A new study from UC Davis Health has discovered how Salmonella bacteria, a leading cause of food poisoning, can invade the intestine even when protective bacteria are present. The research, published in the Proceedings of the National Academy of Sciencesexplains how the pathogen tricks the intestinal environment to escape the body’s natural defenses.
The digestive system is home to trillions of bacteria, many of which produce short-chain fatty acids (SCFAs) that help fight harmful pathogens. But Salmonella manages to grow and spread in the intestine, even though these protective compounds are present. The study asks: How does Salmonella avoid this defense?
“We knew that Salmonella invades the small intestine, although it is not its main site of replication. The colon is,” says the study’s lead author, Andreas Bäumler. Bäumler is a UC Davis Distinguished Professor and vice president for research in the Department of Medical Microbiology and Immunology.
Bäumler and his team discovered that the answer lies in how the pathogen changes the nutrient balance of the intestine. When Salmonella enters the small intestine, it causes inflammation in the lining of the intestine and disrupts the normal absorption of amino acids from food. This creates a nutrient imbalance in the intestine.
The imbalance provides Salmonella with the resources it needs to survive and multiply in the large intestine (colon), where beneficial bacteria often slow its growth. The study showed that salmonella causes inflammation in the small intestine to obtain nutrients to drive its replication in the colon.
Salmonella alters the intestinal nutrient environment to survive
Using a mouse model, the team looked closely at how Salmonella changed the chemical composition of the intestine. They tracked the absorption of amino acids in the small and large intestines.
They found that in mice infected with Salmonella, there was less absorption of amino acids into the blood. In fact, two amino acids, lysine and ornithine, became more abundant in the intestine after infection. These amino acids helped Salmonella survive by preventing the growth-inhibiting effects of SCFAs. They did this by restoring the acidity (pH) balance of Salmonella, allowing the pathogen to evade the microbiota’s defenses.
“Our findings show that Salmonella has a clever way of changing the nutrient environment of the intestine to its advantage. By making it more difficult for the body to absorb amino acids in the ileum, Salmonella creates a more favorable environment for itself in the large intestine,” Bäumler saying.
In the study, the team showed that Salmonella uses its own virulence factors (disease-causing molecules) to activate enzymes that break down key amino acids such as lysine. This helps the pathogen avoid the protective effects of SCFAs and grow more easily in the intestine.
New insights could lead to better treatments for intestinal infections
The new insights potentially explain how the intestinal environment changes during inflammatory bowel disorders, such as Crohn’s disease and ulcerative colitis, and could lead to better treatments for intestinal infections. By understanding how Salmonella changes the intestinal environment, researchers hope to develop new ways to protect the intestinal microbiota and prevent these infections.
“This research uses a more holistic approach to studying gut health. Not only does it give us a better understanding of how Salmonella works, it also highlights the importance of maintaining a healthy gut microbiota,” said Lauren Radlinski, first author of the study and postdoctoral fellow. in the Bäumler laboratory. “Our findings could lead to new treatments that help maintain the microbiota during infection.”
The study results could inspire future treatments, including probiotics or dietary plans designed to strengthen the body’s natural defenses against harmful pathogens.
“By learning how a pathogen manipulates the host system, we can discover ways to stimulate the host’s natural defenses,” Radlinski said.
Co-authors of the study are Andrew Rogers, Lalita Bechtold, Hugo Masson, Henry Nguyen, Anaïs B. Larabi, Connor Tiffany, Thaynara Parente de Carvalho and Renée Tsolis of UC Davis.