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Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis

OBJECTIVE: Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no meth...

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Autores principales: Good, Misty, Chu, Tianjiao, Shaw, Patricia, Nolan, Lila S., Wrobleski, Joseph, Castro, Carlos, Gong, Qingqing, DeWitt, Olivia, Finegold, David N., Peters, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996588/
https://www.ncbi.nlm.nih.gov/pubmed/35410447
http://dx.doi.org/10.1186/s13148-022-01266-y
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author Good, Misty
Chu, Tianjiao
Shaw, Patricia
Nolan, Lila S.
Wrobleski, Joseph
Castro, Carlos
Gong, Qingqing
DeWitt, Olivia
Finegold, David N.
Peters, David
author_facet Good, Misty
Chu, Tianjiao
Shaw, Patricia
Nolan, Lila S.
Wrobleski, Joseph
Castro, Carlos
Gong, Qingqing
DeWitt, Olivia
Finegold, David N.
Peters, David
author_sort Good, Misty
collection PubMed
description OBJECTIVE: Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no method for early NEC detection, and the pathogenesis of NEC remains unclear. DESIGN: To further understand the molecular mechanisms that support NEC, we used solution phase hybridization and next-generation DNA sequencing of bisulfite converted DNA to perform targeted genome-wide analysis of DNA methylation at high read depth. RESULTS: We found that ileal samples from surgical NEC infants (n = 5) exist in a broadly hypermethylated state relative to their non-NEC counterparts (n = 9). These trends were not uniform, with hypermethylation being most consistently observed outside CpG islands and promoters. We further identified several biologically interesting gene promoters that displayed differential methylation in NEC and a number of biological pathways that appear dysregulated in NEC. We also found that DNA methylation patterns identified in ileal NEC tissue were correlated with those found and published previously in stool samples from NEC-affected infants. CONCLUSION: We confirmed that surgical NEC is associated with broad DNA hypermethylation in the ileum, and this may be detectable in stool samples of affected individuals. Thus, an epigenomic liquid biopsy of stool may have significant potential as a biomarker with respect to the diagnostic/predictive detection of NEC. Our findings, along with recent similar observations in colon, suggest that epigenomic dysregulation is a significant feature of surgical NEC. These findings motivate future studies which will involve the longitudinal screening of samples obtained prior to the onset of NEC. Our long-term goal is the development of novel screening, diagnostic and phenotyping methods for NEC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01266-y.
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spelling pubmed-89965882022-04-12 Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis Good, Misty Chu, Tianjiao Shaw, Patricia Nolan, Lila S. Wrobleski, Joseph Castro, Carlos Gong, Qingqing DeWitt, Olivia Finegold, David N. Peters, David Clin Epigenetics Research OBJECTIVE: Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no method for early NEC detection, and the pathogenesis of NEC remains unclear. DESIGN: To further understand the molecular mechanisms that support NEC, we used solution phase hybridization and next-generation DNA sequencing of bisulfite converted DNA to perform targeted genome-wide analysis of DNA methylation at high read depth. RESULTS: We found that ileal samples from surgical NEC infants (n = 5) exist in a broadly hypermethylated state relative to their non-NEC counterparts (n = 9). These trends were not uniform, with hypermethylation being most consistently observed outside CpG islands and promoters. We further identified several biologically interesting gene promoters that displayed differential methylation in NEC and a number of biological pathways that appear dysregulated in NEC. We also found that DNA methylation patterns identified in ileal NEC tissue were correlated with those found and published previously in stool samples from NEC-affected infants. CONCLUSION: We confirmed that surgical NEC is associated with broad DNA hypermethylation in the ileum, and this may be detectable in stool samples of affected individuals. Thus, an epigenomic liquid biopsy of stool may have significant potential as a biomarker with respect to the diagnostic/predictive detection of NEC. Our findings, along with recent similar observations in colon, suggest that epigenomic dysregulation is a significant feature of surgical NEC. These findings motivate future studies which will involve the longitudinal screening of samples obtained prior to the onset of NEC. Our long-term goal is the development of novel screening, diagnostic and phenotyping methods for NEC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01266-y. BioMed Central 2022-04-11 /pmc/articles/PMC8996588/ /pubmed/35410447 http://dx.doi.org/10.1186/s13148-022-01266-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Good, Misty
Chu, Tianjiao
Shaw, Patricia
Nolan, Lila S.
Wrobleski, Joseph
Castro, Carlos
Gong, Qingqing
DeWitt, Olivia
Finegold, David N.
Peters, David
Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis
title Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis
title_full Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis
title_fullStr Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis
title_full_unstemmed Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis
title_short Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis
title_sort selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996588/
https://www.ncbi.nlm.nih.gov/pubmed/35410447
http://dx.doi.org/10.1186/s13148-022-01266-y
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