Role of Clostridium Perfringens in Neonatal Necrotizing Enterocolitis and the Utility of Anaerobic Blood Cultures

Introduction: Clostridium perfringens is a gram-positive anaerobic bacillus that causes various clinical diseases, including necrotizing enterocolitis in newborns. The progression could be fulminant and lethal. Presentation of the cases: We report 3 cases of necrotizing enterocolitis due to C. perfringens from 2 high-complexity public centers in Chile. Conclusion: Strong clinical suspicion combined with early microbiological identification may modify patient evolution. Anaerobic blood cultures have become a fundamental diagnostic method; therefore, having this tool in neonatal units would be useful

Enteric Nervous System in Neonatal Necrotizing Enterocolitis

Background: The pathophysiology of necrotizing enterocolitis (NEC) is not clear, but increasing information suggests that the risk and severity of NEC may be influenced by abnormalities in the enteric nervous system (ENS). Objective: The purpose of this review was to scope and examine the research related to ENS-associated abnormalities that have either been identified in NEC or have been noted in other inflammatory bowel disorders (IBDs) with histopathological abnormalities similar to NEC. The aim was to summarize the research findings, identify research gaps in existing literature, and disseminate them to key knowledge end-users to collaborate and address the same in future studies. Methods: Articles that met the objectives of the study were identified through an extensive literature search in the databases PubMed, EMBASE, and Scopus. Results : The sources identified through the literature search revealed that: (1) ENS may be involved in NEC development and post-NEC complications, (2) NEC development is associated with changes in the ENS, and (3) NEC-associated changes could be modulated by the ENS. Conclusions: The findings from this review identify the enteric nervous as a target in the development and progression of NEC. Thus, factors that can protect the ENS can potentially prevent, and treat NEC and post-NEC complications. This review serves to summarize the existing literature and highlights a need for further research on the involvement of ENS in NEC.

Hypoxia: The “Invisible Pusher” of Gut Microbiota

Oxygen is important to the human body. Cell survival and operations depend on oxygen. When the body becomes hypoxic, it affects the organs, tissues and cells and can cause irreversible damage. Hypoxia can occur under various conditions, including external environmental hypoxia and internal hypoxia. The gut microbiota plays different roles under hypoxic conditions, and its products and metabolites interact with susceptible tissues. This review was conducted to elucidate the complex relationship between hypoxia and the gut microbiota under different conditions. We describe the changes of intestinal microbiota under different hypoxic conditions: external environment and internal environment. For external environment, altitude was the mayor cause induced hypoxia. With the increase of altitude, hypoxia will become more serious, and meanwhile gut microbiota also changed obviously. Body internal environment also became hypoxia because of some diseases (such as cancer, neonatal necrotizing enterocolitis, even COVID-19). In addition to the disease itself, this hypoxia can also lead to changes of gut microbiota. The relationship between hypoxia and the gut microbiota are discussed under these conditions.

A Study on Fucosyltransferase 2 Gene Polymorphism and Secretion Status Related to Neonatal Necrotizing Enterocolitis

Objective. To detect the single nucleotide polymorphism (SNP) of alpha-(1,2) fucosyltransferase 2 gene (FUT2) and the secretion status in the newborns of Chongqing China and explore the relationship between genotype or phenotype of FUT2 and neonatal necrotizing enterocolitis (NEC). Methods. Newborns who were hospitalized in Children’s Hospital of Chongqing Medical University from August 2014 to December 2015 and in line with the inclusion criteria were chosen as the research subjects; 34 cases of them in accordance with the diagnostic criteria of NEC stage II or III were NEC group, and 36 other cases of them were the control group. Total DNA was extracted from oral epithelial cells of patients which were collected with cotton buds. FUT2 SNP genotype was detected by gene sequencing. H antigen was detected with saliva samples by saliva agglutination inhibition test. Related clinical data were collected for analysis. Results. There are three genotypes on the rs1047781 (A385T) allele of the FUT2 encoding sequence: AA, AT, and TT. The number of genotypes AA, AT, and TT in the NEC group was 9 (26.47%), 12 (35.29%), and 13 (38.24%), respectively. In the control group, the number of genotypes AA, AT, and TT was 12 (33.33%), 17 (47.23%), and 7 (19.44%). There were no differences in genotypes between the two groups according to the chi-square test ( P > 0.05 ). There were 22 cases of secretors (64.7%) and 12 cases of nonsecretors (35.3%) in the NEC group. The number of secretors and nonsecretors in the control group was 31 (88.89%) and 5 (11.11%). Statistical difference was found in the phenotype between two groups through the chi-square test ( P < 0.05 ). In addition, no G428A homozygous mutation, which causes nonsecretor phenotype in Caucasians, was seen in all the subjects of this study. Conclusions. These findings indicate that secretion status (nonsecretor) was significantly associated with NEC in Chongqing, China.

Prenatal antibiotic therapy as a risk factor for Neonatal Necrotizing Enterocolitis

The aim of this study was to determine whether there is an association between antenatal antibi-otic exposure and the incidence of necrotizing enterocolitis (NEC) in low birth weight infants.Study design: A retrospective case-control study was conducted on all infants with NEC who were born between 201 0 and 2020. Medical histories of all infants diagnosed with NEC ≥ Bella IIA stage and corresponding controls without NEC were examined. Maternal and newborn char-acteristics were compared using the Cochran-Mantel-Haenszel method, and logistic regression models were constructed to account for bias.Results. Clinical data were analyzed for 97 matched pairs. The adjusted odds ratio (OR) for pre-natal ampicillin exposure was significantly higher for infants who developed NEC (OR 2.3, 95% CI 1.1,4.8, P = 0.003) than for children in the control group. Infants who developed NEC were more likely to have a history of intrauterine exposure to ampicillin in the immediate prenatal period than infants who did not develop NEC.

Neonatal necrotizing enterocolitis-associated DNA methylation signatures in the colon are evident in stool samples of affected individuals

Aim: Neonatal necrotizing enterocolitis (NEC) is a deadly and unpredictable gastrointestinal disease, for which no biomarker exists. We aimed to describe the methylation patterns in stool and colon from infants with NEC. Methods: We performed a high-resolution genome-wide epigenomic analysis using solution-phase hybridization and next-generation sequencing of bisulfite-converted DNA. Results: Our data reveal significant genomic hypermethylation in NEC tissues compared with non-NEC controls. These changes were more pronounced in regions outside CpG islands and gene regulatory elements, suggesting that NEC-specific hypermethylation is not a nonspecific global phenomenon. Conclusions: This study provides evidence of a methylomic signature associated with NEC that is detectable noninvasively and provides a new opportunity for the development of a novel diagnostic method for NEC.

Estimating Neonatal Necrotizing Enterocolitis Based on Feeding Practices

(1) Background: The relationship between enteral nutrition and neonatal necrotizing enterocolitis (NEC) among premature neonates is still unclear. The present work was designed to assess the relationship between NEC and feeding strategies compared to control infants. (2) Methods: A retrospective case-control study of premature infants (<35 weeks’ gestation) with or without NEC that examined feeding practices and clinical characteristics at birth and 3, 7, and 14-day hospitalization, with a longitudinal and cross-sectional analysis. (3) Results: A total of 100 newborns with NEC diagnosis and 92 neonates without the disease with similar demographic and clinical characteristics were included. The median day of NEC diagnosis was 15 days (Interquartile Range (IQR) 5–25 days). A significantly higher number of neonates that were fasting on days 7 and 14 developed NEC (p < 0.05). In the longitudinal analysis, generalized linear and mixed models were fit to evaluate NEC association with feeding strategies and showed that exclusive mother’s own milk (MM) and fortified human milk (FHM) across time were significantly less likely associated with NEC (p < 0.001) and that enteral fasting was positively related with NEC. In the cross-sectional analysis, a binary logistic regression model was fit and predicted 80.7% of NEC cases. MM was also found to correlate with a reduced risk for NEC (OR 0.148, 95% CI 0.044–0.05, p = 0.02), and in particular, on day 14, several factors were related to a decreased odd for NEC, including birth weight, antenatal steroids, and the use of FHM (p < 0.001). (4) Conclusions: MM and FHM were associated with less NEC compared to fasting on days 7 and 14. Feeding practices in Neonatal Intensive Care Units (NICUs) should promote exclusive MM across the two-week critical period as a potential guideline to improve NEC outcome.

Toll-like receptor 4-mediated necroptosis in the development of necrotizing enterocolitis

Background Dramatic intestinal epithelial cell death leading to barrier dysfunction is one of the mechanism of neonatal necrotizing enterocolitis (NEC), in which Toll-like receptor 4 (TLR4) plays a pivotal role. This study explored the role of necroptosis, a drastic way of cell death in NEC. Methods The expression of necroptotic proteins was tested in NEC intestinal tissue and compared with controls. NEC was induced in neonatal wild-type mice and a necroptosis inhibitor was given to investigate whether NEC could be relieved. The general condition, macroscopic scoring, and histological evaluations were performed. The expression of tight junction proteins, inflammatory cytokines, and necroptosis-related proteins was measured, and barrier function was examined. Then, NEC was induced in TLR4-knockout pups to confirm the role of TLR4 in necroptosis. Results Necroptotic proteins were significantly upregulated in both NEC patient and animal models, together with the expression of TLR4. NEC could be relieved and inflammatory infiltration was decreased by necrostatin-1s. TLR4-knockout mice showed milder tissue degradation and less necroptosis after NEC induction. Conclusions Necroptosis is an essential pathological process of NEC. TLR4 may be one stimulator of necroptosis in NEC. Inhibiting the intestinal cell necroptosis might be a useful strategy in the treatment of NEC. Impact Necroptosis is a key pathological process in NEC, which appears to involve TLR4. Anti-necroptosis treatment is a promising strategy that could significantly relieve the symptoms of NEC.