Butyrate protects the intestinal barrier by upregulating Fut2 expression via MEK4-JNK signaling pathway activation.

BACKGROUND: Necrotizing enterocolitis (NEC) is a severe gastrointestinal inflammatory disease in neonates. Fucosyltransferase 2 (Fut2) regulates intestinal epithelial cell fucosylation. In this study, we aimed to investigate butyrate-mediated upregulation of Fut2 expression and the underlying mechanisms. METHODS: In vivo and in vitro models were established. SP600125 was used to inhibit the MEK4-JNK pathway, and anisomycin was used to activate the MEK4-JNK pathway. Fut2, occludin, and ZO-1 expressions were assessed. Furthermore, intestinal permeability was analyzed by FITC-Dextran. The expression of proteins in the MEK-4-JNK pathway was examined by western blotting. RESULTS: In vivo, the addition of exogenous butyrate notably upregulated Fut2, occludin, and ZO-1 expressions and reduced intestinal permeability in mice with NEC. Butyrate may increase the phosphorylation of MEK4, JNK, and c-jun, which are key components of the MEK4-JNK pathway. Additionally, SP600125 inhibited their phosphorylation, which was reversed by anisomycin treatment. In vitro, butyrate substantially increased occludin and ZO-1 expressions. Butyrate considerably increased Fut2 expression and markedly upregulated p-MEK4, p-JNK, and p-c-jun expressions. SP600125 administration decreased their expressions, while anisomycin administration increased their expressions. CONCLUSION: Butyrate upregulated Fut2 expression via activation of the MEK4-JNK pathway, improved intestinal barrier integrity, and protected neonatal mice from NEC. IMPACT: We found that exogenous butyrate could improve intestinal barrier integrity and protect against NEC in neonatal mice. Our data showed that exogenous butyrate supplementation upregulated Fut2 expression by activating the MEK4-JNK pathway. Our study provides novel insights into the pathogenesis of NEC, thereby laying an experimental foundation for future clinical research on the use of butyrate in NEC treatment.

Risk factors for necrotizing enterocolitis in small-for-gestational-age infants: a matched case-control study.

Few studies have focused on the risk factors for necrotizing enterocolitis (NEC) in small for gestational age (SGA) infants. The aim of this study was to identify the risk factors for NEC in SGA newborns. This study included consecutive SGA neonates admitted to a tertiary hospital in Jiangxi Province, China from Jan 2008 to Dec 2022. Patients with NEC (Bell's stage ≥ II) were assigned to the NEC group. Gestational age- and birth weight-matched non-NEC infants born during the same period at the same hospital were assigned to the control group. The risk factors associated with NEC were analyzed with univariate and logistic regression models. During the study period, 2,912 SGA infants were enrolled, 150 (5.15%) of whom developed NEC. In total, 143 patients and 143 controls were included in the NEC and control groups, respectively. Logistic regression analysis revealed that sepsis (OR 2.399, 95% CI 1.271-4.527, P = 0.007) and anemia (OR 2.214, 95% CI 1.166-4.204, P = 0.015) might increase the incidence of NEC in SGA infants and that prophylactic administration of probiotics (OR 0.492, 95% CI 0.303-0.799, P = 0.004) was a protective factor against NEC. Therefore, sepsis, anemia and a lack of probiotic use are independent risk factors for NEC in SGA infants.

Gut microbiota in infants with food protein enterocolitis.

BACKGROUND: We explored the effects of two formulas, extensively hydrolyzed formula (EHF) and amino acid-based formula (AAF), on the gut microbiota and short-chain fatty acids (SCFAs) in infants with food protein-induced enterocolitis syndrome (FPIES). METHODS: Fecal samples of thirty infants with bloody diarrhea receiving EHF or AAF feeding were collected at enrollment, diagnosis of FPIES, and four weeks after diagnosis. The gut microbiota and SCFAs were analyzed using 16 S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. RESULTS: Microbial diversity of FPIES infants was significantly different from that of the controls. FPIES infants had a significantly lower abundance of Bifidobacterium and a higher level of hexanoic acid compared with controls. In EHF-fed FPIES infants, microbial richness was significantly decreased over time; while the microbial diversity and richness in AAF-fed FPIES infants exhibited no differences at the three time points. By four weeks after diagnosis, EHF-fed FPIES infants contained a decreased abundance of Acinetobacter, whereas AAF-fed FPIES infants contained an increased abundance of Escherichia-Shigella. EHF-fed infants experienced significantly decreased levels of butyric acid and hexanoic acid at four weeks after diagnosis. CONCLUSIONS: Infants with FPIES had intestinal dysbiosis and different formulas differentially affected gut microbiota and SCFAs in FPIES infants. IMPACT: We firstly report the impacts of two different nutritional milk formulas on the gut microbial composition and SCFAs levels in infants with FPIES. We show that infants with FPIES have obvious intestinal dysbiosis and different formulas differentially affect gut microbiota and SCFAs in FPIES infants. Understanding the effects of different types of formulas on gut microbial colonization and composition, as well as the related metabolites in infants with FPIES could help provide valuable insights for making choices about feeding practices.

Exogenous autoinducer-2 alleviates intestinal damage in necrotizing enterocolitis via PAR2/MMP3 signaling pathway.

BACKGROUND: Imbalanced intestinal microbiota and damage to the intestinal barrier contribute to the development of necrotizing enterocolitis (NEC). Autoinducer-2 (AI-2) plays a crucial role in repairing intestinal damage and reducing inflammation. OBJECTIVE: This study aimed to investigate the impact of AI-2 on the expression of intestinal zonula occludens-1 (ZO-1) and occludin proteins in NEC. We evaluated its effects in vivo using NEC mice and in vitro using lipopolysaccharide (LPS)-stimulated intestinal cells. METHODS: Pathological changes in the intestines of neonatal mice were assessed using histological staining and scoring. Cell proliferation was measured using the cell counting kit-8 (CCK-8) assay to determine the optimal conditions for LPS and AI-2 interventions. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the mRNA levels of matrix metalloproteinase-3 (MMP3), protease activated receptor-2 (PAR2), interleukin-1ß (IL-1ß), and IL-6. Protein levels of MMP3, PAR2, ZO-1, and occludin were evaluated using western blot, immunohistochemistry, or immunofluorescence. RESULTS: AI-2 alleviated NEC-induced intestinal damage (P < 0.05) and enhanced the proliferation of damaged IEC-6 cells (P < 0.05). AI-2 intervention reduced the mRNA and protein expressions of MMP3 and PAR2 in intestinal tissue and cells (P < 0.05). Additionally, it increased the protein levels of ZO-1 and occludin (P < 0.05), while reducing IL-1ß and IL-6 mRNA expression (P < 0.05). CONCLUSION: AI-2 intervention enhances the expression of tight junction proteins (ZO-1 and occludin), mitigates intestinal damage in NEC neonatal mice and IEC-6 cells, potentially by modulating PAR2 and MMP3 signaling. AI-2 holds promise as a protective intervention for NEC. AI-2 plays a crucial role in repairing intestinal damage and reducing inflammation.

[Recent research on machine learning in the diagnosis and treatment of necrotizing enterocolitis in neonates]. / æœºå™¨å­¦ä¹ åœ¨æ–°ç”Ÿå„¿åæ­»æ€§å°è‚ ç»“è‚ ç‚Žè¯Šç–—ä¸­çš„ç ”ç©¶è¿›å±•.

Necrotizing enterocolitis (NEC), with the main manifestations of bloody stool, abdominal distension, and vomiting, is one of the leading causes of death in neonates, and early identification and diagnosis are crucial for the prognosis of NEC. The emergence and development of machine learning has provided the potential for early, rapid, and accurate identification of this disease. This article summarizes the algorithms of machine learning recently used in NEC, analyzes the high-risk predictive factors revealed by these algorithms, evaluates the ability and characteristics of machine learning in the etiology, definition, and diagnosis of NEC, and discusses the challenges and prospects for the future application of machine learning in NEC.

Changes of gut microbiota and tricarboxylic acid metabolites may be helpful in early diagnosis of necrotizing enterocolitis: A pilot study.

Purpose: We aimed to explore the value of gut microbiota and tricarboxylic acid (TCA) metabolites in early diagnosis of necrotizing enterocolitis (NEC) among infants with abdominal manifestations. Methods: Thirty-two preterm infants with abdominal manifestations at gestational age ≤ 34 weeks were included in the study and were divided into non-NEC (n = 16) and NEC (n = 16) groups. Faecal samples were collected when the infants were enrolled. The gut microbiota was analysed with high-throughput sequencing, and TCA metabolites were measured with multiple reaction monitoring (MRM) targeted metabolomics. Receiver operating characteristic (ROC) curves were generated to explore the predictive value of the obtained data. Results: There was no significant difference in alpha diversity or beta diversity between the two groups (p > 0.05). At the phylum level, Proteobacteria increased, and Actinomycetota decreased in the NEC group (p < 0.05). At the genus level, Bifidobacterium and Lactobacillaceae decreased significantly, and at the species level, unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis decreased in the NEC group (p < 0.05). Further Linear discriminant analysis effect sizes (LEfSe) analysis showed that the change in Proteobacteria at the phylum level and Lactobacillaceae and Bifidobacterium at the genus level scored higher than 4. The concentrations of succinate, L-malic acid and oxaloacetate in the NEC group significantly increased (p < 0.05), and the areas under the ROC curve for these metabolites were 0.6641, 0.7617, and 0.7344, respectively. Conclusion: Decreased unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis at the species level as well as the increase in the contents of some TCA metabolites, including succinate, L-malic acid and oxaloacetate, have potential value for the early diagnosis of NEC.

Fecal HBD-2 and Claudin-3 may be potential biomarkers to predict the deterioration of necrotizing enterocolitis: A prospective study.

Background and purpose: Necrotizing enterocolitis (NEC) is a critical gastrointestinal disease. We aim to explore the value of fecal human ß-defensin 2 (HBD-2), Claudin-3, high-mobility group box-1 protein (HMGB-1), and resistin-like molecule ß (Relmß) as well as some laboratory metrics to predict the deterioration of NEC. Methods: Infants diagnosed with NEC at Stage II were enrolled in our study. Those who progressed to Stage III were included in the Stage III group and the rest were included in the Stage II group. Clinical data and laboratory metrics of the infants were collected. Fecal samples of HBD2, HMGB-1, Claudin-3, and Relmß collected during their enrollment were determined by using enzyme-linked immunosorbent assay (ELISA) kits. Student's t-test, the Mann-Whitney U test, the chi-square test, receiver operating characteristic (ROC), and logistic regression analysis were performed. Results: Sixty infants diagnosed with NEC at Stage II were enrolled in our study, with 27 in the Stage III group (n = 27) and 33 in the Stage II group (n = 33). Although many of these NEC cases were late preterm and term infants, the infants in the Stage III group had a lower gestational age (P < 0.05). The incidence of gestational diabetes mellitus, peritonitis, intestinal adhesion, and sepsis was higher and more infants in the Stage III group underwent surgeries (P < 0.05). The levels of HBD-2 and Claudin-3 were higher and neutrophil count was lower in the Stage III group than in the Stage II Group, and the area under the curve (AUC) was 0.754, 0,755, and 0.666, respectively (P < 0.05). HBD-2 ≥ 1649.02 ng/g and Claudin-3 ≥ 2488.71 pg/g were included in the multivariate stepwise logistic regression analysis (P < 0.05), and the AUC of the model was 0.805 (95% CI: 0.688-0.922). Conclusion: Fecal HBD-2 and Claudin-3 may be potential biomarkers to predict the deterioration of NEC from Stage II to Stage III.

Alterations of the gut microbiota and short chain fatty acids in necrotizing enterocolitis and food protein-induced allergic protocolitis infants: A prospective cohort study.

Background: Even though presenting with similar clinical manifestations, necrotizing enterocolitis (NEC) and food protein-induced allergic protocolitis (FPIAP) have completely different treatments and prognosis. Our study aimed to quantify and evaluate differences in gut microbiota and short chain fatty acids (SCFAs) between infants with NEC and FPIAP to better identify these two diseases in clinical settings. Methods: A total of 43 infants with NEC or FPIAP in Children's Hospital of Chongqing Medical University, China between December 2020 and December 2021 were enrolled. Stool samples were prospectively collected and froze. Infants defined as NEC were those who presented with clinical courses consistent with NEC and whose radiographs fulfilled criteria for Bell's stage 2 or 3 NEC, while those who were healthy in appearance and had blood in the stool (visible or may be microscopic), had normal bowel sounds in physical examination, were resolved after eliminating the causative food, and/or had recurrence of symptoms after oral food challenge (OFC) were defined as FPIAP. Primers specific for bacterial 16S rRNA genes were used to amplify and pyrosequence fecal DNA from stool samples. Gas chromatography-mass spectrometry (GC-MS) technology was used to determine the concentrations of SCFAs. Results: Among the 43 infants, 22 were diagnosed with NEC and 21 were diagnosed with FPIAP. The microbial community structure in NEC infant stools differed significantly from those in FPIAP infant stools. NEC infants had significantly higher proportion of Actinobacteria and reduced proportion of Bacteroidetes compared with FPIAP infants, and the proportions of Halomonas, Acinetobacter, Bifidobacterium, and Stenotrophomonas in NEC infants were significantly higher than that of FPIAP infants. In addition, infants with NEC had significantly lower levels of acetic acid, propionic acid, butyric acid, isovaleric acid, and total SCFAs, and higher level of hexanoic acid as compared to the infants of the FPIAP group. Conclusions: The differences of gut microbiota composition and concentrations of SCFAs might represent suitable biomarker targets for early identification of NEC and FPIAP.

Succinate aggravates intestinal injury in mice with necrotizing enterocolitis.

Background: Necrotizing enterocolitis (NEC) is the most prevalent gastrointestinal disorder that predominantly threatens preterm newborns. Succinate is an emerging metabolic signaling molecule that was recently studied in relation to the regulation of intestinal immunity and homeostasis. We aimed to investigate the relationship between NEC and gut luminal succinate and preliminarily explored the effect of succinate on NEC pathogenesis. Methods: Fecal samples from human neonates and mouse pups were analyzed by HPLC - MS/MS and 16S rRNA gene sequencing. C57BL/6 mice were randomly divided into four groups: control, NEC, Lsuc, and Hsuc. The mortality, weight gain, and intestinal pathological changes in four mouse groups were observed. Inflammatory cytokines and markers of macrophages were identified by quantitative real-time PCR. Succinate receptor 1 (SUCNR1) localization was visualized by immunohistochemistry. The protein levels of SUCNR1 and hypoxia-inducible factor 1a (HIF-1a) were quantified by western blotting. Results: The levels of succinate in feces from NEC patients were higher than those in feces from non-NEC patients (P <0.05). In the murine models, succinate levels in intestinal content samples were also higher in the NEC group than in the control group (P <0.05). The change in succinate level was closely related to intestinal flora composition. In samples from human neonates, relative to the control group, the NEC group showed a higher abundance of Enterobacteriaceae and a lower abundance of Lactobacillaceae and Lactobacillus (P <0.05). In the murine models, relative to the control group, increased abundance was observed for Clostridiaceae, Enterococcaceae, Clostridium_sensu_stricto_1, and Enterococcus, whereas decreased abundance was observed for Lactobacillaceae and Lactobacillus (P <0.05). Increased succinate levels prevented mice from gaining weight, damaged their intestines, and increased their mortality; upregulated the gene expression of interleukin-1ß (IL-1ß), IL-6, IL-18 and tumor necrosis factor (TNF); and downregulated the gene expression of IL-10 and transforming growth factor (TGF)-ß. Exogenous succinic acid increased inducible nitric oxide synthase (iNOS) gene expression but decreased Arginase-1 (Arg1) gene expression; and increased the protein expression of SUCNR1 and HIF-1a. Conclusion: Succinate plays an important role in the development of necrotizing enterocolitis severity, and the activation of the HIF-1a signaling pathway may lead to disease progression.

Gut microbiota and short-chain fatty acids may be new biomarkers for predicting neonatal necrotizing enterocolitis: A pilot study.

Background: Dysbacteriosis 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 methods: Thirty-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). Results: The 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. Conclusion: The 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.

Serum Relmß combined with abdominal signs may predict surgical timing in neonates with NEC: A cohort study.

Aims: To examine the predictive value of serum biomarkers combined with other indicators for necrotizing enterocolitis (NEC) surgery decision-making. Methods: Clinical data, including baseline information, clinical features, imaging presentation and serum assessment, of the infants enrolled were collected, and the serum concentrations of HBD2, HMGB-1, Claudin-3 and Relmß were determined. Student's t test, the Mann-Whitney U test, the chi-square test and logistic regression analysis were used. Receiver operating characteristic (ROC) curves were also generated. Results: Forty-nine infants were enrolled, with 23 in the surgical NEC group and 26 in the medical NEC group. There were no differences in the baseline clinical information, including birth weight, gestational age, admission age and risk factors, during pregnancy and before enrollment (P > 0.05). Peritonitis, intestinal adhesion and sepsis were more common in the surgical group (P < 0.05). The incidences of abdominal distention, abdominal wall tenseness, abdominal tenderness and absent bowel sounds in the surgical group were significantly higher when NEC occurred (P < 0.05). There were no differences between the two groups in the imaging presentation (P > 0.05). The concentration of Relmß {[8.66 (4.29, 19.28) vs. 20.65 (9.51, 44.65)]} in the surgical group was significantly higher (P < 0.05). Abdominal wall tenseness, abdominal tenderness and a Relmß concentration > 19.7 µmol/L were included in the predictive model, and the AUC of the predictive score was 0.943 (95% CI: 0.891-1.000) (P < 0.05). Conclusion: Serum Relmß concentration combined with abdominal wall tenseness and abdominal tenderness may be useful in determining surgical timing in neonates with NEC.

[Influence of enteral feeding initiation time on intestinal flora and metabolites in very low birth weight infants: a prospective study]. / ä¸åŒè‚ å† è¥å »å¼€å§‹æ—¶é—´å¯¹æžä½Žå‡ºç”Ÿä½“é‡å„¿è‚ é“èŒç¾¤åŠä»£è°¢äº§ç‰©å½±å“çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the influence of enteral feeding initiation time on intestinal flora and metabolites in very low birth weight (VLBW) infants. METHODS: A total of 29 VLBW infants who were admitted to the Department of Neonatology, Children's Hospital of Chongqing Medical University, from June to December, 2020, were enrolled as subjects. According to the enteral feeding initiation time after birth, the infants were divided into two groups: <24 hours (n=15) and 24-72 hours (n=14). Fecal samples were collected at weeks 2 and 4 of hospitalization, and 16S rDNA high-throughput sequencing and gas chromatography-mass spectrometry were used to analyze the microflora and short-chain fatty acids (SCFAs) respectively in fecal samples. RESULTS: The analysis of microflora showed that there was no significant difference between the two groups in Chao index (reflecting the abundance of microflora) and Shannon index (reflecting the diversity of microflora) at weeks 2 and 4 after birth (P>0.05). The analysis of flora composition showed that there was no significant difference in the main microflora at the phylum and genus levels between the two groups at weeks 2 and 4 after birth (P>0.05). The comparison of SCFAs between the two groups showed that the <24 hours group had a significantly higher level of propionic acid than the 24-72 hours group at week 4 (P<0.05), while there was no significant difference in the total amount of SCFAs and the content of the other SCFAs between the two groups (P>0.05). CONCLUSIONS: Early enteral feeding has no influence on the diversity and abundance of intestinal flora in VLBW infants, but enteral feeding within 24 hours can increase the level of propionic acid, a metabolite of intestinal flora.

Risk Factors and Clinical Characteristics of Neonatal Acute Respiratory Distress Syndrome Caused by Early Onset Sepsis.

Purpose: To identify risk factors associated with the development of acute respiratory distress syndrome (ARDS) in infants with early onset sepsis (EOS) and to describe the clinical features. Methods: A retrospective study was conducted at the Children's Hospital of Chongqing Medical University between January 2000 and October 2020. The infants were divided into ARDS and non-ARDS groups. Clinical characteristics and risk factors were compared between the two groups. Results: Two hundred fifty infants (58 with ARDS) were included. Smaller gestational age, lower birth weight (LBW), lower serum albumin level, a higher rate of preterm birth, premature rupture of membranes, antenatal steroid exposure, and lower Apgar score were associated with an increased development of ARDS by univariate analysis (P < 0.05). LBW (ß = -0.001, P = 0.000, OR: 0.999, 95% CI: 0.998-0.999) and low serum albumin levels (ß = -0.063, P = 0.022, OR: 0.939, 95% CI: 0.889-0.991) were identified as independent risk factors for the development of ARDS by logistic regression analysis. A higher frequency of complications, including persistent pulmonary hypertension, intraventricular hemorrhage, pulmonary hemorrhage, septic shock, and bronchopulmonary dysplasia, was found in the ARDS group (P < 0.05). The rate of mortality was higher for those in the ARDS group than for those in the non-ARDS group (46.6% vs. 15.6%, χ2 = 24.205, P = 0.000). Conclusion: Acute respiratory distress syndrome (ARDS) in EOS could lead to a higher frequency of complications and mortality. The risk factors for the development of ARDS were LBW and low serum albumin levels.

Differences in the Gut Microbiota Composition and Metabolites Associated With Feeding Intolerance in VLBW Infants With a Gestational Age of ≤ 30 Weeks: A Pilot Study.

OBJECTIVE: To explore the main variations in gut microbiota compositions, short-chain fatty acids (SCFAs) concentrations and autoinducer-2 (AI-2) levels in very-low-birth-weight (VLBW) infants with feeding intolerance (FI). METHODS: Twenty-seven VLBW infants with gestational ages of ≤30 weeks were divided into the FI group (n=14) and feeding tolerance (FT) group (n=13). The gut microbiota composition and SCFAs concentrations and AI-2 levels in feces were detected at 2 and 4 weeks after birth. RESULTS: There was no difference in alpha diversity between the two groups at 2 and 4 weeks after birth (P>0.05). Although the Chao index decreased (P<0.05), there was no difference in the Shannon index from 2 weeks to 4 weeks in either the FI or FT group (P>0.05). Additionally, there was no difference in beta diversity between the FI and FT groups at 2 weeks (P>0.05), but there was a significant difference in beta diversity between the two groups at 4 weeks (P<0.05) and a large difference from 2 weeks to 4 weeks in both the FI and FT groups (P<0.05). Furthermore, the composition of the microbiota at 4 weeks was significantly different from that at 2 weeks in the FI group (P<0.05). The Veillonella abundance was lower at 4 weeks in the FI group (P<0.05), but there were no differences in the compositions of the other main microbes between the two groups (P>0.05). Proteobacteria and Firmicutes were dominant in both the FI and FT groups. The concentrations of propanoic, valeric and hexanoic acids were lower in the FI group at 2 weeks, and the levels of isobutyric and valeric acids were lower at 4 weeks after birth (P<0.05). The areas under the curves (AUCs) of propanoic, butanoic and valeric acids in predicting FI were 0.878, 0.816 and 0.744, respectively. Compared with that in the FT group, the relative bioluminescence of AI-2 was lower in the FI group at 2 weeks (P<0.05), and the AUC was 0.736. CONCLUSIONS: The main composition of the microbiota was not obviously different in infants with FI. Some SCFAs and AI-2 have moderate value in predicting FI.

Mental health and social support among nurses during the COVID-19 pandemic.

This study aimed to investigate the prevalence of mental problems and social support among nurses during the COVID-19 epidemic and to explore the correlation. We carried out a multicentre, large-sample questionnaire survey in Chongqing (China). The WeChat-based survey program Questionnaire Star was used to distribute a questionnaire with self-designed items to obtain general information, the Depression, Anxiety and Stress Scale-21 (DASS-21), and the Social Support Rating Scale (SSRS). A total of 848 neonatal nurses participated. The results showed that 104 nurses (12.3%) had depression symptoms, 133 (15.7%) had anxiety symptoms, and 45 (5.3%) had stress symptoms. However, the DASS-21 score of the majority of nurses was normal. Pearson correlation analyses revealed that mental health was negatively correlated with social support, indicating that the higher social support was, the better the psychological condition of nurses.

Long-term effect of active parenteral nutrition support regimen in preterm infants with a gestational age of <34 weeks. / ç§¯æžè‚ å¤–è¥å »æ”¯æŒæ–¹æ¡ˆåœ¨èƒŽé¾„å°äºŽ34å‘¨æ—©äº§å„¿ä¸­çš„è¿œæœŸæ•ˆæžœç ”ç©¶.

OBJECTIVES: To study the long-term effect of active parenteral nutrition support regimen in preterm infants with a gestational age of <34 weeks. METHODS: According to the different doses of fat emulsion and amino acids used in the early stage, the preterm infants with a gestational age of <34 weeks, who were admitted to the hospital within 24 hours after birth from May to December 2019, were divided into an active parenteral nutrition group and a conventional parenteral nutrition group (n=50). Physical indices and the measurements of the Gesell Development Scale were collected at the age of 6 months and 13 months. RESULTS: At the age of 6 months, the active parenteral nutrition group (n=46) had higher developmental quotients of gross motor, fine motor, and personal-social behavior than the conventional parenteral nutrition group (n=34) (P<0.05). At the age of 13 months, the active parenteral nutrition group (n=25) had higher developmental quotients of adaptive behavior, gross motor, and personal-social behavior than the conventional parenteral nutrition group (n=19) (P<0.05). There were no significant differences in the physical development indices such as body weight, body height, and head circumference between the two groups during follow-up (P>0.05). CONCLUSIONS: For preterm infants with a gestational age of <34 weeks, an active parenteral nutrition support strategy with high doses of fat emulsion and amino acids within 24 hours after birth can improve their long-term neurodevelopment.

Effect of the course of treatment with broad-spectrum antibiotics on intestinal flora and short-chain fatty acids in feces of very low birth weight infants: a prospective study. / å¹¿è°±æŠ—ç”Ÿç´ ç–—ç¨‹å¯¹æžä½Žå‡ºç”Ÿä½“é‡å„¿ç²ªä¾¿è‚ é“èŒç¾¤å’ŒçŸ­é“¾è„‚è‚ªé ¸å½±å“çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the effect of the course of treatment with broad-spectrum antibiotics on intestinal flora and short-chain fatty acids (SCFAs) in feces of very low birth weight (VLBW) infants. METHODS: A total of 29 VLBW infants who were admitted to the Neonatal Diagnosis and Treatment Center of Children's Hospital Affiliated to Chongqing Medical University from June to December 2020 were enrolled as subjects for this prospective study. According to the course of treatment with broad-spectrum antibiotics, they were divided into two groups: ≤7 days (n=9) and >7 days (n=20). Fecal samples were collected on days 14 and 28 of hospitalization, and 16S rDNA high-throughput sequencing and gas chromatography-mass spectrometry were used to analyze the flora and SCFAs in fecal samples. RESULTS: There was a significant reduction in Chao index of the intestinal flora in the ≤7 days group and the >7 days group from week 2 to week 4 (P<0.05). In the ≤7 days group, there were significant increases in the proportions of Firmicutes and Clostridium_sensu_stricto_1 and a significant reduction in the proportion of Proteobacteria from week 2 to week 4 (P<0.05). At week 4, compared with the ≤7 days group, the >7 days group had significant reductions in the proportions of Firmicutes and Clostridium_sensu_stricto_1 and a significant increase in the proportion of Proteobacteria (P<0.05), as well as significant reductions in the content of isobutyric acid and valeric acid (P<0.05). CONCLUSIONS: The course of treatment with broad-spectrum antibiotics can affect the abundance, colonization, and evolution of intestinal flora and the content of their metabolites SCFAs in VLBW infants. The indication and treatment course for broad-spectrum antibiotics should be strictly controlled in clinical practice.

Sodium Butyrate Alleviates Intestinal Inflammation in Mice with Necrotizing Enterocolitis.

OBJECTIVE: To determine the role of sodium butyrate in intestinal inflammation via regulation of high-mobility group box-1 (HMGB1), we analyzed the potential mechanism in necrotizing enterocolitis (NEC) in a neonatal mouse model. METHODS: A NEC model was created with hypoxia and cold exposure and artificial overfeeding. C57BL/6 neonatal mice were randomized into three groups: the control, untreated NEC, and sodium butyrate (150 mM)-pretreated NEC groups. Pathological variations in ileocecal intestinal tissue were observed by HE staining and scored in a double-blind manner. The mRNA expression levels of HMGB1, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and inflammatory cytokines in intestinal tissues were determined by quantitative real-time PCR. The protein levels of HMGB1 and associated cytokines in intestinal tissues were evaluated using ELISA. The relative protein expression levels of TLR4 and NF-κB in intestinal tissues were quantified by western blot. RESULTS: Sodium butyrate administration improved the body weight and survival rate of NEC mice; relieved intestinal pathological injury; reduced the intestinal expression of HMGB1, TLR4, NF-κB, interleukin- (IL-) 1ß, IL-6, IL-8, and TNF-α; and increased the intestinal expression of IL-10 (P < 0.05). Treatment with butyrate decreased the proportion of opportunistic Clostridium_sensu_stricto_1 and Enterococcus and increased the proportion of beneficial Firmicutes and Lactobacillus in the NEC model. CONCLUSIONS: Sodium butyrate intervention relieves intestinal inflammation and partially corrects the disrupted intestinal flora in mice with NEC.

Exogenous Autoinducer-2 Rescues Intestinal Dysbiosis and Intestinal Inflammation in a Neonatal Mouse Necrotizing Enterocolitis Model.

Autoinducer-2 (AI-2) is believed to be a bacterial interspecies signaling molecule that plays an important role in the regulation of the physiological behaviors of bacteria. The effect of AI-2 on the process of necrotizing enterocolitis (NEC) is unknown, and the aim of this study was to study the effect of AI-2 in a mouse NEC model. C57BL/6 mouse pups were randomly divided into three groups: the control group, the NEC group, and the NEC+AI-2 (NA) group. Exogenous AI-2 (500 nM) was added to the formula milk of the NA group. The concentrations of fecal AI-2 and flora were tested. The expression of cytokines, TLR4 and NF-κB in intestinal tissue was detected. The AI-2 level was significantly decreased in the NEC group (P<0.05). Compared with the NEC group, the intestinal injury scores, expression of TLR4, NF-kB, and proinflammatory factors (IL-1ß, IL-6, IL-8 and TNF-α) were reduced, and expression of anti-inflammatory factor (IL-10) was increased in the NA group mice (P<0.05). At the phylum level, the Proteobacteria abundance in the NA group was significantly increased, while the Bacteroidota abundance in the control group was significantly increased (P<0.05). At the genus level, Helicobacter and Clostridium_sensu_stricto_1 exhibited significantly greater abundance in the NEC group than in the other two groups, while Lactobacillus had the opposite trend (P<0.05). In addition, the abundances of Klebsiella, Rodentibacter and Enterococcus were significantly higher in the NA group than in the NEC and control groups (P < 0.05). Exogenous AI-2 partially reverses flora disorder and decreases inflammation in an NEC mouse model.

Risk factors of necrotizing enterocolitis in neonates with sepsis: A retrospective case-control study.

Sepsis, a severe infectious disease in the neonatal period, is considered a risk factor for necrotizing enterocolitis (NEC). To investigate the specific risk factors for NEC in septic infants, septic infants admitted to our center from January 2010 to April 2018 were included. Septic neonates with proven NEC (Bell's stage ⩾II) were enrolled in the NEC group, and those without NEC were enrolled in the control group. Demographics, clinical characteristics, and risk factors were compared between the two groups. Univariate and logistic regression analyses were used to evaluate the potential risk factors for NEC. A total of 610 septic neonates were included, of whom 78 (12.8%) had complicated NEC. The univariate analysis indicated that infants with NEC had a lower birth weight, a lower gestational age, and older age on admission than those without NEC (P < 0.05). Higher rates of anemia, prolonged rupture of membranes (PROM) (⩾18 h), pregnancy-induced hypertension, late-onset sepsis (LOS), red blood cell transfusion and hypoalbuminemia were observed in the NEC group than in the non-NEC group (P<0.05). Logistic regression analysis revealed LOS (P = 0.000), red blood cell transfusion (P = 0.001) and hypoalbuminemia (P = 0.001) were associated with the development of NEC. Among NEC infants, those who needed red blood cell transfusion had a longer hospitalization duration than those who did not need transfusion (P < 0.05). LOS, red blood cell transfusion and hypoalbuminemia were independent risk factors for the development of NEC in infants with sepsis. Taking measures to reduce the occurrence of hypoproteinemia and severe anemia may help to reduce the occurrence of NEC in septic neonates.