The Impact of Stress, Microbial Dysbiosis, and Inflammation on Necrotizing Enterocolitis

Overview

Journal Microorganisms

Specialty Microbiology

Date 2023 Sep 28

PMID 37764050

Authors

Venkata Yeramilli

Riadh Cheddadi

Heather Benjamin

Colin Martin

Affiliations

Soon will be listed here.

Abstract

Necrotizing enterocolitis (NEC) is the leading cause of intestinal morbidity and mortality in neonates. A large body of work exists; however, the pathogenesis of NEC remains poorly understood. Numerous predictors have been implicated in the development of NEC, with relatively less emphasis on maternal factors. Utilizing human tissue plays a crucial role in enhancing our comprehension of the underlying mechanisms accountable for this devastating disease. In this review, we will discuss how maternal stress affects the pathogenesis of NEC and how changes in the intestinal microbiome can influence the development of NEC. We will also discuss the results of transcriptomics-based studies and analyze the gene expression changes in NEC tissues and other molecular targets associated with the pathogenesis of NEC.

Citing Articles

Effect of gestational age on clinical features in necrotizing enterocolitis-associated intestinal perforation.

Chen M, Feng W, Hou J, Die X, Guo Z, Wang Y Front Pediatr. 2025; 12():1452207.

PMID: 39834496 PMC: 11743667. DOI: 10.3389/fped.2024.1452207.

Struggling to Understand the NEC Spectrum-Could the Integration of Metabolomics, Clinical-Laboratory Data, and Other Emerging Technologies Help Diagnosis?.

Sarafidis K, Agakidou E, Kontou A, Agakidis C, Neu J Metabolites. 2024; 14(10).

PMID: 39452903 PMC: 11509608. DOI: 10.3390/metabo14100521.

Neonatal Gut Mycobiome: Immunity, Diversity of Fungal Strains, and Individual and Non-Individual Factors.

Mpakosi A, Sokou R, Theodoraki M, Kaliouli-Antonopoulou C Life (Basel). 2024; 14(7).

PMID: 39063655 PMC: 11278438. DOI: 10.3390/life14070902.

From Mother to Infant, from Placenta to Gut: Understanding Varied Microbiome Profiles in Neonates.

Cheddadi R, Yeramilli V, Martin C Metabolites. 2023; 13(12).

PMID: 38132866 PMC: 10745069. DOI: 10.3390/metabo13121184.

References

Glorieux C, Zamocky M, Sandoval J, Verrax J, Buc Calderon P . Regulation of catalase expression in healthy and cancerous cells. Free Radic Biol Med. 2015; 87:84-97. DOI: 10.1016/j.freeradbiomed.2015.06.017. View

Gibson M, Wang B, Ahmadi S, Burnham C, Tarr P, Warner B . Developmental dynamics of the preterm infant gut microbiota and antibiotic resistome. Nat Microbiol. 2016; 1:16024. PMC: 5031140. DOI: 10.1038/nmicrobiol.2016.24. View

Chan K, Leung K, Tam Y, Lam H, Cheung H, Ma T . Genome-wide expression profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in human intestinal tissues: dysregulation of functional pathways. Ann Surg. 2013; 260(6):1128-37. DOI: 10.1097/SLA.0000000000000374. View

Warner B, Deych E, Zhou Y, Hall-Moore C, Weinstock G, Sodergren E . Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study. Lancet. 2016; 387(10031):1928-36. PMC: 5553277. DOI: 10.1016/S0140-6736(16)00081-7. View

Bailey M . Influence of stressor-induced nervous system activation on the intestinal microbiota and the importance for immunomodulation. Adv Exp Med Biol. 2014; 817:255-76. DOI: 10.1007/978-1-4939-0897-4_12. View

Sandman C, Glynn L, Dunkel Schetter C, Wadhwa P, Garite T, Chicz-DeMet A . Elevated maternal cortisol early in pregnancy predicts third trimester levels of placental corticotropin releasing hormone (CRH): priming the placental clock. Peptides. 2005; 27(6):1457-63. DOI: 10.1016/j.peptides.2005.10.002. View

Stewart C, Skeath T, Nelson A, Fernstad S, Marrs E, Perry J . Preterm gut microbiota and metabolome following discharge from intensive care. Sci Rep. 2015; 5:17141. PMC: 4657104. DOI: 10.1038/srep17141. View

Matzuk M, WAKIL S . Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science. 2001; 291(5513):2613-6. DOI: 10.1126/science.1056843. View

Hannan A . Stressing the Seminal Role of Paternal Experience in Transgenerational 'Epigenopathy' Affecting Offspring Health and Disease Susceptibility. Neuroscience. 2018; 388:472-473. DOI: 10.1016/j.neuroscience.2018.07.021. View

10.

Perez-Reytor D, Puebla C, Karahanian E, Garcia K . Use of Short-Chain Fatty Acids for the Recovery of the Intestinal Epithelial Barrier Affected by Bacterial Toxins. Front Physiol. 2021; 12:650313. PMC: 8181404. DOI: 10.3389/fphys.2021.650313. View

11.

Yang H, Yuan P, Wang L, Tache Y . Activation of the parapyramidal region in the ventral medulla stimulates gastric acid secretion through vagal pathways in rats. Neuroscience. 2000; 95(3):773-9. PMC: 8086300. DOI: 10.1016/s0306-4522(99)00490-x. View

12.

Chen G, Li Y, Su Y, Zhou L, Zhang H, Shen Q . Identification of candidate genes for necrotizing enterocolitis based on microarray data. Gene. 2018; 661:152-159. DOI: 10.1016/j.gene.2018.03.088. View

13.

Xu X, Miao Z, Sun M, Wan B . Epigenetic Mechanisms of Paternal Stress in Offspring Development and Diseases. Int J Genomics. 2021; 2021:6632719. PMC: 7837765. DOI: 10.1155/2021/6632719. View

14.

Laudadio I, Fulci V, Palone F, Stronati L, Cucchiara S, Carissimi C . Quantitative Assessment of Shotgun Metagenomics and 16S rDNA Amplicon Sequencing in the Study of Human Gut Microbiome. OMICS. 2018; 22(4):248-254. DOI: 10.1089/omi.2018.0013. View

15.

Duci M, Frigo A, Visentin S, Verlato G, Gamba P, Fascetti-Leon F . Maternal and placental risk factors associated with the development of necrotizing enterocolitis (NEC) and its severity. J Pediatr Surg. 2019; 54(10):2099-2102. DOI: 10.1016/j.jpedsurg.2019.04.018. View

16.

Gasparrini A, Wang B, Sun X, Kennedy E, Hernandez-Leyva A, Ndao I . Persistent metagenomic signatures of early-life hospitalization and antibiotic treatment in the infant gut microbiota and resistome. Nat Microbiol. 2019; 4(12):2285-2297. PMC: 6879825. DOI: 10.1038/s41564-019-0550-2. View

17.

Zijlmans M, Korpela K, Riksen-Walraven J, de Vos W, de Weerth C . Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology. 2015; 53:233-45. DOI: 10.1016/j.psyneuen.2015.01.006. View

18.

Reyna-Garfias H, Miliar A, Jarillo-Luna A, Rivera-Aguilar V, Pacheco-Yepez J, Baeza I . Repeated restraint stress increases IgA concentration in rat small intestine. Brain Behav Immun. 2009; 24(1):110-8. DOI: 10.1016/j.bbi.2009.09.005. View

19.

Afzal B, Elberson V, McLaughlin C, Kumar V . Early onset necrotizing enterocolitis (NEC) in premature twins. J Neonatal Perinatal Med. 2017; 10(1):109-112. DOI: 10.3233/NPM-1616. View

20.

Neu J, Walker W . Necrotizing enterocolitis. N Engl J Med. 2011; 364(3):255-64. PMC: 3628622. DOI: 10.1056/NEJMra1005408. View