Necrotizing enterocolitis: treatment based on staging criteria.

The gastrointestinal tract is a complex ecosystem that associates a resident microbiota and cells of various phenotypes lining the epithelial wall expressing complex metabolic activities. The resident microbiota in the digestive tract is a heterogeneous microbial ecosystem containing up to 1×1014 colony-forming units (CFUs) of bacteria. The intestinal microbiota plays an important role in normal gut function and maintaining host health. The host is protected from attack by potentially harmful microbial microorganisms by the physical and chemical barriers created by the gastrointestinal epithelium. The cells lining the gastrointestinal epithelium and the resident microbiota are two partners that properly and/or synergistically function to promote an efficient host system of defence. The gastrointestinal cells that make up the epithelium, provide a physical barrier that protects the host against the unwanted intrusion of microorganisms into the gastrointestinal microbiota, and against the penetration of harmful microorganisms which usurp the cellular molecules and signalling pathways of the host to become pathogenic. One of the basic physiological functions of the resident microbiota is that it functions as a microbial barrier against microbial pathogens. The mechanisms by which the species of the microbiota exert this barrier effect remain largely to be determined. There is increasing evidence that lactobacilli and bifidobacteria, which inhabit the gastrointestinal microbiota, develop antimicrobial activities that participate in the host's gastrointestinal system of defence. The objective of this review is to analyze the in vitro and in vivo experimental and clinical studies in which the antimicrobial activities of selected lactobacilli and bifidobacteria strains have been documented.

Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens

Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.

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Hirschsprung disease, associated syndromes and genetics: a review

https://www.gastrojournal.org/article/S0016-5085(04)00456-1/pdf

Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics

The gastrointestinal epithelium forms the boundary between the body and external environment. It effectively provides a selective permeable barrier that limits the permeation of luminal noxious molecules, such as pathogens, toxins, and antigens, while allowing the appropriate absorption of nutrients and water. This selective permeable barrier is achieved by intercellular tight junction (TJ) structures, which regulate paracellular permeability. Disruption of the intestinal TJ barrier, followed by permeation of luminal noxious molecules, induces a perturbation of the mucosal immune system and inflammation, and can act as a trigger for the development of intestinal and systemic diseases. In this context, much effort has been taken to understand the roles of extracellular factors, including cytokines, pathogens, and food factors, for the regulation of the intestinal TJ barrier. Here, I discuss the regulation of the intestinal TJ barrier together with its implications for the pathogenesis of diseases.

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Regulation of intestinal epithelial permeability by tight junctions

Enteral probiotics such as Lactobacillus casei GG (LGG) have been used in the treatment of a variety of intestinal disorders in infants and children, including diarrhea, malabsorption, and Clostridium difficile colitis. Previous studies have identified the gene locus for mucin (MUC-2) and its expression in Caco-2 cells. Others have demonstrated that mucin, located on the surface of the intestinal epithelium, inhibits bacterial translocation (BT). We previously demonstrated that both mucin and the probiotic bacterium LGG have an inhibitory effect on BT in both an in-vitro Caco-2 cell model and a neonatal rabbit model. We hypothesized that the decline in BT by LGG is mediated by up-regulation of epithelial MUC-2. Human enterocyte Caco-2 cells were grown to confluence and incubated at 37 � C with either medium (control group) or 10 4 or 10 8 LGG for 180 min. Non- adherent LGG was washed away. Caco-2 cells were then lysed, purified, and quantified for MUC-2 protein and mRNA. The addition of LGG to the enterocyte mono- layer surface resulted in significantly (P < 0.05) in- creased MUC-2 expression compared to the untreated monolayers. Protein densities for MUC-2 significantly (P < 0.05) increased with LGG. Density (expressed as ratio to control group) was 8.6 ± 1.3 in the low-dose group (10 4 LGG) and 15.6 ± 2.3 in the high-dose group (10 8 LGG). LGG may thus bind to specific receptor sites on the enterocyte and stimulate the up-regulation of MUC-2, resulting in increased inhibition of BT.

/pdf/probiotics-up-regulate-muc-2-mucin-gene-expression-in-a-caco-25v322f1u6.pdf

Probiotics up-regulate MUC-2 mucin gene expression in a Caco-2 cell-culture model.

Delayed Versus Immediate Surgery In Acute Appendicitis: Do We Need to Operate During the Night?

The risk of developmental of total parenteral nutrition (TPN)-associated cholestatic jaundice in neonates receiving intravenous hyperalimentation is high. Numerous factors have been cited as contributing to TPN cholestasis; however, the exact etiology remains obscure. This retrospective study was undertaken in order to identify any factors which might contribute to this syndrome. The hospital records of 172 neonates requiring TPN for a minimum of 1 week were reviewed. In addition, a subgroup of 32 infants requiring TPN for a minimum of 7 weeks was also examined. Cholestasis was defined as a direct serum bilirubin greater than 2.0 mg/dl during the course of TPN therapy. Significant factors for the development of cholestasis in both groups (n = 172, n = 32) included: number of operations (2.56 vs. 1.08, p = 0.0000), the number of days the patients received antibiotics (40.3 vs 12.9, p = 0.0000), and delayed start of enteral feedings (33.8 vs 14.1, p = 0.0000). Fifteen of the 32 patients who received TPN for at least 7 weeks did not develop cholestasis. In this subgroup (n = 32), there were no differences in birth weight, gestational age, days from birth to the start of TPN, or respiratory distress between those who developed cholestasis and those who remained anicteric. In contrast, there were significant differences between the cholestasis and noncholestasis groups in number of operations (13 vs 6, p = 0.0407), and days until enteral feedings were started (33.1 vs 18.9, p = 0.0289). This study suggests that the factor(s) contributing to the development of TPN-associated cholestasis are likely multifactorial. There appears to be a direct correlation between increasing severity of cholestatic jaundice and duration of TPN. This review does add a new parameter to the various causative factors suggested, namely the number of operative procedures. This new variable could be related to the stress of surgery itself or to the repeated administration of anesthetic agents.

/pdf/an-analysis-of-factors-contributing-to-the-development-of-2zgzcvedlg.pdf

Robert A. Drongowski

Papers

Probiotics up-regulate MUC-2 mucin gene expression in a Caco-2 cell-culture model.

Delayed Versus Immediate Surgery In Acute Appendicitis: Do We Need to Operate During the Night?

An Analysis of Factors Contributing to the Development of Total Parenteral Nutrition-Induced Cholestasis

Lack of enteral nutrition—effects on the intestinal immune system

Acute kidney injury in congenital diaphragmatic hernia requiring extracorporeal life support: an insidious problem