Newborn infants are prone to sepsis and related inflammation of different organs. Neuroinflammation has been associated with long-term adverse neuronal (neuropsychiatric/neurodegenerative) outcomes, including attention deficit hyperactivity disorder (ADHD) or even Alzheimer's disease. Despite a vast number of findings on sepsis-induced inflammatory responses in the central nervous system (CNS), how neuroinflammation affects brain development remains largely elusive. In this study, neonates with clinical sepsis and screened for meningitis were included and classified by the neuroinflammation status based on cerebrospinal fluid (CSF) parameters (INF vs. NOINF). CSF samples collected from clinical screening were subjected to proteomics analysis. Proteins with differential abundance were subjected to enrichment analysis to reveal affected biological pathways. INF and NOINF infants had similar demographic data and hematological and biochemical parameters in blood and CSF. The CSF proteomes were essentially different between the two groups. All 65 proteins with differential abundance showed lower abundance in the INF group and functionally covered pivotal developmental processes, including axonal and synaptic function and extracellular homeostasis. CSF proteins, PTPRZ1 and IGFBP4, were correlated with C-reactive protein (CRP) and ratios of immature/total neutrophils in blood. In general, a substantial change in the CSF protein profile was found under neuroinflammation, and these changes are related to systemic conditions. The results suggest that changes in CSF proteins may be involved in sepsis-affected neurodevelopment, such as disturbances in circuit formation, which has the potential to predispose neonates to long-term adverse outcomes.
Enterotoxigenic Escherichia coli (ETEC) is closely associated with diarrhoea in children in resource-limited countries. This study aims to investigate the change of the mucosal microbiome and protein expression in the ileum induced by E. coli K88 (ETEC) using pigs as a model. Seven weaned male pigs were orally given ETEC (1 × 109 CFU, n = 7), and the other seven received saline (CON, n = 7). Ileal tissues were obtained 48 hours after the ETEC challenge for both proteomic and mucosal microbiome analyses. Nine proteins were found with altered abundance between the two groups, including a decrease in FABP1 and FABP6, involved in bile acid circulation. The TLR-9 mediated pathway was also affected showing increased transcription of genes SIGIRR and MyD88. Correlations between the ileal proteins and mucosal bacterial taxa found included a positive correlation between Lactobacilli and PPP3CA (r = 0.9, p < 0.001) and a negative correlation between Prevotella with CTNND1 (r = −0.7, p < 0.01). In conclusion, ETEC infection caused inflammation and impaired the circulation of bile acids and the mucosal microbiome may affect the expression of intestinal proteins. Further studies are needed to explain the exact roles of these affected processes in the pathogenesis of ETEC-triggered diarrhoea.
Findings on prenatal polyunsaturated fatty acids (PUFA) and offspring allergies have been inconsistent, and the majority of studies have focused on Western populations. This study aimed to investigate the associations between maternal erythrocyte PUFA and offspring allergies in the first 2 years in the Chinese population. We included 573 mother–infant pairs from a birth cohort. Based on the outpatient medical records, we identified the diagnosis and time of offspring allergic disease onset. We measured erythrocyte fatty acids by gas chromatography. Associations were examined using Cox regression. We found that higher maternal total PUFA levels (HR = 0.80; 95% CI: 0.68, 0.94), especially of arachidonic acid (AA) (HR = 0.79; 95% CI: 0.65, 0.97) and n-3 PUFA (HR = 0.77; 95% CI: 0.62, 0.97), were associated with reduced risk of offspring allergies. Similar results were found for eczema. Compared with children without a maternal allergy history, the associations of total PUFA (p = 0.028) and n-6 PUFA (p = 0.013) with offspring allergies were stronger in those with a maternal allergy history. Maternal erythrocyte total PUFA, especially AA, and n-3 PUFA were inversely associated with offspring allergies within 2 years of age. There was a significant interaction between maternal allergy history and maternal PUFA in offspring allergies.
Enterotoxigenic Escherichia coli (ETEC) is closely associated with diarrhoea in children in resource-limited countries and of travellers’ diarrhoea. This study aims to investigate the change of ileal mucosal microbiome and ileal protein expression as well as their correlation in pigs by E. coli K88 (ETEC). Seven weaned male pigs were orally given 1 ×109 CFU of ETEC (ETEC, n = 7), and the other seven received saline (CON, n = 7). Ileal tissues were obtained 48 h after the ETEC challenge for both proteomic and mucosal microbiomic analyses. Nine proteins were altered in expression level in the ETEC group, including decreased expression of FABP1 and FABP6 involved in bile acid circulation. TLR-9 mediated pathway was also affected at transcription level with increased expression of SIGIRR and MyD88. Correlation analysis revealed correlations between the ileal proteins and mucosal bacterial taxa, including the positive correlation between Lactobacilli and PPP3CA (r = 0.9, p < 0.001), and negative correlation between Prevotella with CTNND1 (r = -0.7, p < 0.01). In conclusion, ETEC infection caused inflammation and impaired the circulation of bile acids, and the mucosal microbiome may affect the expression of intestinal proteins. Further studies are needed for exact roles of these affected processes in the pathogenesis of ETEC-triggered diarrhoea.
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