Project description:Most hospitalized preterm infants receive antibiotics (AB) in the first days of life to treat or prevent systemic infections. Short-term, early AB treatment may also prevent against the microbiota-dependent serious gut disorder, necrotising enterocolitis (NEC). However, it remains a challenge to predict or early detection of NEC in the first weeks of life and few diagnostic markers exist. Using preterm piglets as models for infants, we hypothesised that proteomic profiling could be used to identify new early plasma biomarkers of NEC with or without prior AB treatment. Preterm newborn pigs were treated with saline (CON) or antibiotics (ampicillin, gentamicin, and metronidazole), given enterally (ENT) or parenterally (PAR), and fed formula for four days to induce NEC. The gut was collected for scoring of NEC lesions and blood was collected for haematology and plasma proteomics
Project description:The aim of the EVENT Study (Extracellular Vesicles in Early preterm Neonates and Thrombin generation) was to characterise the circulating EVs in preterm infants, using multiple EV charac- terisation techniques, during the perinatal adaptation period and compare them to healthy full-term controls.
Project description:Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNAseq of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later – or not at all – showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early life microbiome in later life dysmotility.
Project description:Necrotizing enterocolitis (NEC), a severe gut disorder in preterm infants, is difficult to predict due to poor specificity and sensitivity of clinical signs and biomarkers. Using preterm piglets as a model, we hypothesized that early development of NEC affects blood gene expression, potentially related to early systemic immune responses. In this animal model, variable severity of gut NEC lesions were detected in 5d-old piglets with limited clinical signs. NEC (n=20) and control piglets (CON, n=19) were analyzed for whole blood transcriptome, revealing 344 differentially expressed genes (DEGs) between NEC and CON piglets. Co-expression network analyses and qPCR suggested AOAH, FKBP5, PAK2 as three NEC-specific genes associated with severe gut lesions. These results suggest that whole blood gene expressions are affected in preterm piglets when clinical symptoms of NEC are minimal. Blood transcriptome may be a novel tool to identify early biomarkers of NEC.