AMES, Iowa — Researchers in the Department of Food Science and Human Nutrition at Iowa State University have discovered an innovative approach to fight bacteria and their antimicrobial resistance in poultry by exploiting linkages between the gut neurochemical and immune systems.
Poultry products are the primary vehicle for exposure to the foodborne disease, Salmonella, in the United States. More than 1 million infections represent approximately $400 million in costs each year. Extensive efforts have been made to minimize the incidence of this harmful pathogen in poultry via antimicrobial drugs, but the spread of resistant genes has fostered emergence of antibiotic-resistant strains. Other approaches, such as using vaccines or probiotics, have had disappointing results.
Salmonella establishes early in chicks’ intestines, as the natural microbiota is getting established. It persists by suppressing the birds’ natural inflammatory responses, allowing this pathogen to freely colonize the chicken intestine. Often the birds show no sign of infection, which prevents identification of infected animals.
A new study at Iowa State shows potential to fight Salmonella using natural interactions between the chickens’ nervous and immune systems, which coalesce in the gut. In the work, reported this month in the scientific journal “Nature: Communications Biology,” the researchers showed they could use the drug Reserpine to improve gut health by inducing dramatic changes in intestinal immunity and metabolism. This drug triggers release of the naturally occurring neurochemical, norepinephrine, from intestinal cells, which then activates an antimicrobial immune response at a level that significantly reduced the incidence of Salmonella and other potentially harmful intestinal bacteria.
The research was led by Melha Mellata, associate professor in the Department of Food Science and Human Nutrition at Iowa State, and Graham Redweik, a recent doctoral student in the Interdepartmental Microbiology Graduate Program at Iowa State, now at the University of Colorado-Boulder. Redweik worked on the project in Mellata’s laboratory with support from a predoctoral fellowship from the U.S. Department of Agriculture National Institute of Food and Agriculture. Other contributors included Mark Lyte in the Department of Veterinary Microbiology and Preventive Medicine at Iowa State; Ryan Arsenault in the University of Delaware Department of Animal and Food Sciences; and Michael Kogut with the USDA-Agricultural Research Service.
“This research is important because of the emergence of more antibiotic resistant pathogens,” Redweik said. “We were looking for different antimicrobial strategies to overcome resistance, but we came up with the idea to take a slightly different approach. Reserpine is a drug commonly used in humans to treat high blood pressure, but it hasn’t been used much in livestock. Finding it can turn on a therapeutic response gives us hints of new ways to address these threats and avoid over-dependence on antibiotics in commercial agriculture.”
To analyze the new approach, the researchers looked at the treatment’s effectiveness on the chickens’ cells and organs in the lab and on live animals. In all cases, the drug was able to significantly knock down the incidence of several strains of Salmonella, as long as it was administered early, before the pathogen could colonize the chicks’ intestines.
“Using this approach is really about stimulating the host’s ability to fight the infection on its own and solve the problem at its source,” Mellata said. “I believe this is the first time this neurochemical pathway has been identified as a way to fight Salmonella. We’re looking at this as a model first and foremost. These systems and the routes between them are complex. There might be other drugs or other ways to take advantage of this pathway, but this is a promising first step.”
The researchers suggest their work may have implications to help control other diseases.
“Looking ahead, it will be interesting to test other animal models that are also major reservoirs for food pathogens to see if this approach has potential for widespread use,” Redweik said.