Role of human milk oligosaccharide metabolizing bacteria in the development of atopic dermatitis/eczema

Abstract

Despite affecting up to 20% of infants in the United States, there is no cure for atopic dermatitis (AD), also known as eczema. Atopy usually manifests during the first six months of an infant's life and is one predictor of later allergic health problems. A diet of human milk may offer protection against developing atopic dermatitis. One milk component, human milk oligosaccharides (HMOs), plays an important role as a prebiotic in establishing the infant gut microbiome and has immunomodulatory effects on the infant immune system. The purpose of this review is to summarize the available information about bacterial members of the intestinal microbiota capable of metabolizing HMOs, the bacterial genes or metabolic products present in the intestinal tract during early life, and the relationship of these genes and metabolic products to the development of AD/eczema in infants. We find that specific HMO metabolism gene sets and the metabolites produced by HMO metabolizing bacteria may enable the protective role of human milk against the development of atopy because of interactions with the immune system. We also identify areas for additional research to further elucidate the relationship between the human milk metabolizing bacteria and atopy. Detailed metagenomic studies of the infant gut microbiota and its associated metabolomes are essential for characterizing the potential impact of human milk-feeding on the development of atopic dermatitis.

Keywords: HMO metabolizing genes; atopic dermatitis; bifidobacterium infantis; eczema; human milk oligosaccharides (HMO); infant gut microbiome; metabolome; metagenome.

Figure 1

Human milk oligosaccharides (HMOs) are the third most abundant component in human milk after lactose and lipids. Humans cannot digest HMOs. Instead, these carbohydrates are a food source for infant gut microorganisms such as B. infantis, Bacteroides spp., and others. In the gut, bacteria with HMO metabolizing genes break down complex oligosaccharides into simpler metabolites, such as short-chain fatty acids (SCFAs). These metabolites either signal the immune system through interactions with dendritic cells whose dendrites are sampling the gut lumen or by crossing the epithelial barrier to interact with immune cells in the lamina propria. Interaction between the dendritic cells and specific HMO metabolites results in dendritic cells releasing interleukins, such as IL-10, which are involved in regulating inflammation. We hypothesize that infants with microorganisms that have the complete set of HMO metabolizing genes are protected from the development of AD/eczema and/or experience reduced severity of AD/eczema. Intestinal cells and immune cells have receptors for SCFAs which are not pictured in this simplified schematic but have been reviewed by elsewhere (46). The figure was created in BioRender.com.