A tale of two cities and a health mystery

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Imagine two children growing up just steps apart – one lives in Nogales, Sonora, Mexico, and the other lives minutes away in Nogales, Arizona. They share similar ancestry and genetics, yet the child on the United States side of the border is four times more likely to develop asthma. Why? 

Scientists at the University of Arizona Health Sciences Asthma and Airway Disease Research Center are hoping the answer to that question will be found in the Binational Early Asthma and Microbiome Study, or BEAMS. Researchers are following pregnant women and their babies to learn how early-life environmental exposures and factors such as dust, water and diet affect asthma risk.

“It’s a rare opportunity to study a genetically similar population that lives in uniquely different environments, allowing us to isolate how early-life exposures impact asthma risk,” said Tara Carr, MD, a professor of medicine at the U of A College of Medicine – Tucson and one of the co-principal investigators for BEAMS.

Investigating the hygiene hypothesis

BEAMS is led by Fernando Martinez, MD, director of the Asthma and Airway Disease Research Center, together with Donata Vercelli, MD, associate director of the center, Carr, Cecilia Rosales, MD, professor emeritus at the U of A Mel and Enid Zuckerman College of Public Health, and Susan Lynch, PhD, from the University of California, San Francisco. The study dives deep into the hygiene hypothesis, an idea that reduced germ exposure keeps a child’s immune system from developing the ability to naturally fight infectious organisms. 

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“Paradoxically, in the middle of all the poverty and underdevelopment in many ‘barrios’ and ‘colonias’ in Nogales, Sonora, there is less asthma,” Martinez said. “There is four times less asthma there than here, and our studies show the main reason is because, although children in Nogales, Sonora, are exposed to harmful bacteria that cause many infections, they are also exposed to a lot of protective bacteria that train their immune system to distinguish between dangerous and innocuous microbes.”

The foundational science that led to BEAMS included a study published in 2016 in which researchers surveyed 1,700 middle schoolers across Tucson, Nogales, Arizona, and Nogales, Sonora, using the International Study of Allergies and Asthma in Children questionnaire. 

“There was a mystery here,” said co-author Paloma Beamer, PhD, a professor and associate dean in the U of A Mel and Enid Zuckerman College of Public Health. “Despite Tucson’s cleaner air and different housing characteristics, children of Mexican descent in Tucson had four times the asthma prevalence of children in Nogales, Sonora, and were almost double the national rates of asthma in children. People assume air pollution is the biggest driver of asthma, but this suggested something more was at play.”

Beamer, who grew up bilingual and bicultural in both the U.S. and Mexico, has asthma and wondered if early exposures to diverse microbes could help explain the differences in asthma risk. 

In a subsequent study, the team swept house dust from homes in Tucson and Ambos Nogales on both sides of the Border. Tests showed U.S. dust differed vastly from Mexico dust, though the houses were steps apart.

The types of microbes in the dust, known as the dust microbiome, varied in relation to home environment characteristics such as the type of flooring, presence of air conditioning, or source of drinking water in the home. 

“The border is one of the largest divides between a wealthy nation and a low middle income nation,” Beamer said. “The results were striking to us.”

A cross-border quest for answers

The studies published by U of A Health Sciences researchers established a strong foundation for BEAMS, which is funded by a $15.3 million grant from the National Institute of Allergy and Infectious Diseases, a division of the National Institutes of Health. Through BEAMS, researchers are taking their investigations to the next level and hoping to answer the question, “Why are asthma risks different?”

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BEAMS uses three approaches – population, microbiological and mechanistic – to help unravel asthma risk. The cross-border study is following 500 children from before birth to age 5. Researchers are collecting blood and stool samples and airway swabs from participants, as well as water and dust samples from the environment.

The logistics of the study make the research both challenging and possible at the same time.

“The study is complicated and has been challenging,” said Carr, who noted that the study first opened amid the COVID-19 pandemic, which further complicated matters. “It is a full-time job for our research coordinators to collect and process everything. For many of our samples, it’s critical we have those processed within 24 hours, especially the samples coming from Mexico.”

Andrea Diaz Pacheco, a research coordinator for BEAMS, is responsible for transporting biological samples between the U.S. and Mexico. She picks up the samples from Mexican nurses at the Morley port of entry almost daily. The samples go through U.S. Customs and Border Patrol, with Centers for Disease Control and Prevention permissions, before they are delivered to a BIO5 Institute laboratory on the University of Arizona’s main campus in Tucson.

“It’s an enormous effort,” Carr said, “but the data we’re gathering is invaluable.” 

The team has collected more than 11,000 samples in the first three years of the study, and the preliminary data has been clear. Carr says babies in U.S. show higher rates of early illness, which can predict later asthma. In contrast, infants in Mexico develop richer, healthier gut microbial communities. The team is preparing to publish its latest findings.

“There are clear microbial differences,” Carr said. “We see distinct variations in home dust, diet, antibiotic use and even daycare attendance, all of which may be influencing immune development.”

Carr said another intriguing early finding involves diet. U.S. households are more reliant on processed foods, while families in Mexico consume more unprocessed foods such as beans and legumes. Carr believes that dietary differences, combined with varying microbial exposures in home environments, may be shaping immune responses from birth.

“Our goal is to pinpoint protective environmental factors that reduce asthma risk and find ways to apply them in the U.S.,” Carr said. “This research is relevant to a broader population. What we learn here could help shape public health policies and interventions that benefit children around the world.”