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      Host Microbe Interactions in the Lactating Mammary Gland

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          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.

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          Most cited references96

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          An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system.

          The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T(H)1/T(H)2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.
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            Symbiotic bacteria direct expression of an intestinal bactericidal lectin.

            The mammalian intestine harbors complex societies of beneficial bacteria that are maintained in the lumen with minimal penetration of mucosal surfaces. Microbial colonization of germ-free mice triggers epithelial expression of RegIIIgamma, a secreted C-type lectin. RegIIIgamma binds intestinal bacteria but lacks the complement recruitment domains present in other microbe-binding mammalian C-type lectins. We show that RegIIIgamma and its human counterpart, HIP/PAP, are directly antimicrobial proteins that bind their bacterial targets via interactions with peptidoglycan carbohydrate. We propose that these proteins represent an evolutionarily primitive form of lectin-mediated innate immunity, and that they reveal intestinal strategies for maintaining symbiotic host-microbial relationships.
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              Human commensals producing a novel antibiotic impair pathogen colonization.

              The vast majority of systemic bacterial infections are caused by facultative, often antibiotic-resistant, pathogens colonizing human body surfaces. Nasal carriage of Staphylococcus aureus predisposes to invasive infection, but the mechanisms that permit or interfere with pathogen colonization are largely unknown. Whereas soil microbes are known to compete by production of antibiotics, such processes have rarely been reported for human microbiota. We show that nasal Staphylococcus lugdunensis strains produce lugdunin, a novel thiazolidine-containing cyclic peptide antibiotic that prohibits colonization by S. aureus, and a rare example of a non-ribosomally synthesized bioactive compound from human-associated bacteria. Lugdunin is bactericidal against major pathogens, effective in animal models, and not prone to causing development of resistance in S. aureus. Notably, human nasal colonization by S. lugdunensis was associated with a significantly reduced S. aureus carriage rate, suggesting that lugdunin or lugdunin-producing commensal bacteria could be valuable for preventing staphylococcal infections. Moreover, human microbiota should be considered as a source for new antibiotics.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                13 August 2019
                2019
                : 10
                : 1863
                Affiliations
                [1] 1Nestlé Research, Nestlé Institute of Health Sciences , Lausanne, Switzerland
                [2] 2Nestlé Research Singapore Hub , Singapore, Singapore
                Author notes

                Edited by: Michelle (Shelley) K. McGuire, University of Idaho, United States

                Reviewed by: Alfonso Benítez-Páez, Instituto de Agroquímica y Tecnología de Alimentos (IATA), Spain; Christophe Lacroix, ETH Zürich, Switzerland

                *Correspondence: Olga Sakwinska, olga.sakwinska@ 123456rdls.nestle.com

                This article was submitted to Food Microbiology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2019.01863
                6701204
                31456777
                1fadb2a1-2e48-4473-b6df-00aebf598b3b
                Copyright © 2019 Sakwinska and Bosco.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 January 2019
                : 29 July 2019
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 150, Pages: 13, Words: 0
                Categories
                Microbiology
                Review

                Microbiology & Virology
                human milk,mucosal surface,microbiome,lactation,breastfeeding,mastitis
                Microbiology & Virology
                human milk, mucosal surface, microbiome, lactation, breastfeeding, mastitis

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