Abstract

BackgroundIn addition to farming exposures in childhood, maternal farming exposures provide strong protection against allergic disease in their children; however, the effect of farming lifestyle on human milk (HM) composition is unknown.ObjectiveThis study aims to characterize the maternal immune effects of Old Order Mennonite (OOM) traditional farming lifestyle when compared with Rochester (ROC) families at higher risk for asthma and allergic diseases using HM as a proxy.MethodsHM samples collected at median 2 months of lactation from 52 OOM and 29 ROC mothers were assayed for IgA1 and IgA2 antibodies, cytokines, endotoxin, HM oligosaccharides (HMOs), and targeted fatty acid (FA) metabolites. Development of early childhood atopic diseases in children by 3 years of age was assessed. In addition to group comparisons, systems level network analysis was performed to identify communities of multiple HM factors in ROC and OOM lifestyle.ResultsHM contains IgA1 and IgA2 antibodies broadly recognizing food, inhalant, and bacterial antigens. OOM HM has significantly higher levels of IgA to peanut, ovalbumin, dust mites, and Streptococcus equii as well TGF-β2, and IFN-λ3. A strong correlation occurred between maternal antibiotic use and levels of several HMOs. Path-based analysis of HMOs shows lower activity in the path involving lactoneohexaose (LNH) in the OOM as well as higher levels of lacto-N-neotetraose (LNnT) and two long-chain FAs C-18OH (stearic acid) and C-23OH (tricosanoic acid) compared with Rochester HM. OOM and Rochester milk formed five different clusters, e.g., butyrate production was associated with Prevotellaceae, Veillonellaceae, and Micrococcaceae cluster. Development of atopic disease in early childhood was more common in Rochester and associated with lower levels of total IgA, IgA2 to dust mite, as well as of TSLP.ConclusionTraditional, agrarian lifestyle, and antibiotic use are strong regulators of maternally derived immune and metabolic factors, which may have downstream implications for postnatal developmental programming of infant’s gut microbiome and immune system.

Highlights

  • Asthma and atopic diseases including food allergy, eczema, and rhinoconjunctivitis have increased exponentially over recent decades of industrialization and urbanization and are the most common chronic medical conditions affecting children in the USA and are a global public health concern [1]

  • Using human samples and infant cohorts, we have shown that human milk IgA controls excessive intestinal uptake of food antigens, which is associated with protection against food allergies in the offspring [21], as are higher levels of Transforming growth factor (TGF)-b1, along with IL-10 and IL-6 [22]

  • We show that Old Order Mennonites (OOM) milk is more abundant in many immune components, especially those involved in IgA immunity, and LNnT which enhances Bifidobacterium enrichment

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Summary

Introduction

Asthma and atopic diseases including food allergy, eczema, and rhinoconjunctivitis have increased exponentially over recent decades of industrialization and urbanization and are the most common chronic medical conditions affecting children in the USA and are a global public health concern [1]. Maternal microbial exposures during pregnancy have a strong and independent protective impact on atopic sensitization and allergic disease in their children [2,3,4, 12] This protection was associated with maternal exposure to farm animals and unboiled farm milk [3, 10], increased T regulatory cells (Tregs) in cord blood [13], and altered expression of receptors of the innate immunity (TLR2, TLR4, CD14) in school-aged children [3]. These data suggest a maternal farmlife effect on protection against allergic diseases, but to date, only a single study has assessed the maternal, postnatal farming lifestyle effect related to human milk composition. In addition to farming exposures in childhood, maternal farming exposures provide strong protection against allergic disease in their children; the effect of farming lifestyle on human milk (HM) composition is unknown

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