A brand new UC Davis Well being examine 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 methods the intestine surroundings to flee the physique’s pure defenses.
The digestive system is dwelling to trillions of micro organism, a lot of which produce short-chain fatty acids (SCFAs) that assist battle dangerous pathogens. However Salmonella manages to develop and unfold within the intestine, despite the fact that these protecting compounds are current. The examine asks: How does Salmonella get round this protection?
“We knew that Salmonella invades the small gut, though it isn’t its main web site of replication. The colon is,” mentioned the lead writer of the examine 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 workforce 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 conventional absorption of amino acids from meals. This creates an imbalance in vitamins within the intestine.
The imbalance offers Salmonella the assets it must survive and multiply within the massive gut (colon), the place helpful micro organism often curb its development. The examine confirmed that salmonella causes irritation within the small gut with a purpose to derive vitamins that gas its replication within the colon.
Salmonella alters intestine nutrient surroundings to outlive
Utilizing a mouse mannequin, the workforce regarded intently 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 actual fact, two amino acids, lysine and ornithine, turned extra ample 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 approach of fixing 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 examine, the workforce confirmed that Salmonella makes use of its personal virulence elements (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 remedies
The brand new insights doubtlessly clarify how the intestine surroundings adjustments throughout inflammatory bowel issues , akin to Crohn’s illness and ulcerative colitis, and will result in higher remedies 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 examine’s first writer and postdoctoral fellow within the Bäumler Lab. “Our findings may result in new remedies that assist help the microbiota throughout an infection.”
The examine’s outcomes may encourage future remedies, together with probiotics or dietary plans designed to strengthen the physique’s pure defenses in opposition to dangerous pathogens.
“By studying how a pathogen manipulates the host’s system, we are able to uncover methods to spice up the host’s pure defenses,” Radlinski mentioned.
Co-authors of the examine 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 elements induce amino acid malabsorption within the ileum to advertise ecosystem invasion of the big gut, Proceedings of the Nationwide Academy of Sciences (2024). DOI: 10.1073/pnas.2417232121