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      Current and future methods of probiotic therapy for necrotizing enterocolitis

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          Abstract

          Necrotizing enterocolitis (NEC) is a complex intestinal disease that primarily affects premature neonates. Given its significant mortality and morbidity, there is an urgent need to develop improved prophylactic measures against the disease. One potential preventative strategy for NEC is the use of probiotics. Although there has been significant interest for decades in probiotics in neonatal care, no clear guidelines exist regarding which probiotic to use or for which patients, and no FDA-approved products exist on the market for NEC. In addition, there is lack of agreement regarding the benefits of probiotics in neonates, as well as some concerns about the safety and efficacy of available products. We discuss currently available probiotics as well as next-generation probiotics and novel delivery strategies which may offer an avenue to capitalize on the benefits of probiotics, while minimizing the risks. Thus, probiotics may still prove to be an effective prevention strategy for NEC, although further product development and research is needed to support use in the preterm population.

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          Most cited references112

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          Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic.

          An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.
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            Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics

            With the continued interest in the role of the gut microbiota in health, attention has now turned to how to harness the microbiota for the benefit of the host. This Consensus Statement outlines the definition and scope of the term 'prebiotic' as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in December 2016.
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              Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns.

              Upon delivery, the neonate is exposed for the first time to a wide array of microbes from a variety of sources, including maternal bacteria. Although prior studies have suggested that delivery mode shapes the microbiota's establishment and, subsequently, its role in child health, most researchers have focused on specific bacterial taxa or on a single body habitat, the gut. Thus, the initiation stage of human microbiome development remains obscure. The goal of the present study was to obtain a community-wide perspective on the influence of delivery mode and body habitat on the neonate's first microbiota. We used multiplexed 16S rRNA gene pyrosequencing to characterize bacterial communities from mothers and their newborn babies, four born vaginally and six born via Cesarean section. Mothers' skin, oral mucosa, and vagina were sampled 1 h before delivery, and neonates' skin, oral mucosa, and nasopharyngeal aspirate were sampled <5 min, and meconium <24 h, after delivery. We found that in direct contrast to the highly differentiated communities of their mothers, neonates harbored bacterial communities that were undifferentiated across multiple body habitats, regardless of delivery mode. Our results also show that vaginally delivered infants acquired bacterial communities resembling their own mother's vaginal microbiota, dominated by Lactobacillus, Prevotella, or Sneathia spp., and C-section infants harbored bacterial communities similar to those found on the skin surface, dominated by Staphylococcus, Corynebacterium, and Propionibacterium spp. These findings establish an important baseline for studies tracking the human microbiome's successional development in different body habitats following different delivery modes, and their associated effects on infant health.
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                Author and article information

                Contributors
                Journal
                Front Pediatr
                Front Pediatr
                Front. Pediatr.
                Frontiers in Pediatrics
                Frontiers Media S.A.
                2296-2360
                02 March 2023
                2023
                : 11
                : 1120459
                Affiliations
                Department of Pediatric Surgery, Center for Perinatal Research, Nationwide Children’s Hospital , Columbus, OH, United States
                Author notes

                Edited by: Minesh Khashu, University Hospitals Dorset NHS Foundation Trust, United Kingdom

                Reviewed by: Dhirendra Kumar Singh, University of North Carolina at Chapel Hill, United States Ozge Aydemir, Eskişehir Osmangazi University, Turkey

                [* ] Correspondence: Gail E. Besner gail.besner@ 123456nationwidechildrens.org

                Specialty Section: This article was submitted to Neonatology, a section of the journal Frontiers in Pediatrics

                Article
                10.3389/fped.2023.1120459
                10017871
                36937955
                be0181e2-c8b1-400d-a74c-878961a83775
                © 2023 Sajankila, Wala, Ragan, Volpe, Dumbauld, Purayil, Mihi and Besner.

                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
                : 10 December 2022
                : 31 January 2023
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 131, Pages: 0, Words: 0
                Funding
                Funded by: NIH, doi 10.13039/100000002;
                Award ID: R01 GM1123482
                Funded by: NIH, doi 10.13039/100000002;
                Award ID: R42 DK107168
                Funded by: NIH, doi 10.13039/100000002;
                Award ID: T32 AI106704
                Funded by: Ohio State University, doi 10.13039/100006928;
                Award ID:  
                Funded by: The Research Institute at Nationwide Children’s Hospital, doi 10.13039/100011500;
                Award ID:  
                Funded by: Department of Surgery, Nationwide Children’s Hospital, doi 10.13039/100007520;
                Award ID:  
                This work was funded by NIH R01 GM1123482 (GB), NIH R42 GM122130 (GB), NIH T32 AI106704 (Advanced Research Training in Immunology for Surgery Trainees) through Ohio State University (NS), The Research Institute at Nationwide Children's Hospital (GB), and the Department of Surgery, Nationwide Children's Hospital (GB).
                Categories
                Pediatrics
                Review

                necrotizing enterocolitis,nec,probiotic,intestine,gut,microbiome,dysbiosis

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