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Clostridial Strain-Specific Characteristics Associated with Necrotizing Enterocolitis.

ABSTRACT: We aimed at identifying potential bacterial factors linking clostridia with necrotizing enterocolitis (NEC). We compared the phenotypic traits, stress responses, cellular cytotoxicity, and inflammatory capabilities of the largest collection of Clostridium butyricum and Clostridium neonatale strains isolated from fecal samples of NEC preterm neonates (PN) and control PNs. When strain characteristics were used as explanatory variables, a statistical discriminant analysis allowed the separation of NEC and control strains into separate groups. Strains isolated from NEC PN were characterized by a higher viability at 30°C (P = 0.03) and higher aerotolerance (P = 0.01), suggesting that NEC strains may have a competitive and/or survival advantage in the environmental gastrointestinal tract conditions of NEC PN. Heat-treated NEC bacteria induced higher production of interleukin-8 in Caco-2 cells (P = 0.03), suggesting proinflammatory activity. In vitro, bacteria, bacterial components, and fecal filtrates showed variable cytotoxic effects affecting the cellular network and/or cell viability, without specific association with NEC or control samples. Altogether, our data support the existence of a specific clostridial strain signature associated with NEC.IMPORTANCE Clostridia are part of the commensal microbiota in preterm neonates (PN). However, microbiota analyses by culture and metagenomics have linked necrotizing enterocolitis (NEC) and intestinal colonization with clostridial species. Nevertheless, little is known about the specific characteristics that may be shared by clostridia associated with NEC compared to commensal clostridia. Therefore, our goal was to identify specific bacterial factors linking clostridial strains with NEC. We report the existence of a specific bacterial signature associated with NEC and propose that activation of the innate immune response may be a unifying causative mechanism for the development of NEC independent of a specific pathogenic organism. The present study provides new insights into NEC pathophysiology that are needed for better diagnostics and strategies for implementing prevention of the disease.

SUBMITTER: Schonherr-Hellec S

PROVIDER: S-EPMC5861827 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Clostridial Strain-Specific Characteristics Associated with Necrotizing Enterocolitis.

Schönherr-Hellec Sophia S Klein Geraldine L GL Delannoy Johanne J Ferraris Laurent L Rozé Jean Christophe JC Butel Marie José MJ Aires Julio J

Applied and environmental microbiology 20180319 7

We aimed at identifying potential bacterial factors linking clostridia with necrotizing enterocolitis (NEC). We compared the phenotypic traits, stress responses, cellular cytotoxicity, and inflammatory capabilities of the largest collection of <i>Clostridium butyricum</i> and <i>Clostridium neonatale</i> strains isolated from fecal samples of NEC preterm neonates (PN) and control PNs. When strain characteristics were used as explanatory variables, a statistical discriminant analysis allowed the ...[more]

PMID: 29352082

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Project description:ObjectiveNecrotizing enterocolitis (NEC) is associated with high morbidity and mortality among infants admitted for intensive care. The factors associated with mortality and catastrophic presentation remain poorly understood. Our objective was to describe the factors associated with mortality in infants with NEC and to quantify the degree to which catastrophic presentation contributes to mortality in infants with NEC. Catastrophic NEC was defined before data analysis as NEC that led to death within 7 days of diagnosis.Study designWe performed a retrospective review of the Pediatrix's Clinical Data Warehouse (1997 to 2009, n=560,227) to compare the demographic, therapeutic and outcome characteristics of infants who survived NEC vs those who died. Associations were tested by bivariate and multivariate analysis.ResultWe compared the 5594 infants diagnosed with NEC and who were discharged home with 1505 infants diagnosed with NEC who died. In multivariate analysis, the factors associated with death (P<0.01 in analysis) were lower estimated gestational age, lower birth weight, treatment with assisted ventilation on the day of diagnosis of NEC, treatment with vasopressors at the time of diagnosis, and Black race. Patients who received only ampicillin and gentamicin on the day of diagnosis were less likely to die. Two-thirds of NEC deaths occurred quickly (<7 days from diagnosis), with a median time of death of one day from time of diagnosis. Infants who died within 7 days of diagnosis had a higher birth weight, more often were on vasopressors and high frequency ventilation at the time of diagnosis compared with patients who died at 7 or more days. Although mortality decreased with increasing gestational age, the proportion of deaths that occurred within 7 days was relatively consistent (65 to 75% of the patients who died) across all gestational ages.ConclusionMortality among infants who have NEC remains high and infants who die of NEC commonly (66%) die quickly. Most of the factors associated with mortality are related to immaturity, low birth weight and severity of illness.

Dataset Information

Clostridial Strain-Specific Characteristics Associated with Necrotizing Enterocolitis.

Publications

Clostridial Strain-Specific Characteristics Associated with Necrotizing Enterocolitis.

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