BEAMS ABSTRACT: OverallPrevalence of childhood asthma has significantly increased in the last decades and one potential explanationfor this upsurge is decreased exposure to protective environmental microbes due to improvements in sanitationand use/overuse of antimicrobial products during pregnancy and early life. In support of this contention severalstudies in isolated rural communities have reported lower prevalence of asthma among children of animalfarmers more heavily exposed to environmental microbes than among their non-farmer peers. If theseobservations are applicable to more mainstream US populations is unknown. We recently observed that MexicanAmerican children living in Tucson Arizona have a prevalence of childhood asthma that is fourfold higher thanin Nogales Mexico. This dramatic difference in rates of asthma suggests that even in this limited geographicregion and among an ancestrally similar population differential exposures may exist which account for relativeprotection against asthma in Mexico. Tucson is only 70 miles north of Nogales Mexico which is a 200k inhabitantcity located just south of the US-Mexico border. Nogales Mexico lacks public sanitation facilities and povertyrates are very high. In preliminary data we observed marked differences in microbial communities present indust drinking water and in stools of one-month-old children between the two cities. Based on these findingswe propose the Binational Early Asthma and Microbiome Study (BEAMS). The BEAMS overall goals are: toidentify divergent early-life microbial and immune developmental trajectories associated with asthma protectionin Nogales Mexico compared with Tucson Arizona and the environmental factors that promote them; to isolatethe specific microbes genes and their products that confer such protection; and to ascertain the mechanisms bywhich these microbial communities or their products promote asthma protection. To accomplish these goalsBEAMS will have three Projects and four Cores. We will enroll 250 pregnant mother/offspring dyads of Mexicanancestry in each city. We will thoroughly assess environmental microbial exposure maternal gut microbiota andmicrobial gene expression maternal immune markers and meconium microbiome. We will relate thesecharacteristics to childs fecal microbiome and metabolome in early life to asthma-related immune markers inthe childs blood as assessed by mass cytometry analysis and single cell epigenetic and gene expressionstudies and to asthma-related clinical phenotypes by age 2 years. We will also assess in mouse models thespecific molecular mechanism that explain the protective effects against the development of childhood asthmaof specific microbial strains and metabolites present in Nogales Mexico. We expect BEAMS to offer a betterunderstanding of the early origins of asthma and new asthma prevention strategies applicable to Mexican-Americans and potentially to all Americans.