A recent study reveals how Salmonella, a leading source of foodborne illnesses, can infiltrate the gut even when there are protective bacteria present.
A new study from UC Davis Health has shed light on how Salmonella bacteria—a well-known cause of food poisoning—can penetrate the gut even amid the presence of protective bacteria. This research, published in the Proceedings of the National Academy of Sciences, details how the bacteria cleverly manipulate the gut environment to evade the body’s defenses.
The digestive system hosts trillions of bacteria, many of which generate short-chain fatty acids (SCFAs) that help combat harmful pathogens. Nevertheless, Salmonella succeeds in thriving and proliferating within the gut, despite these protective substances. The study investigates how Salmonella circumvents this defense.
According to lead author Andreas Bäumler, a distinguished professor and vice chair of research in the Department of Medical Microbiology and Immunology at UC Davis, “We previously understood that Salmonella invades the small intestine, while its primary replication occurs in the colon.”
Bäumler and his research team found the answer in how the bacteria alter the nutrient dynamics within the gut. When Salmonella enters the small intestine, it triggers inflammation in the gut lining, disrupting the normal absorption of amino acids from ingested food. This disruption leads to a nutrient imbalance in the gut.
This imbalance provides Salmonella with the means to survive and thrive in the colon, an area where normally beneficial bacteria would restrain its growth. The research indicated that Salmonella induces inflammation in the small intestine to obtain nutrients necessary for its replication in the colon.
Salmonella modifies the gut nutrient environment for survival
The research team utilized a mouse model to meticulously observe how Salmonella altered the chemical composition of the gut, monitoring amino acid absorption in the small and large intestines.
They discovered that in mice infected with Salmonella, amino acid absorption into the bloodstream was significantly reduced. In particular, two amino acids—lysine and ornithine—were found in increased amounts within the gut after infection. These amino acids helped Salmonella endure by negating the growth-limiting effects of SCFAs. They achieved this by restoring the acidity balance (pH) of Salmonella, enabling it to escape the microbiota’s protective measures.
“Our research indicates that Salmonella has a sophisticated method of altering the nutrient landscape of the gut to benefit itself. By making it more challenging for the body to absorb amino acids in the ileum, Salmonella cultivates a more suitable environment for itself in the colon,” Bäumler noted.
The study revealed that Salmonella employs its own virulence factors (molecules that cause disease) to activate enzymes responsible for breaking down crucial amino acids like lysine. This mechanism helps the bacteria evade the protective effects of SCFAs and facilitates its growth within the gut.
New insights may enhance treatments for gut infections
The study’s findings potentially clarify how the gut environment alters during inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, which could lead to improved treatments for gut infections. Understanding how Salmonella modifies the gut environment may allow researchers to devise innovative strategies to support the gut microbiota and prevent these infections.
“This research employs a more comprehensive approach to understanding gut health. It not only enhances our understanding of Salmonella’s operations but also emphasizes the significance of sustaining a healthy gut microbiota,” asserted Lauren Radlinski, the study’s first author and postdoctoral fellow in Bäumler’s lab. “Our discoveries could pave the way for new treatments aimed at supporting microbiota during infections.”
The results of the study may inspire future strategies, such as probiotics or dietary interventions aimed at fortifying the body’s innate defenses against harmful pathogens.
“By uncovering how a pathogen manipulates its host, we can identify ways to enhance the natural defenses of the host,” Radlinski concluded.
Co-authors of this study include Andrew Rogers, Lalita Bechtold, Hugo Masson, Henry Nguyen, Anaïs B. Larabi, Connor Tiffany, Thaynara Parente de Carvalho, and Renée Tsolis from UC Davis.
