New Insights Into Salmonella’s Ability to Manipulate the Gut Microbiota

Salmonella, a leading source of food poisoning, can enter the gut even in the presence of beneficial bacteria, according to a recent study from the University of California Davis Health. The study described how the pathogen manipulates the gut environment to evade the body's defenses and was published in the journal Proceedings of the National Academy of Sciences.

Trillions of bacteria reside in the digestive tract, and many of them generate short-chain fatty acids (SCFAs), which aid in the defense against dangerous pathogens. But despite the presence of these defense mechanisms, Salmonella can proliferate and disseminate throughout the gut. How does Salmonella circumvent this barrier, the study asks?

We knew that Salmonella invades the small intestine, although it is not its primary site of replication. The colon is.”

Andreas Bäumler, Distinguished Professor, Vice Chair and Study Lead Author, Department of Medical Microbiology and Immunology, University of California Davis

Bäumler and his colleagues found that the pathogen's alteration of the gut's nutritional balance holds the key to the solution. The normal absorption of amino acids from food is disrupted and the gut lining becomes inflamed when Salmonella reaches the small intestine. In the intestines, this leads to a nutritional imbalance.

In the large intestine (colon), where good bacteria often prevent it from growing, the imbalance provides Salmonella with the resources it needs to live and thrive. According to the study, Salmonella inflames the small intestine to obtain nutrients that support its colon proliferation.

Salmonella Alters the Gut Nutrient Environment to Survive

The scientists thoroughly examined how Salmonella altered the chemical composition of the stomach using a mouse model. They followed the small and large intestines' absorption of amino acids.

They discovered that mice infected with Salmonella had reduced blood absorption of amino acids. Indeed, following infection, the gut's levels of two amino acids lysine and ornithine rose. These amino acids prevented the growth-inhibiting effects of SCFAs, which allowed Salmonella to survive. By re-establishing the acidity (pH) balance of Salmonella, they were able to circumvent the microbiota's defenses.

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.”

Andreas Bäumler, Distinguished Professor, Vice Chair and Study Lead Author, Department of Medical Microbiology and Immunology, University of California Davis

The researchers demonstrated in the study that Salmonella activates enzymes that degrade essential amino acids like lysine by using its virulence factors, or disease-causing chemicals. This facilitates the pathogen's growth in the gut and helps it evade the protective effects of SCFAs.

New Insights Could Lead to Better Gut Infection Treatments

Better treatments for gut infections may result from these discoveries, which may also help explain how the gut environment changes during inflammatory bowel diseases like Crohn's disease and ulcerative colitis.

Researchers want to create novel strategies to safeguard the gut microbiota and stop these illnesses by comprehending how Salmonella alters the gut environment.

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. Our findings could lead to new treatments that help support the microbiota during infection.”

Lauren Radlinski, Study First Author and Postdoctoral Fellow, University of California Davis

The findings of the study may influence future therapies, such as probiotics or food regimens intended to boost the body's defenses against dangerous infections.

“By learning how a pathogen manipulates the host’s system, we can uncover ways to boost the host’s natural defenses,” Radlinski said.