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Biomarkers of gut injury in neonates - where are we in predicting necrotising enterocolitis?

ABSTRACT: Despite advances in neonatal care Necrotising Enterocolitis (NEC) continues to have a significant mortality and morbidity rate, and with increasing survival of those more immature infants the population at risk of NEC is increasing. Ischaemia, reperfusion, and inflammation underpin diseases affecting intestinal blood flow causing gut injury including Necrotising Enterocolitis. There is increasing interest in tissue biomarkers of gut injury in neonates, particularly those representing changes in intestinal wall barrier and permeability, to determine whether these could be useful biomarkers of gut injury. This article reviews current and newly proposed markers of gut injury, the available literature evidence, recent advances and considers how effective they are in clinical practice. We discuss each biomarker in terms of its effectiveness in predicting NEC onset and diagnosis or predicting NEC severity and then those that will aid in surveillance and identifying those infants are greatest risk of developing NEC.

SUBMITTER: Howarth C

PROVIDER: S-EPMC9742605 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Biomarkers of gut injury in neonates - where are we in predicting necrotising enterocolitis?

Howarth Claire C Banerjee Jayanta J Eaton Simon S Aladangady Narendra N

Frontiers in pediatrics 20221128

Despite advances in neonatal care Necrotising Enterocolitis (NEC) continues to have a significant mortality and morbidity rate, and with increasing survival of those more immature infants the population at risk of NEC is increasing. Ischaemia, reperfusion, and inflammation underpin diseases affecting intestinal blood flow causing gut injury including Necrotising Enterocolitis. There is increasing interest in tissue biomarkers of gut injury in neonates, particularly those representing changes in ...[more]

PMID: 36518779

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Project description:BackgroundGut bacteria might predispose to or protect from necrotising enterocolitis, a severe illness linked to prematurity. In this observational prospective study we aimed to assess whether one or more bacterial taxa in the gut differ between infants who subsequently develop necrotising enterocolitis (cases) and those who do not (controls).MethodsWe enrolled very low birthweight (1500 g and lower) infants in the primary cohort (St Louis Children's Hospital) between July 7, 2009, and Sept 16, 2013, and in the secondary cohorts (Kosair Children's Hospital and Children's Hospital at Oklahoma University) between Sept 12, 2011 and May 25, 2013. We prospectively collected and then froze stool samples for all infants. Cases were defined as infants whose clinical courses were consistent with necrotising enterocolitis and whose radiographs fulfilled criteria for Bell's stage 2 or 3 necrotising enterocolitis. Control infants (one to four per case; not fixed ratios) with similar gestational ages, birthweight, and birth dates were selected from the population after cases were identified. Using primers specific for bacterial 16S rRNA genes, we amplified and then pyrosequenced faecal DNA from stool samples. With use of Dirichlet multinomial analysis and mixed models to account for repeated measures, we identified host factors, including development of necrotising enterocolitis, associated with gut bacterial populations.FindingsWe studied 2492 stool samples from 122 infants in the primary cohort, of whom 28 developed necrotising enterocolitis; 94 infants were used as controls. The microbial community structure in case stools differed significantly from those in control stools. These differences emerged only after the first month of age. In mixed models, the time-by-necrotising-enterocolitis interaction was positively associated with Gammaproteobacteria (p=0·0010) and negatively associated with strictly anaerobic bacteria, especially Negativicutes (p=0·0019). We studied 1094 stool samples from 44 infants in the secondary cohorts. 18 infants developed necrotising enterocolitis (cases) and 26 were controls. After combining data from all cohorts (166 infants, 3586 stools, 46 cases of necrotising enterocolitis), there were increased proportions of Gammaproteobacteria (p=0·0011) and lower proportions of both Negativicutes (p=0·0013) and the combined Clostridia-Negativicutes class (p=0·0051) in infants who went on to develop necrotising enterocolitis compared with controls. These associations were strongest in both the primary cohort and the overall cohort for infants born at less than 27 weeks' gestation.InterpretationA relative abundance of Gammaproteobacteria (ie, Gram-negative facultative bacilli) and relative paucity of strict anaerobic bacteria (especially Negativicutes) precede necrotising enterocolitis in very low birthweight infants. These data offer candidate targets for interventions to prevent necrotising enterocolitis, at least among infants born at less than 27 weeks' gestation.FundingNational Institutes of Health (NIH), Foundation for the NIH, the Children's Discovery Institute.

Project description:BackgroundDysbacteriosis is thought to play an important role in the pathogenesis of necrotizing enterocolitis (NEC). We aimed to identify new biomarkers among gut microbiota and short-chain fatty acids (SCFAs) for the early prediction of NEC.Materials and methodsThirty-four preterm infants with gestational ages of ≤ 34 weeks who developed gastrointestinal symptoms were divided into the NEC group (n = 17) and non-NEC group (n = 17). In the NEC group, the gut microbiota and SCFAs in feces were assessed when the infants were enrolled (Group P) and when they were diagnosed with NEC (Group N). In the non-NEC group, samples were assessed when the infants were enrolled (Group C).ResultsThe Ace and Chao1 indices were higher in Group P than in Group C (P < 0.05), and there was no difference between Groups C and N or between Groups P and N (P > 0.05). There was no significant difference in the Simpson and Shannon indices among Groups C, P and N (P > 0.05). The four main phyla showed no differences (P > 0.05) in composition, while at the genus level, compared with Group C, in Group P, Clostridioides, Blautia and Clostridium_sensu_stricto_1 were increased, while Lactobacillus and Bifidobacterium were decreased (P < 0.05). At the species level, Streptococcus salivarius and Rothia mucilaginosa increased, while Bifidobacterium animals subsp. lactis decreased (P < 0.05). In Group N, at the genus level, Stenotrophomonas, Streptococcus and Prevotella increased (P < 0.05). Compared with those in Group C, the levels of acetic acid, propanoic acid and butyric acid decreased significantly in Groups P and N (P < 0.05), and the areas under the curves (AUCs) of these three SCFAs between groups C and P were 0.73, 0.70, and 0.68, respectively.ConclusionThe increase in Streptococcus salivarius and Rothia mucilaginosa and decrease in Bifidobacterium_animals_subsp._lactis, as well as the decrease in acetic, propionic and butyric acids, may help in the early prediction of NEC.

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Biomarkers of gut injury in neonates - where are we in predicting necrotising enterocolitis?

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Biomarkers of gut injury in neonates - where are we in predicting necrotising enterocolitis?

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