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:Bronchopulmonary dysplasia (BPD) is a major complication of preterm birth, with lasting effects on respiratory outcomes in extremely low birth weight (ELBW) and very low birth weight (VLBW) infants. This pilot study aimed to identify non-invasive salivary microRNA biomarkers for early BPD risk stratification in preterm neonates. Saliva samples were collected from 20 preterm infants (BPD+: n=10; BPD-: n=10) at days 10-14 of life. Total RNA including the miRNA fraction was isolated from saliva using the MagMAX mirVana Total RNA Isolation Kit. RNA was profiled using the Affymetrix GeneChip miRNA 4.1 Array (GeneTitan MC instrument, 96-well plate format). RMA normalization and limma differential expression identified three candidate salivary miRNA biomarkers (hsa-let-7b-5p, hsa-miR-4454, hsa-let-7c-5p), all significantly upregulated in BPD infants.