acids (SCFAs), which fight harmful pathogens. Despite these protective compounds, Salmonella manages to thrive.
The UC Davis team asked, “How does Salmonella get around this defense?”
The answer lies in how Salmonella alters the gut’s nutrient balance. Upon entering the small intestine, the bacteria cause inflammation in the gut lining, disrupting normal amino acid absorption from food and creating an imbalance of nutrients. This shift enables Salmonella to thrive in the colon, an environment typically controlled by beneficial bacteria.
Using a mouse model, the researchers traced amino acid absorption in both the small and large intestines during infection. They found that two amino acids, lysine and ornithine, became more abundant in the gut, aiding Salmonella by counteracting SCFAs’ growth-inhibiting effects. The increased presence of these amino acids allowed Salmonella to restore its acidity (pH) balance and evade the defenses of the gut microbiota.
“Our findings show that Salmonella has a clever way of changing the gut’s nutrient environment to its advantage. By making it harder for the body to absorb amino acids in the ileum, Salmonella creates a more favorable environment for itself in the large intestine,” Bäumler added.
Moreover, the study revealed that Salmonella employs its virulence factors to activate enzymes that break down key amino acids like lysine, aiding its survival and replication in the gut.
The implications of this discovery extend beyond combatting Salmonella infections. The insights gained could inform better treatments for inflammatory bowel disorders, such as Crohn’s disease and ulcerative colitis, by protecting the gut microbiota and preventing infections.
“This research uses a more holistic approach to studying gut health. It not only gives us a better understanding of how Salmonella works, but also highlights the importance of maintaining a healthy gut microbiota,” first author Lauren Radlinski, a postdoctoral fellow in the Bäumler Lab, said in the news release. “Our findings could lead to new treatments that help support the microbiota during infection.”
Future treatments inspired by this study might include probiotics or dietary plans aimed at bolstering the body’s natural defenses against pathogens.
“By learning how a pathogen manipulates the host’s system, we can uncover ways to boost the host’s natural defenses,” Radlinski added.