Th188 - Relationship of Early Farm Exposure on the Trajectory of Innate Immune Cell Function and Gut Microbiome

Abstract Text: A protective association between early life animal farming exposure and development of allergic disease has been widely reported. Several reports have demonstrated increased pro-inflammatory blood immune features in farm-exposed newborns. The cell origins of the pro-inflammatory signals, the trajectory of immune phenotypes in early life, or associations with gut microbial communities in early life farm-exposed children has not been studied.

Established in 2013, the Wisconsin Infant Study Cohort (WISC) is an ongoing birth cohort designed to further define the impact of early life farm exposure on immune development. Early life innate immune cell functions were measured by stimulating freshly isolated blood mononuclear cells with a panel of innate TLR agonists in animal farm exposed (n=73) and rural non-farm (n=96) children from birth to age 2. Flow cytometry and bead-based assays were used for immunophenotyping. Additionally, 16S rRNA sequencing was performed on serially collected stool samples within the first year. Mixed effects models were used to assess the trajectory of immune and microbiome variables.

Farm-exposed children had significantly increased LPS-specific responses (myeloid dendritic cell intracellular TNF (p=0.015), secreted IL10 (p=0.007) and MIP-1b (p=0.018)) compared to non-farm children during the first 2 years of life. The gut microbiomes of farm-exposed children were more diverse than non-farm children (p=0.012), especially at nine months of age. Random forest analysis identified farm-predictive microbes, which included short chain fatty acid producers.

These data show that farm-exposed children have a LPS-specific pro-inflammatory and regulatory immune trajectory in early life, alongside an increased rate of gut microbiome diversification.