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      Changes of intestinal microflora in neonatal necrotizing enterocolitis: a single-center study

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          Abstract

          Objective

          To investigate the changes in the diversity and dynamics of intestinal microflora in patients with neonatal necrotizing enterocolitis (NEC) in a single center in China.

          Methods

          In this prospective study conducted between 2016 and 2019, feces were collected from 28 neonates with NEC and 30 control neonates to analyze the species richness and Shannon’s diversity index of the bands, which were also sequenced via PCR-denaturing gradient gel electrophoresis.

          Results

          The species richness and Shannon’s diversity index were significantly lower in the NEC group than in the control group, indicating that the diversity of intestinal flora was reduced in NEC. The numbers of samples positive for Bacteroides and Klebsiella were higher in the NEC group, whereas Escherichia coli, Bifidobacterium, and Lactobacillus were less frequently detected in patients with NEC than in controls. The prevalence of intestinal bacteria normalized after the resolution of NEC.

          Conclusion

          The decrease of intestinal flora diversity in neonates with NEC, especially the decreased prevalence of probiotic bacteria, may be an important factor in the pathogenesis of NEC.

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          Most cited references12

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          Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants

          Background Necrotizing enterocolitis (NEC) is a devastating intestinal disease that afflicts 10% of extremely preterm infants. The contribution of early intestinal colonization to NEC onset is not understood, and predictive biomarkers to guide prevention are lacking. We analyzed banked stool and urine samples collected prior to disease onset from infants 99% versus 99% versus 38% in the other NEC cases and 84% in controls, P = 0.01). NEC preceded by Firmicutes dysbiosis occurred earlier (onset, days 7 to 21) than NEC preceded by Proteobacteria dysbiosis (onset, days 19 to 39). All NEC cases lacked Propionibacterium and were preceded by either Firmicutes (≥98% relative abundance, days 4 to 9) or Proteobacteria (≥90% relative abundance, days 10 to 16) dysbiosis, while only 25% of controls had this phenotype (predictive value 88%, P = 0.001). Analysis of days 4 to 9 urine samples found no metabolites associated with all NEC cases, but alanine was positively associated with NEC cases that were preceded by Firmicutes dysbiosis (P < 0.001) and histidine was inversely associated with NEC cases preceded by Proteobacteria dysbiosis (P = 0.013). A high urinary alanine:histidine ratio was associated with microbial characteristics (P < 0.001) and provided good prediction of overall NEC (predictive value 78%, P = 0.007). Conclusions Early dysbiosis is strongly involved in the pathobiology of NEC. These striking findings require validation in larger studies but indicate that early microbial and metabolomic signatures may provide highly predictive biomarkers of NEC.
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            Gut bacteria are rarely shared by co-hospitalized premature infants, regardless of necrotizing enterocolitis development

            Premature infants are highly vulnerable to aberrant gastrointestinal tract colonization, a process that may lead to diseases like necrotizing enterocolitis. Thus, spread of potential pathogens among hospitalized infants is of great concern. Here, we reconstructed hundreds of high-quality genomes of microorganisms that colonized co-hospitalized premature infants, assessed their metabolic potential, and tracked them over time to evaluate bacterial strain dispersal among infants. We compared microbial communities in infants who did and did not develop necrotizing enterocolitis. Surprisingly, while potentially pathogenic bacteria of the same species colonized many infants, our genome-resolved analysis revealed that strains colonizing each baby were typically distinct. In particular, no strain was common to all infants who developed necrotizing enterocolitis. The paucity of shared gut colonizers suggests the existence of significant barriers to the spread of bacteria among infants. Importantly, we demonstrate that strain-resolved comprehensive community analysis can be accomplished on potentially medically relevant time scales. DOI: http://dx.doi.org/10.7554/eLife.05477.001
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              Prevention of Necrotizing Enterocolitis Through Manipulation of the Intestinal Microbiota of the Premature Infant.

              In spite of four decades of research, necrotizing enterocolitis (NEC) remains the most common gastrointestinal complication in premature infants with high mortality and long-term morbidity. The composition of the intestinal microbiota of the premature infant differs dramatically from that of the healthy term infant and appears to be an important risk factor for NEC.
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                Author and article information

                Journal
                J Int Med Res
                J. Int. Med. Res
                IMR
                spimr
                The Journal of International Medical Research
                SAGE Publications (Sage UK: London, England )
                0300-0605
                1473-2300
                24 September 2020
                September 2020
                : 48
                : 9
                : 0300060520957804
                Affiliations
                [1 ]Department of Neonate, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou Province, China
                [2 ]Department of Emergency, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou Province, China
                [3 ]Drug Clinical Trial Institution, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou Province, China
                Author notes
                [*]Nanqu Huang, Drug Clinical Trial Institution, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou Province 563000, China. Email: huangnanqu@ 123456163.com
                Author information
                https://orcid.org/0000-0001-9697-8406
                https://orcid.org/0000-0002-1910-6660
                Article
                10.1177_0300060520957804
                10.1177/0300060520957804
                7520936
                32967507
                0c78abdd-fe21-4cb0-a8b3-8de5643c7bdc
                © The Author(s) 2020

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 26 May 2020
                : 20 August 2020
                Funding
                Funded by: Zunyi City Innovative Talent Team Training Project;
                Award ID: 2019-3
                Funded by: Excellent Young Technological Innovation Talent Training Project of Zunyi;
                Award ID: 2018-10
                Funded by: Joint Technology R&D Project of Zunyi;
                Award ID: 2017-39, 2018-190, 2020-12
                Categories
                Prospective Clinical Research Report
                Custom metadata
                ts2

                neonatal necrotizing enterocolitis,pediatrics,intestinal microflora,probiotics,bacterial diversity,species richness,feces

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