Abstract

The mechanism underlying the allergy-protective effects of raw cow’s milk is still unknown, but the modulation of the gut microbiome may play a role. The effects of consuming raw cow’s milk or processed milk on fecal microbial communities were therefore characterized in an experimental murine model. C3H/HeOuJ mice were treated with raw milk, pasteurized milk, skimmed raw milk, pasteurized milk supplemented with alkaline phosphatase (ALP), or phosphate-buffered saline (PBS) for eight days prior to sensitization and challenge with ovalbumin (OVA). Fecal samples were collected after milk exposure and after OVA sensitization, and microbiomes were characterized using 16S ribosomal RNA gene amplicon sequencing. Treatment with raw milk prior to OVA sensitization increased the relative abundance of putative butyrate-producing bacteria from the taxa Lachnospiraceae UCG-001, Lachnospiraceae UCG-008, and Ruminiclostridium 5 (Clostridial clusters XIVa and IV), while it decreased the relative abundance of Proteobacterial genera such as Parasutterella, a putative pro-inflammatory bacterial genus. This effect was observed after eight days of raw milk exposure and became more pronounced five weeks later, after allergic sensitization in the absence of milk. Similar trends were observed after treatment with skimmed raw milk. Conversely, the feeding of pasteurized milk led to a loss of allergy protection and a putative dysbiotic microbiome. The addition of ALP to pasteurized milk restored the protective effect observed with raw milk and mitigated some of the microbial community alterations associated with milk pasteurization. Raw milk-induced protection against food allergic symptoms in mice is accompanied by an increased relative abundance of putative butyrate-producing Clostridiales and a decreased relative abundance of putative pro-inflammatory Proteobacteria. Given the safety concerns regarding raw milk consumption, this knowledge is key for the development of new, microbiologically safe, preventive strategies to reduce the incidence of allergic diseases.

Highlights

  • The prevalence of allergic diseases such as allergic rhinitis, atopic dermatitis, asthma, and food allergy has increased dramatically in recent decades and has become a major health problem, in affluent and fast-developing societies [1]

  • We showed that alkaline phosphatase (ALP), a heat-sensitive bioactive raw milk component, was able to partially

  • Parasutterella were identified by using a taxon-by-taxon Kruskal–Wallis test, while Bifidobacterium were not significant (FDR-p = 0.162; Supplementary Materials Table S2) by this analysis

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Summary

Introduction

The prevalence of allergic diseases such as allergic rhinitis, atopic dermatitis, asthma, and food allergy has increased dramatically in recent decades and has become a major health problem, in affluent and fast-developing societies [1]. A well-known example is the “farm effect” wherein children growing up on a farm have a lower risk of developing allergic diseases compared to children who are raised in the same rural area but not on a farm [9,10,11,12,13]. This beneficial “farm effect” has been mainly attributed to the consumption of raw, unprocessed cow’s milk [14,15,16,17,18,19]. Since the allergyprotective raw milk effect has been observed in children not exposed to a farming environment [14,15,16], raw cow’s milk consumption could provide a potential natural solution for allergic diseases

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