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      Human Milk’s Hidden Gift: Implications of the Milk Microbiome for Preterm Infants’ Health

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          Abstract

          Breastfeeding is considered the gold standard for infants’ nutrition, as mother’s own milk (MOM) provides nutritional and bioactive factors functional to optimal development. Early life microbiome is one of the main contributors to short and long-term infant health status, with the gut microbiota (GM) being the most studied ecosystem. Some human milk (HM) bioactive factors, such as HM prebiotic carbohydrates that select for beneficial bacteria, and the specific human milk microbiota (HMM) are emerging as early mediators in the relationship between the development of GM in early life and clinical outcomes. The beneficial role of HM becomes even more crucial for preterm infants, who are exposed to significant risks of severe infection in early life as well as to adverse short and long-term outcomes. When MOM is unavailable or insufficient, donor human milk (DHM) constitutes the optimal nutritional choice. However, little is known about the specific effect of DHM on preterm GM and its potential functional implication on HMM. The purpose of this narrative review is to summarize recent findings on HMM origin and composition and discuss the role of HMM on infant health and development, with a specific focus on preterm infants.

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          Most cited references49

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          Human milk is a source of lactic acid bacteria for the infant gut.

          To investigate whether human breast milk contains potentially probiotic lactic acid bacteria, and therefore, whether it can be considered a synbiotic food. Study design Lactic acid bacteria were isolated from milk, mammary areola, and breast skin of eight healthy mothers and oral swabs and feces of their respective breast-fed infants. Some isolates (178 from each mother and newborn pair) were randomly selected and submitted to randomly amplified polymorphic DNA (RAPD) polymerase chain reaction analysis, and those that displayed identical RAPD patterns were identified by 16S rDNA sequencing. Within each mother and newborn pair, some rod-shaped lactic acid bacteria isolated from mammary areola, breast milk, and infant oral swabs and feces displayed identical RAPD profiles. All of them, independently from the mother and child pair, were identified as Lactobacillus gasseri. Similarly, among coccoid lactic acid bacteria from these different sources, some shared an identical RAPD pattern and were identified as Enterococcus faecium. In contrast, none of the lactic acid bacteria isolated from breast skin shared RAPD profiles with lactic acid bacteria of the other sources. Breast-feeding can be a significant source of lactic acid bacteria to the infant gut. Lactic acid bacteria present in milk may have an endogenous origin and may not be the result of contamination from the surrounding breast skin.
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            Studying Vertical Microbiome Transmission from Mothers to Infants by Strain-Level Metagenomic Profiling

            Early infant exposure is important in the acquisition and ultimate development of a healthy infant microbiome. There is increasing support for the idea that the maternal microbial reservoir is a key route of microbial transmission, and yet much is inferred from the observation of shared species in mother and infant. The presence of common species, per se, does not necessarily equate to vertical transmission, as species exhibit considerable strain heterogeneity. It is therefore imperative to assess whether shared microbes belong to the same genetic variant (i.e., strain) to support the hypothesis of vertical transmission. Here we demonstrate the potential of shotgun metagenomics and strain-level profiling to identify vertical transmission events. Combining these data with metatranscriptomics, we show that it is possible not only to identify and track the fate of microbes in the early infant microbiome but also to investigate the actively transcribing members of the community. These approaches will ultimately provide important insights into the acquisition, development, and community dynamics of the infant microbiome.
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              Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors

              Breastmilk contains a complex community of bacteria that may help seed the infant gut microbiota. The composition and determinants of milk microbiota are poorly understood. Among 393 mother-infant dyads from the CHILD cohort, we found that milk microbiota at 3-4 months postpartum was dominated by inversely correlated Proteobacteria and Firmicutes, and exhibited discrete compositional patterns. Milk microbiota composition and diversity were associated with maternal factors (BMI, parity, and mode of delivery), breastfeeding practices, and other milk components in a sex-specific manner. Causal modeling identified mode of breastfeeding as a key determinant of milk microbiota composition. Specifically, providing pumped breastmilk was consistently associated with multiple microbiota parameters including enrichment of potential pathogens and depletion of bifidobacteria. Further, these data support the retrograde inoculation hypothesis, whereby the infant oral cavity impacts the milk microbiota. Collectively, these results identify features and determinants of human milk microbiota composition, with potential implications for infant health and development.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                04 December 2019
                December 2019
                : 11
                : 12
                : 2944
                Affiliations
                [1 ]Neonatal Intensive Care Unit, AOU Bologna, Department of Medical and Surgical Sciences (DIMEC), University of Bologna. via Massarenti, 11-40138 Bologna, Italy; i.beghetti@ 123456gmail.com (I.B.); silvia.martini4@ 123456gmail.com (S.M.); luigi.corvaglia@ 123456unibo.it (L.C.)
                [2 ]Unit of Molecular Ecology of Health, Department of Pharmacy and Biotechnology (FABIT), University of Bologna. Via Belmeloro, 6–40126 Bologna, Italy; elena.biagi@ 123456unibo.it (E.B.); patrizia.brigidi@ 123456unibo.it (P.B.)
                Author notes
                [* ]Correspondence: arianna.aceti2@ 123456unibo.it ; Tel./Fax: +0039-(0)51-342-754
                Author information
                https://orcid.org/0000-0003-4819-1830
                https://orcid.org/0000-0003-2078-7114
                https://orcid.org/0000-0001-9274-985X
                Article
                nutrients-11-02944
                10.3390/nu11122944
                6950588
                31817057
                1003796e-47b7-4c01-a670-1f9a9a05775e
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 September 2019
                : 09 November 2019
                Categories
                Review

                Nutrition & Dietetics
                human milk microbiota,preterm infants,breastfeeding,donor human milk
                Nutrition & Dietetics
                human milk microbiota, preterm infants, breastfeeding, donor human milk

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