A brand new UC Davis Well being research has uncovered how Salmonella micro organism, a significant reason behind meals poisoning, can invade the intestine even when protecting micro organism are current. The analysis, printed within the Proceedings of the Nationwide Academy of Sciences, explains how the pathogen tips the intestine surroundings to flee the physique’s pure defenses.
The digestive system is residence to trillions of micro organism, a lot of which produce short-chain fatty acids (SCFAs) that assist struggle dangerous pathogens. However Salmonella manages to develop and unfold within the intestine, though these protecting compounds are current. The research asks: How does Salmonella get round this protection?
“We knew that Salmonella invades the small gut, though it’s not its major web site of replication. The colon is,” mentioned the lead writer of the research Andreas Bäumler. Bäumler is a UC Davis distinguished professor and vice chair of analysis within the Division of Medical Microbiology and Immunology.
Bäumler and his group found that the reply lies in how the pathogen adjustments the intestine’s nutrient stability. When Salmonella enters the small gut, it causes irritation within the intestine lining and disrupts the traditional absorption of amino acids from meals. This creates an imbalance in vitamins within the intestine.
The imbalance offers Salmonella the sources it must survive and multiply within the massive gut (colon), the place useful micro organism normally curb its development. The research confirmed that salmonella causes irritation within the small gut to be able to derive vitamins that gasoline its replication within the colon.
Salmonella alters intestine nutrient surroundings to outlive
Utilizing a mouse mannequin, the group regarded carefully at how Salmonella modified the chemical make-up of the intestine. They traced amino acid absorption within the small and huge intestines.
They discovered that in mice that had been contaminated with Salmonella, there was much less absorption of amino acids into the blood. In truth, two amino acids, lysine and ornithine, turned extra considerable within the intestine after an infection. These amino acids helped Salmonella survive by stopping the growth-inhibiting results of SCFAs. They did this by restoring Salmonella’s acidity (pH) stability, permitting the pathogen to bypass the microbiota’s defenses.
“Our findings present that Salmonella has a intelligent means of adjusting the intestine’s nutrient surroundings to its benefit. By making it more durable for the physique to soak up amino acids within the ileum, Salmonella creates a extra favorable surroundings for itself within the massive gut,” Bäumler mentioned.
Within the research, the group confirmed that Salmonella makes use of its personal virulence components (illness inflicting molecules) to activate enzymes that break down key amino acids like lysine. This helps the pathogen keep away from the SCFAs’ protecting results and develop extra simply within the intestine.
New insights may result in higher intestine an infection therapies
The brand new insights doubtlessly clarify how the intestine surroundings adjustments throughout inflammatory bowel issues , similar to Crohn’s illness and ulcerative colitis, and will result in higher therapies for intestine infections. By understanding how Salmonella adjustments the intestine surroundings, researchers hope to develop new methods to guard the intestine microbiota and forestall these infections.
“This analysis makes use of a extra holistic method to learning intestine well being. It not solely offers us a greater understanding of how Salmonella works, but in addition highlights the significance of sustaining a wholesome intestine microbiota,” mentioned Lauren Radlinski, the research’s first writer and postdoctoral fellow within the Bäumler Lab. “Our findings may result in new therapies that assist help the microbiota throughout an infection.”
The research’s outcomes may encourage future therapies, together with probiotics or dietary plans designed to strengthen the physique’s pure defenses towards dangerous pathogens.
“By studying how a pathogen manipulates the host’s system, we will uncover methods to spice up the host’s pure defenses,” Radlinski mentioned.
Co-authors of the research are Andrew Rogers, Lalita Bechtold, Hugo Masson, Henry Nguyen, Anaïs B. Larabi, Connor Tiffany, Thaynara Parente de Carvalho and Renée Tsolis of UC Davis.
Extra info: Lauren C. Radlinski et al, Salmonella virulence components induce amino acid malabsorption within the ileum to advertise ecosystem invasion of the massive gut, Proceedings of the Nationwide Academy of Sciences (2024). DOI: 10.1073/pnas.2417232121