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CAGED: Making food safer

Jan. 28, 2020: An international interdisciplinary project led by EPI investigator Arie Havelaar seeks to identify bacterial causes of enteric dysfunction and chronic gut inflammation in Ethiopian children. By studying complex interactions between livestock and people, the project aims to identify reservoirs and exposure pathways by which Campylobacter bacteria colonize kids. But interventions are the ultimate goal.

CAGED: Making food safer

Globally, the most common cause of bacterial gastroenteritis in people is a genus of spiral- and rod-shaped bacteria known as Campylobacter. The World Health Organization estimates that 166 million people a year are sickened by this pathogen. Campylobacter bacteria are among the most frequent causes of diarrheal disease globally.

Diarrheal disease is a leading cause of malnutrition for children younger than five. Frequent bouts of diarrhea, or repeated gut infections in the absence of diarrhea, are increasingly recognized as important risk factors for stunting, or impaired growth. This condition encompasses more than just height; children with stunting face a suite of factors that may last a lifetime. Stunted kids are at increased risk for having poor cognitive capacity and lower educational outcomes, they even go on to experience lowered wages as adults and are at increased risk of chronic diseases such as obesity and diabetes.

Arie Havelaar, a professor in UF’s Institute of Food and Agriculture’s animal sciences department, wants to improve the health and nutrition of children growing up in low- and middle-income countries, where stunted growth and malnutrition is still common. The bacteria occur naturally in the digestive tract of livestock, such as poultry and cattle and can be transmitted to humans by a myriad of pathways including food, water, soil and direct contact with animals.

Although less than one percent of children living in the U.S. may be colonized with Campylobacter bacteria at any time, Havelaar says that it would not be unusual to find communities in Ethiopia where 50 to 75 percent may harbor these bacteria.

These bacteria, along with other gut microbes, are associated with environmental enteric dysfunction, which is characterized by chronic gut inflammation. In affected individuals, the finger-like absorptive surface of the gut, the villi, become flattened. This hinders the body’s ability to efficiently absorb nutrients. The barrier function of the gut may also be compromised, and bacteria may get access to cause systemic infection, which further compromises a child’s health.

“The tight junctions between the cells become leaky,” Havelaar says. “Which means that all sorts of bacteria can move from the gut environment into systemic circulation, which then causes further inflammation.” 

Havelaar, who is affiliated with the Emerging Pathogens Institute, is leading a project in Ethiopia called CAGED, or Campylobacter Genomics and Environmental Enteric Dysfunction, which seeks to learn which livestock reservoirs are the most important for the transmission dynamics of these bacteria, and the pathways by which children become exposed. Funding from the Bill and Melinda Gates Foundation supports the work, by cosponsoring the U.S. AID Feed the Future Innovation Lab for Livestock Systems. The ultimate goal is to design interventions which might boost the children’s overall health and wellbeing.

In the U.S., Campylobacter infections are almost exclusively associated with diarrheal disease, but in Africa the majority of those carrying it will not become ill. “This has always intrigued me,” Havelaar notes. “We figure perhaps acquired immunity plays a role and protects individuals from developing disease; but this only prevents illness, it does not keep the bacteria from establishing in the gut.”

While the two most common Campylobacter species associated with illness, C. jejuni and C. coli, are well known to science, the CAGED project is “detecting a host of other species, and these can truly be considered emerging,” Havelaar says.

The project is being carried out in close collaboration with researchers at Haramaya University, Ethiopia, one of whom recently visited UF. Yitagele Mekonnen Terefe is a veterinarian and researcher at Haramaya University, who says he became involved in CAGED since its beginning because stunted growth poses so many cascading risks for large swaths of the world’s children, and because of his interest in the role of zoonotic pathogens such as Campylobacter. Terefe is also a visiting scholar at The Ohio State University where he is undergoing laboratory training and creating capacity building links between all three universities.

“This is such an important pathogen for Ethiopia, but also for other countries,” says Terefe, who visited UF Jan. 15-17 and participated in the Institute for Sustainable Food System’s Future of Food Forum.

Yitagele Terefe, left, and Arie Havelaar, right.

Using molecular techniques, Terefe (at left, above) and Havelaar (at right) are guiding efforts to determine which domestic animals may be the most common reservoir for exposing kids to Campylobacter. They are also testing fecal samples from children and the animals in their households to analyze which Campylobacter species are most associated with environmental enteric dysfunction.

“We will culture the fecal samples on media that are suitable for the growth of different species of Campylobacter bacteria,” Terefe says. “Then we incubate them for 48 hours and characterize them by advanced molecular techniques such as whole genome sequencing. The other technique we use is where we extract the bacteria DNA and use real-time polymerase chain reaction tests to identify the presence of Campylobacter genes. We will also characterize the gut microbiome by metagenomic sequencing.”

“We are currently designing a study to look in much more detail at the reservoirs of these bacteria,” Havelaar says. “Where do they grow? Which kinds of animals? We also are interested to know if there is human-human transmission involved.”

Terefe and Havelaar initially thought chickens would be implicated as an important exposure pathway for children. But their work has shown that cattle, goats and possibly other animals may also play a role. Once they understand the pathways, the research team can then develop a suite of hygiene recommendations to minimize exposure.

“If for example, raw milk is a pathway that brings the bacteria from cattle to chicken to children, then obviously the intervention would be different than if the kids pick up soil and are exposed that way,” Havelaar says.


Creator Credits

Written by DeLene Beeland

Top photo: Medical illustration of Campylobacter by Alissa Eckert and publicly available on the CDC PHIL database.

Bottom photo: Yitagele Terefe (left) and Arie Havelaar (right) at the Emerging Pathogens Institute building on UF's campus in January 2020. Photo courtesy of Havelaar.

 

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Read Arie Havelaar's bio here.