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Intestinal Dysbiosis and Necrotizing Enterocolitis: Assessment for Causality using Bradford-Hill Criteria

In recent years, several studies have shown that premature infants who develop NEC frequently display enteric dysbiosis with increased Gram-negative bacteria for several days to weeks prior to NEC onset. The importance of these findings, for the possibility of a causal role of these bacteria in NEC...

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Autores principales: Fundora, Jennifer B., Guha, Pallabi, Shores, Darla R., Pammi, Mohan, Maheshwari, Akhil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224339/
https://www.ncbi.nlm.nih.gov/pubmed/31238334
http://dx.doi.org/10.1038/s41390-019-0482-9
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author Fundora, Jennifer B.
Guha, Pallabi
Shores, Darla R.
Pammi, Mohan
Maheshwari, Akhil
author_facet Fundora, Jennifer B.
Guha, Pallabi
Shores, Darla R.
Pammi, Mohan
Maheshwari, Akhil
author_sort Fundora, Jennifer B.
collection PubMed
description In recent years, several studies have shown that premature infants who develop NEC frequently display enteric dysbiosis with increased Gram-negative bacteria for several days to weeks prior to NEC onset. The importance of these findings, for the possibility of a causal role of these bacteria in NEC pathogenesis, and for potential value of gut dysbiosis as a biomarker of NEC, is well-recognized. In this review, we present current evidence supporting the association between NEC in premature infants and enteric dysbiosis, and its evaluation using the Bradford Hill criteria for causality. To provide an objective appraisal, we developed a novel scoring system for causal inference. Despite important methodological and statistical limitations, there is support for the association from several large studies and a meta-analysis. The association draws strength from strong biological plausibility of a role of Gram-negative bacteria in NEC and from evidence for temporality, that dysbiosis may antedate NEC onset. The weakness of the association is in the low level of consistency across studies, and the lack of specificity of effect. There is a need for an improved definition of dysbiosis, either based on a critical threshold of relative abundances or at higher levels of taxonomic resolution.
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spelling pubmed-72243392020-05-14 Intestinal Dysbiosis and Necrotizing Enterocolitis: Assessment for Causality using Bradford-Hill Criteria Fundora, Jennifer B. Guha, Pallabi Shores, Darla R. Pammi, Mohan Maheshwari, Akhil Pediatr Res Article In recent years, several studies have shown that premature infants who develop NEC frequently display enteric dysbiosis with increased Gram-negative bacteria for several days to weeks prior to NEC onset. The importance of these findings, for the possibility of a causal role of these bacteria in NEC pathogenesis, and for potential value of gut dysbiosis as a biomarker of NEC, is well-recognized. In this review, we present current evidence supporting the association between NEC in premature infants and enteric dysbiosis, and its evaluation using the Bradford Hill criteria for causality. To provide an objective appraisal, we developed a novel scoring system for causal inference. Despite important methodological and statistical limitations, there is support for the association from several large studies and a meta-analysis. The association draws strength from strong biological plausibility of a role of Gram-negative bacteria in NEC and from evidence for temporality, that dysbiosis may antedate NEC onset. The weakness of the association is in the low level of consistency across studies, and the lack of specificity of effect. There is a need for an improved definition of dysbiosis, either based on a critical threshold of relative abundances or at higher levels of taxonomic resolution. 2019-06-25 2020-01 /pmc/articles/PMC7224339/ /pubmed/31238334 http://dx.doi.org/10.1038/s41390-019-0482-9 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Fundora, Jennifer B.
Guha, Pallabi
Shores, Darla R.
Pammi, Mohan
Maheshwari, Akhil
Intestinal Dysbiosis and Necrotizing Enterocolitis: Assessment for Causality using Bradford-Hill Criteria
title Intestinal Dysbiosis and Necrotizing Enterocolitis: Assessment for Causality using Bradford-Hill Criteria
title_full Intestinal Dysbiosis and Necrotizing Enterocolitis: Assessment for Causality using Bradford-Hill Criteria
title_fullStr Intestinal Dysbiosis and Necrotizing Enterocolitis: Assessment for Causality using Bradford-Hill Criteria
title_full_unstemmed Intestinal Dysbiosis and Necrotizing Enterocolitis: Assessment for Causality using Bradford-Hill Criteria
title_short Intestinal Dysbiosis and Necrotizing Enterocolitis: Assessment for Causality using Bradford-Hill Criteria
title_sort intestinal dysbiosis and necrotizing enterocolitis: assessment for causality using bradford-hill criteria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224339/
https://www.ncbi.nlm.nih.gov/pubmed/31238334
http://dx.doi.org/10.1038/s41390-019-0482-9
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