The prevalence of allergic diseases is increasing worldwide, but little progress has been made in preventing them. Epidemiologic studies have identified strong associations between early life farming exposures and protection from developing allergic diseases. This project aimed to better define the important environmental exposures and immune signatures in providing protection from developing allergic disease. This project established a novel birth cohort including infants born into animal farming environments and traditional old world agrarian lifestyles. Researchers identified key differences between the immune cells and microbial communities of infants that were related to farming lifestyles. These findings are now being leveraged and integrated into a more expansive, NIH-funded project designed to build upon these research findings.
The Challenge
The prevalence of allergic diseases is increasing worldwide. Asthma is the most common chronic disease of childhood and affects 1 in 10 children in Wisconsin. Racial minorities and urban dwellers are disproportionately affected by asthma, and these differences are largely attributable to environmental factors. Advancements have been made in the treatment of asthma and other allergic diseases, but little progress has been made in preventing allergies in the first place.
The inception of allergic diseases typically occurs during early childhood and leads to chronic, lifelong disease. Previous research indicates that early exposures to environmental microbes like bacteria, viruses, and fungi promote the maturation of infants’ immune system and consequently reduce the risk of allergic disease. Exposure to environmental microbes, in turn, increases the diversity of an individual’s gut microbiome which describes the trillions of microbes that live in the intestinal tract. These gut microbes produce metabolites that alter the development of immune cells and impact the risk for the development of allergies.
Project Goals
The researchers’ goal was to better define the important environmental exposures and immune signatures in providing protection from allergic disease. Specifically, researchers hypothesized that exposure to microbes like bacteria in a farm setting would result in unique patterns in gut microbial-associated metabolites in early life which influence immune cell maturation trajectories and profiles that are related to protection from allergic diseases.
This hypothesis was addressed through three specific aims. First, they sought to characterize how farm-related exposures relate to immune development in early life. Second, researchers planned to define the microbial-associated metabolite profiles in early life stool. Third, they aimed to define group-specific associations between metabolomic, microbial, and immune profiles to identify differences between the distinct study groups of traditional agrarian lifestyles (Amish), farm, and non-farm infants.
Results
The researchers were successful in reaching their goal through outcomes relating to immune development in early life and the composition of the gut microbial community. First, transcriptomic studies were used to define gene expression differences in the immune cells between study groups. This data showed notable differences in innate immune cells called monocytes between Amish and both farm and non-farm newborns. Next, researchers optimized a multiparameter flow cytometry panel to extensively characterize multiple immune cells. Finally, studies of stool samples from 2-month-old infants showed distinct microbial community structure and function between the study groups. Amish infants were found to have an increased abundance of a bacteria called Bifidobacterium longum which plays an important role in stimulating the immune system.
Looking to the Future
The findings from this novel birth cohort study are being used as preliminary data for an NIH grant proposal aimed at extending this work and exploring the relationship between monocyte training in early life and gut microbial exposures.
