New study shows how salmonella tricks gut defenses to cause infection

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, revealed within the Proceedings of the Nationwide Academy of Sciences, explains how the pathogen methods the intestine setting to flee the physique’s pure defenses.

The digestive system is dwelling to trillions of micro organism, lots of which produce short-chain fatty acids (SCFAs) that assist battle dangerous pathogens. However Salmonella manages to develop and unfold within the intestine, though 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,” stated 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 crew found that the reply lies in how the pathogen modifications 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 provides Salmonella the assets it must survive and multiply within the massive gut (colon), the place useful micro organism normally curb its progress. The examine confirmed that salmonella causes irritation within the small gut so as to derive vitamins that gas its replication within the colon.

Salmonella alters intestine nutrient setting to outlive

Utilizing a mouse mannequin, the crew appeared 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 have 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 means of adjusting the intestine’s nutrient setting to its benefit. By making it tougher for the physique to soak up amino acids within the ileum, Salmonella creates a extra favorable setting for itself within the massive gut,” Bäumler stated.

Within the examine, the crew 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 might result in higher intestine an infection remedies

The brand new insights probably clarify how the intestine setting modifications throughout inflammatory bowel issues , resembling Crohn’s illness and ulcerative colitis, and will result in higher remedies for intestine infections. By understanding how Salmonella modifications the intestine setting, 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 provides us a greater understanding of how Salmonella works, but in addition highlights the significance of sustaining a wholesome intestine microbiota,” stated Lauren Radlinski, the examine’s first writer and postdoctoral fellow within the Bäumler Lab. “Our findings might result in new remedies that assist assist the microbiota throughout an infection.”

The examine’s outcomes might encourage future remedies, 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 stated.

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.