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      Strategies for the Preservation, Restoration and Modulation of the Human Milk Microbiota. Implications for Human Milk Banks and Neonatal Intensive Care Units

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          Abstract

          Studies carried in the last years have revealed that human milk contains a site-specific microbiota and constitutes a source of potentially beneficial bacteria to the infant gut. Once in the infant gut, these bacteria contribute to the assembly of a physiological gut microbiota and may play several functions, contributing to infant metabolism, protection against infections, immunomodulation or neuromodulation. Many preterm neonates are fed with pasteurized donor’s human milk (DHM) or formula and, therefore, are devoid of contact with human milk microbes. As a consequence, new strategies are required to allow the exposition of a higher number of preterm infants to the human milk microbiota early in life. The first strategy would be to promote and to increase the use of own mother’s milk (OMM) in Neonatal Intensive Care Units (NICUs). Even small quantities of OMM can be very valuable since they would be added to DHM in order to microbiologically “customize” it. When OMM is not available, a better screening of donor women, including routine cytomegalovirus (CMV) screening of milk, may help to avoid the pasteurization of the milk provided by, at least, a relevant proportion of donors. Finally, when pasteurized DHM or formula are the only feeding option, their supplementation with probiotic bacteria isolated from human milk, such as lactic acid bacteria or bifidobacteria, may be an alternative to try to restore a human milk-like microbiota before feeding the babies. In the future, the design of human milk bacterial consortia (minimal human milk microbiotas), including well characterized strains representative of a healthy human milk microbiota, may be an attractive strategy to provide a complex mix of strains specifically tailored to this target population.

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          Most cited references140

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          Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection.

          Clostridium difficile infection (CDI) is a gastrointestinal disease believed to be causally related to perturbations to the intestinal microbiota. When standard treatment has failed, intestinal microbiota transplantation (IMT) is an alternative therapy for patients with CDI. IMT involves infusing intestinal microorganisms (in a suspension of healthy donor stool) into the intestine of a sick patient to restore the microbiota. However, protocols and reported efficacy for IMT vary. We conducted a systematic literature review of IMT treatment for recurrent CDI and pseudomembranous colitis. In 317 patients treated across 27 case series and reports, IMT was highly effective, showing disease resolution in 92% of cases. Effectiveness varied by route of instillation, relationship to stool donor, volume of IMT given, and treatment before infusion. Death and adverse events were uncommon. These findings can guide physicians interested in implementing the procedure until better designed studies are conducted to confirm best practices.
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            Shifting the balance: antibiotic effects on host-microbiota mutualism.

            Antibiotics have been used effectively as a means to treat bacterial infections in humans and animals for over half a century. However, through their use, lasting alterations are being made to a mutualistic relationship that has taken millennia to evolve: the relationship between the host and its microbiota. Host-microbiota interactions are dynamic; therefore, changes in the microbiota as a consequence of antibiotic treatment can result in the dysregulation of host immune homeostasis and an increased susceptibility to disease. A better understanding of both the changes in the microbiota as a result of antibiotic treatment and the consequential changes in host immune homeostasis is imperative, so that these effects can be mitigated.
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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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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                09 November 2018
                2018
                : 9
                : 2676
                Affiliations
                [1] 1Department of Galenic Pharmacy and Food Technology, Complutense University of Madrid , Madrid, Spain
                [2] 2Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias – Consejo Superior de Investigaciones Científicas , Villaviciosa, Spain
                [3] 3Department of Nutrition and Food Science, Complutense University of Madrid , Madrid, Spain
                Author notes

                Edited by: Paloma López, Centro de Investigaciones Biológicas (CIB), Spain

                Reviewed by: Sertac Arslanoglu, Istanbul Medeniyet University, Turkey; Teresa Requena, Consejo Superior de Investigaciones Científicas (CSIC), Spain

                *Correspondence: Juan M. Rodríguez, jmrodrig@ 123456vet.ucm.es

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

                Article
                10.3389/fmicb.2018.02676
                6237971
                76ee811a-f3d5-4918-9e17-37dd63f69f1f
                Copyright © 2018 Fernández, Ruiz, Jara, Orgaz and Rodríguez.

                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
                : 17 July 2018
                : 19 October 2018
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 195, Pages: 13, Words: 0
                Funding
                Funded by: Ministerio de Economía y Competitividad 10.13039/501100003329
                Categories
                Microbiology
                Review

                Microbiology & Virology
                human milk,microbiota,probiotics,lactic acid bacteria,minimal microbiota,preterm infants,nicu,human milk bank

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