Project description:There is little information regarding the allergen content of milk feeds in the preterm population. Previous studies have evaluated specific proteins/peptides via ELISA, but no studies have performed a broad analysis of the allergenic peptide content and protease activity of milk feeds in this population. Preterm infants spend a critical window of time for immune development in the Newborn Intensive Care Unit (NICU), and may receive fortified donor milk, maternal milk or formula feeds via nasogastric tube or bottle instead of fresh breastmilk via breastfeeding.
Project description:Necrotizing enterocolitis (NEC) is an acute and life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventative therapy, but potential bacterial infection raise concern. Removal of bacteria from donor feces may reduce this risk while maintaining the NEC-preventive effects. We aimed to assess preclinical efficacy and safety of bacteria-free fecal filtrate transfer (FFT). Using fecal material from healthy suckling piglets, we administered FMT rectally, or cognate FFT either rectally or oro-gastrically to formula-fed preterm, cesarean-delivered piglets as a model for preterm infants, We compared gut pathology and related safety parameters with saline controls, and analyzed ileal mucosal transcriptome to gauge the host e response to FMT and FFT treatments relative to control. Results showed that oro-gastric FFT prevented NEC, whereas FMT did not perform better than control. Moreover, FFT but not FMT reduced intestinal permeability, whereas FMT animals had reduced body weight increase and intestinal growth. Global gene expression of host mucosa responded to FMT but not FFT with increased and decreased bacterial and viral defense mechanisms, respectively. In conclusion, as preterm infants are extremely vulnerable to enteric bacterial infections, rational NEC-preventive strategies need incontestable safety profiles. Here we show in a clinically relevant animal model that FFT, as opposed to FMT, efficiently prevents NEC without any recognizable side effects. If translatable to preterm infants, this could lead to a change of practice and in turn a reduction in NEC burden.
Project description:Sequencing of 16S ribosomal RNA (rRNA) gene, which has improved the characterization of microbial community, has made it possible to detect a low level Helicobacter pylori (HP) sequences even in HP-negative subjects which were determined by a combination of conventional methods. This study was conducted to obtain a cutoff value for HP colonization in gastric mucosa biopsies and gastric juices by the pyrosequencing method. Corresponding author: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea (Tel., +82-31-787-7008; e-mail, nayoungkim49@empas.com). Microbial DNA from gastric mucosal samples [gastric antrum (n=63, mucosal biopsy), follow-up sample on gastric antrum (n=16, mucosal biopsy), and gastric body (n=18, mucosal biopsy)] and gastric juices (n=4, not mucosal biopsy) was amplified by nested PCR using universal bacterial primers, and the 16S rRNA genes were pyrosequenced.
Project description:Bacterial sepsis is associated with high morbidity and mortality in preterm infants. However, diagnosis of sepsis and identification of the causative agent remains challenging. Our aim was to determine genome-wide expression profiles of very low birth weight (VLBW) infants with and without bacterial sepsis and assess differences.
Project description:Over the course of milk digestion, native milk proteases and infant digestive proteases fragment intact proteins into peptides with potential bioactivity. This study investigated the release of peptides over three hours of gastric digestion in 14 preterm infant sample sets. The peptide content was extracted and analyzed from milk and gastric samples via Orbitrap tandem mass spectrometry. The relative ion intensity (abundance) and count of peptides in each sample were compared over time and between infants fed milk fortified with bovine milk fortifier and infants fed unfortified milk. Bioactivity of the identified peptides was predicted by sequence homology to known bioactive milk peptides. Both total and bioactive peptide abundance and count continuously increased over three hours of gastric digestion. After accounting for infant weight, length, and post-conceptual age, fortification of milk limited the release of peptides from human milk proteins. Peptides that survived further gastric digestion after their initial release were structurally more similar to bioactive peptides than non-surviving peptides. This work is the first to provide a comprehensive profile of milk peptides released during gastric digestion over time, which is an essential step in determining which peptides are most likely to be biologically relevant in the infant.
Project description:Unpublished single cell RNAseq data from pan-GI integration study from healthy adult donors (20-70 years old; stomach, duodenum, ileum) and control samples from preterm infants (23-31 PCW; small intestine and colon). Details for sample processing can be found in the manuscript.