The Unhealthy Alliance of Salmonella and Gut Yeast

Researchers at the University of Illinois Chicago have uncovered a concerning interaction between the common gut yeast Candida albicans and the bacterium Salmonella Typhimurium, revealing how this relationship can enhance Salmonella's ability to infect and spread within the body. The findings, published in the journal Nature, indicate that a specific protein produced by Salmonella, known as SopB, can stimulate the yeast to release arginine, a crucial amino acid that boosts Salmonella's invasive capabilities while dampening the host's inflammatory responses.

Gut microbes are essential for human health, influencing various functions such as immune responses, digestion, and interactions with other microorganisms. While much research has focused on bacteria, the roles of fungi and viruses in gut health remain less understood. Alterations in the composition of the gut mycobiome have been associated with several gastrointestinal diseases, yet the interactions between fungi and bacteria during infections are still largely unexplored.

Non-typhoidal Salmonella is one of the most significant enteric pathogens, affecting approximately 100 million individuals annually. In healthy individuals, infections typically present as localized inflammatory diarrhea, but those with weakened immune systems face more severe risks, including the potential for the bacteria to disseminate to other organs.

In their study, the researchers examined how Candida albicans affects Salmonella colonization and systemic spread. They utilized various mouse models, including those pre-treated with antibiotics and germ-free mice. The team also conducted in vitro experiments using human colonic epithelial cell lines.

The experiments involved two main approaches: one where mice were treated with antibiotics before being colonized with Candida albicans, and another where they were first colonized without antibiotics. The researchers monitored the mice for Salmonella levels in the gut, as well as its spread to other organs like the spleen and liver over a 72-hour period. They also assessed weight loss and other health indicators.

In laboratory settings, the human colonic cell lines were exposed to Salmonella in the presence of live Candida albicans at a specific ratio, and various assays were conducted to measure microbial binding and invasion capabilities. This included genetic tests that investigated the roles of specific Salmonella genes in the binding and invasion processes.

The results demonstrated that the presence of Candida albicans significantly increased Salmonella loads in the gut and facilitated its entry into the bloodstream. Mice co-infected with both organisms exhibited greater weight loss and increased Salmonella dissemination compared to those infected with Salmonella alone. Furthermore, the analysis revealed that arginine levels were elevated in co-cultures, and the addition of arginine enhanced Salmonella's invasion capabilities.

The study concluded that Candida albicans colonization may act as a risk factor for Salmonella infection, with arginine serving as a critical metabolite bridging the interactions between the yeast, the bacterium, and the host. The researchers noted that the presence of Candida albicans during Salmonella infections in humans is not well-documented. However, a referenced study indicated a significant increase in recurrent Salmonella infections among patients colonized with the yeast. The authors suggest that antifungal therapies could be a potential avenue for preventing infections in susceptible populations.