Antibiotics Increase Gut Metabolism and Antioxidant Proteins and Decrease Acute Phase Response and Necrotizing Enterocolitis in Preterm Neonates

Background: The appropriate use of antibiotics for preterm infants, which are highly susceptible to develop necrotizing enterocolitis (NEC), is not clear. While antibiotic therapy is commonly used in neonates with NEC symptoms and sepsis, it remains unknown how antibiotics may affect the intestine and NEC sensitivity. We hypothesized that broad-spectrum antibiotics, given immediately after preterm birth, would reduce NEC sensitivity and support intestinal protective mechanisms. Methodology/Principal Findings: Preterm pigs were treated with antibiotics for 5 d (oral and systemic doses of gentamycin, ampicillin and metrodinazole; AB group) and compared with untreated pigs. Only the untreated pigs showed evidence of NEC lesions and reduced digestive function, as indicated by lowered villus height and activity of brush border enzymes. In addition, 53 intestinal and 22 plasma proteins differed in expression between AB and untreated pigs. AB treatment increased the abundance of intestinal proteins related to carbohydrate and protein metabolism, actin filaments, iron homeostasis and antioxidants. Further, heat shock proteins and the complement system were affected suggesting that all these proteins were involved in the colonization-dependent early onset of NEC. In plasma, acute phase proteins (haptoglobin, complement proteins) decreased, while albumin, cleaved C3, ficolin and transferrin increased. Conclusions/Significance: Depressed bacterial colonization following AB treatment increases mucosal integrity and reduces bacteria-associated inflammatory responses in preterm neonates. The plasma proteins C3, ficolin, and transferrin are potential biomarkers of the colonization-dependent NEC progression in preterm neonates. © 2012 Jiang et al.published_or_final_versio

Early antibiotic use and incidence of necrotising enterocolitis in very preterm infants: a protocol for a UK based observational study using routinely recorded data

Introduction Necrotising enterocolitis (NEC) remains a major contributor to preterm mortality and morbidity. Prolonged duration of antibiotic therapy after delivery is associated with later NEC development but recent evidence suggests that absence of antibiotic treatment after delivery may also increase NEC risk. We will explore this controversy using a large pre-existing dataset of preterm infants in the UK. Methods and analysis: This is a retrospective cohort study using data from UK National Neonatal Research Database (NNRD) for infants born 1 January 2012 to 31 December 2020. Eligible infants will be <32 weeks gestation, alive on day 3. Primary outcome is development of severe NEC, compared in infants receiving early antibiotics (days 1–2 after birth) and those not. Subgroup analysis on duration of early antibiotic exposure will also occur. Secondary outcomes are: late onset sepsis, total antibiotic use, predischarge mortality, retinopathy of prematurity, intraventricular haemorrhage, bronchopulmonary dysplasia, focal intestinal perforation and any abdominal surgery. To address competing risks, incidence of death before day 7, 14 and 28 will be analysed. We will perform logistic regression and propensity score matched analyses. Statistical analyses will be guided by NEC risk factors, exposures and outcome presented in a causal diagram. These covariates include but are not limited to gestational age, birth weight, small for gestational age, sex, ethnicity, delivery mode, delivery without labour, Apgar score, early feeding and probiotic use. Sensitivity analyses of alternate NEC definitions, specific antibiotics and time of initiation will occur. Ethics and dissemination: We will use deidentified data from NNRD, which holds permissions for the original data, from which parents can opt out and seek study-specific research ethics approval. The results will help to determine optimal use of early antibiotics for very preterm infants. Implications: This data will help optimise early antibiotic use in preterm infants. Trial registration number: ISRCTN55101779

IL-1α Mediated Chorioamnionitis Induces Depletion of FoxP3+ Cells and Ileal Inflammation in the Ovine Fetal Gut

Endotoxin induced chorioamnionitis increases IL-1 and provokes an inflammatory response in the fetal ileum that interferes with intestinal maturation. In the present study, we tested in an ovine chorioamnionitis model whether IL-1 is a major cytokine driving the inflammatory response in the fetal ileum.Sheep bearing singleton fetuses received a single intraamniotic injection of recombinant ovine IL-1α at 7, 3 or 1 d before caesarian delivery at 125 days gestational age (term = 150 days).3 and 7 d after IL-1α administration, intestinal mRNA levels for IL-4, IL-10, IFN-γ and TNF-α were strongly elevated. Numbers of CD3+ and CD4+ T-lymphocytes and myeloidperoxidase+ cells were increased whereas FoxP3+ T-cells were detected at low frequency. This increased proinflammatory state was associated with ileal mucosal barrier loss as demonstrated by decreased levels of the intestinal fatty acid binding protein and disruption of the tight junctional protein ZO-1.Intraamniotic IL-1α causes an acute detrimental inflammatory response in the ileum, suggesting that induction of IL-1 is a critical element in the pathophysiological effects of endotoxin induced chorioamnionitis. A disturbed balance between T-effector and FoxP3+ cells may contribute to this process

Uptake of Colostral Immunoglobulins by the Compromised Newborn Farm Animal

Neonatal mortality is very high in farm animals (~10%) and disease resistance is greatly influenced by an adequate passive immunisation just after birth. In piglets, foals, calves and lambs, the intestinal absorption of immunoglobulins from their mother's colostrum occurs mainly by a non-specific endocytosis of macromolecules, but the details of the absorption process, and the mechanisms regulating its cessation after 1–2 days of colostrum exposure, remain poorly understood. In both normal and 'compromised' (premature, growth-retarded, hypoxic, lethargic) newborn farm animals, the intestinal capacity to absorb macromolecules is influenced by both diet- and animal-related factors. Thus, macromolecule uptake is severely reduced in response to premature birth and when macromolecules are to be absorbed from diets other than species-specific colostrum. On the other hand, fetal growth retardation, in vitro embryo production, or a stressful birth process are unlikely to reduce the ability of the intestine to absorb immunoglobulins from colostrum. More knowledge about the diet- and animal-related factors affecting intestinal immunoglobulin uptake will improve the clinical care of 'compromised' newborn farm animals. The present text gives a brief introduction to the process of intestinal immunoglobulin absorption in large farm animals and describe some recent results from the author's own studies in pigs, calves and lambs.</p

Ludovic Falaix, Des vagues et des hommes. La glisse au cœur des résistances et contestations face à l’institutionnalisation des territoires du surf en Aquitaine

En s’interrogeant sur la manière dont les surfeurs habitent l’espace-vague, cette thèse s’attache à construire comme énigme de recherche l’observation de leurs résistances et contestations face à l’institutionnalisation de leurs territoires de pratique. Elle mobilise l’habiter, entendu comme un nouveau concept riche en controverses scientifiques (Frelat-Kahn et Lazzarotti, 2012 ; Berque, de Biase et Bonnin, 2008 ; Goetz, 2011 ; Paquot, Lussault et Younès, 2007), afin d’élaborer une géographie..

The prenatal porcine intestine has low transforming growth factor-beta ligand and receptor density and shows reduced trophic response to enteral diets

Transforming growth factor-beta (TGF-β) plays a role in enterocyte proliferation control, cell differentiation, and immune regulation via binding to specific TGF-β receptors (TGF-β R) in the intestinal epithelium. Endogenous TGF-β production is low in the intestine during the perinatal period, but some exogenous TGF-β ligands are supplied by amniotic fluid intake in the fetus and by colostrum ingestion in the neonate. It is not clear, however, whether luminal TGF-β receptors are present and functional at this critical time. We studied intestinal TGF-β receptors by immunohistochemistry during the last 20% of gestation in pigs and in chronically catheterized fetuses following exposure to colostrum, milk, and amniotic fluid (control). In fetal pigs, the TGF-β Rs were predominantly localized to the crypt epithelium, but staining intensity increased markedly just before term and shifted to the villous epithelium in newborn pigs, concurrently with marked increases in villous heights and crypt depths (+100-200%, P < 0.05). In contrast to previous observations in term newborn pigs, fetal pigs did not show any milk-induced change in TGF-β receptor densities or localization, although a moderate increase in villous height was observed, relative to control (+25-50%, P < 0.05). We conclude that intestinal TGF-β receptor density and localization are immature and unresponsive to TGF-β containing milk diets in prenatal pigs. Immaturity of TGF-β-mediated immune regulation may play a role in the increased sensitivity of preterm neonates to diet-induced intestinal inflammatory disorders. Copyright © 2009 the American Physiological Society.link_to_OA_fulltex