Host Microbe Interactions in the Lactating Mammary Gland

Abstract

The bacteria present in human milk constitute the human milk microbiome (hMM). Both the older culture-based work and the more recent studies using molecular detection of bacterial DNA have reached similar conclusions: the hMM mostly consists of commensal staphylococci such as Staphylococcus epidermidis, and streptococci. The prevalence of other bacterial groups such lactobacilli varies widely, while the abundance and prevalence of bifidobacteria is generally low. Recently, the hMM became accepted as a part of a physiologically normal state with suggested potential health benefits. Most research on the hMM has focused on its composition and potential effect on the breastfed infant. A major role as a microbiome inoculum for the infant gut has been proposed, but remains to be clearly demonstrated. Herein, we also discuss the emerging connection between the hMM and mammary gland physiology and lactation. Similarities between the mammary gland and mucosal interfaces are considerable, and in particular mucosal-like immune attributes of mammary gland. The potential role of hMM-host interactions in the mammary gland in maternal health is explored with a primary focus on lactational mastitis.

Keywords: breastfeeding; human milk; lactation; mastitis; microbiome; mucosal surface.

FIGURE 1

Proposed evolution of the mammary gland from a mucus-secreting epithelial skin gland adapted from Vorbach et al. (2006). The evolutionary model postulates the divergence of specific enzymes with additional functions as discussed in the text. The original immune protective role of the skin secretion was gradually modified to a nutritive role of the contemporary mammary gland with a new specific complex secretion product called milk.

FIGURE 2

Mucosal immune features in the human mammary gland lobules. Depicted is the overall luminal interface of the mammary gland lobules and ducts where hMM cross-talk with epithelial cells occurs. Classical mucosal barrier immune features of stratification (with secretion of mucins, AMPs and IgA) and compartmentalization (with local confinement, control, and killing of bacteria) are present in breast gland and/or human milk, potentially playing a role in mother’s protection, mammary gland physiology and the hMM found under healthy conditions (left panel). Any alteration of stratification and compartmentalization could trigger transition from commensal colonization to detrimental hMM – host interactions and ultimately lead to mammary gland bacterial infection, i.e., mastitis (right panel). Altered hMM (1) may exert less bacteriostatic pressure against pathogens, (2) trigger non-specific inflammatory reaction and/or specific reaction (with immunoglobulins) against those pathogens as well as (3) epithelial cell reaction with secretion of proinflammatory mediators (cytokines, chemokines, and AMPs). Altogether, this leads to (4) attraction of additional activated immune cells by chemotaxis in the breast gland tissue and milk. The inflammation may result in breast pain, swelling, warmth, and redness characteristic to mastitis.