Biomarkers of Development of Immunity and Allergic Diseases in Farming and Non-farming Lifestyle Infants: Design, Methods and 1 Year Outcomes in the “Zooming in to Old Order Mennonites” Birth Cohort Study

Abstract

Traditional farming lifestyle has been shown to be protective against asthma and allergic diseases. The individual factors that appear to be associated with this “farm-life effect” include consumption of unpasteurized farm milk and exposure to farm animals and stables. However, the biomarkers of the protective immunity and those associated with early development of allergic diseases in infancy remain unclear. The “Zooming in to Old Order Mennonites (ZOOM)” study was designed to assess the differences in the lifestyle and the development of the microbiome, systemic and mucosal immunity between infants born to traditional farming lifestyle at low risk for allergic diseases and those born to urban/suburban atopic families with a high risk for allergic diseases in order to identify biomarkers of development of allergic diseases in infancy. 190 mothers and their infants born to Old Order Mennonite population protected from or in Rochester families at high risk for allergic diseases were recruited before birth from the Finger Lakes Region of New York State. Questionnaires and samples are collected from mothers during pregnancy and after delivery and from infants at birth and at 1–2 weeks, 6 weeks, 6, 12, 18, and 24 months, with 3-, 4-, and 5-year follow-up ongoing. Samples collected include maternal blood, stool, saliva, nasal and skin swabs and urine during pregnancy; breast milk postnatally; infant blood, stool, saliva, nasal and skin swabs. Signs and symptoms of allergic diseases are assessed at every visit and serum specific IgE is measured at 1 and 2 years of age. Allergic diseases are diagnosed by clinical history, exam, and sensitization by skin prick test and/or serum specific IgE. By the end of the first year of life, the prevalence of food allergy and atopic dermatitis were higher in ROC infants compared to the rates observed in OOM infants as was the number of infants sensitized to foods. These studies of immune system development in a population protected from and in those at risk for allergic diseases will provide critical new knowledge about the development of the mucosal and systemic immunity and lay the groundwork for future studies of prevention of allergic diseases.

Skin tape‐strips in old order Mennonite toddlers reveal upregulated barrier markers and low T‐helper inflammatory tone

“…Our analysis captured key overlapping markers between OOM versus ROC with or without AD, such as SNX5 and IL17D, and distinct markers as shown in OOM infants bathed less frequently than ROC (p <.05). 2 We found highly significant correlations between bathing frequency and skin biomarkers related to asthma severity, such as RNF182, SEPTIN1, and SCN7A, as well as those implicated in asthma, AD, or Th2 allergic inflammation, including LRTM1 and CSF1R (all r >0.85 and p <.05; Table S3). 12 We also observed significant negative correlations with Th2 suppressive marker BACH2 (r =−0.9) and skin barrier maintenance markers (GRHL1, PDCD6IP, r = −0.8) (all p <.05; Table S3).…”

“…1 Research has shown that children raised on farms experience lower rates of atopic conditions, with serum-based studies suggesting an association between early life environmental exposure and distinct immune development patterns. [2][3][4][5] Nevertheless, there is limited insight into how farming lifestyle may impact skin biomarker expression and protect against atopy. Old Order Mennonites (OOM) are among the rural communities that have been studied, and comparisons with the geographically adjacent urban Rochester (ROC) population suggest a protective role of rural living against atopic development.…”

“…Camille Rothenberg-Lausell 1,2 Eden David 1 F I G U R E 2 Word clouds illustrate key immune and barrier-related biomarker differences between healthy Old Order Mennonite (OOM) and Rochester toddlers without (ROC) and with AD (ROC AD). Letter size indicates fold change, while color represents associated immune pathway or barrier genes, shown in the legend.…”

Human milk affects TLR4 activation and LPS-induced inflammatory cytokine expression in Caco-2 intestinal epithelial cells

“…Traditional farming lifestyle and urban lifestyle mothers in this cohort were recruited from the Old Order Mennonite (OOM) population of western New York and suburban/urban Rochester, NY, respectively. OOM mothers are known to have increased rates and duration of breastfeeding in comparison to their urban lifestyle counterparts 17 , 18 . Cryopreserved HM samples were thawed and milk fat and cells were eliminated from HM samples using differential centrifugation followed by filtration through a 0.22 μm filter.…”

Human milk affects TLR4 activation and LPS-induced cytokine expression in Caco-2 intestinal epithelial cells

“…Traditional farming lifestyle and urban lifestyle mothers in this cohort were recruited from the Old Order Mennonite (OOM) population of western New York and suburban/urban Rochester, NY, respectively. OOM mothers are known to have increased rates and duration of breastfeeding in comparison to their urban lifestyle counterparts (12,13). All participants were recruited after written informed consent.…”