Necrotizing Enterocolitis: Intraluminal Biochemistry in Human Neonates and a Rabbit Model

Abstract

NS, normal salineThe etiology of necrotizing enterocolitis has remained elusive despite numerous theories. It occurs primarily in infants born prior to 34 wk gestation (1, 2). These infants have intestinal ileus, abdominal distention, and bloody stools. Roentgenographic examination of the abdomen reveals distended loops of bowel and in the classic presentation, pneumatosis intestinalis (1, 3). Often the clinical course is fulminant with hemorrhagic necrosis of the bowel, metabolic acidosis, respiratory insufficiency, and sepsis progressing to death (4).While numerous epidemiologic associations have been suggested, only a few consistent underlying factors have been identified. These include prematurity (1, 5 ) , enteral feeding (6, 7), and enteric bacteria (3,8). Reports have also noted a clustering of cases suggesting an infectious agent, but investigations to define a causative bacteria or virus have as yet been inconclusive (6, 9). Numerous investigators have implicated compromised intestinal vascular supply resulting from birth asphyxia, respiratory distress, hypotension, and the use of umbilical arterial catheters. Unfortunately, recent studies have shown that many of these epidemiologic associations cannot be confirmed with careful analysis ( 10).Although prevailing theories suggest a primary vascular insult, many preterm infants seem to have an abrupt onset of necrotizing enterocolitis with no obvious predisposing factors. We ex- amined the intestinal contents of preterm infants with severe necrotizing enterocolitis. The low intraluminal pH and high protein content in the intestines of these neonates led us to examine the variables of pH and protein in a rabbit intestinal loop model. MATERIALS A N D METHODSNronute.~. We obtained the intestinal contents at or adjacent to the site of perforation or necrosis in 17 infants requiring surgical removal of the intestine for advanced necrotizing enterocolitis. The intestinal contents were analyzed for blood, pH, carbohydrate, protein, and bacteria. The presence of blood was confirmed by the guaiac test. The presence of carbohydra1.e available for bacterial fermentation was initially determined by reducing substances and then quantitated by measurement of glucose after incubation with lactase (Nutritional Biochemicals). The protein content was determined by the Lowry technique and the primary protein present was estimated by acrylamide gel electrophoresis (1 1). The contents were cultured for aerobic and anaerobic organisms by routine bacteriologic techniques. The predominant lactose fermenting aerobic organism was isolated on MacConkey media.Rubhit model. A modification of the rabbit intestinal loop model of Kasai and Burrows provided a means for examining the variables of intraluminal pH and protein (12, 13). Sixteen New Zealand white weanling, 3-wk-old-male rabbits were fasted for 8 h. Blood from a cross-match compatible donor rabbit was drawn by syringe and the red blood cells were labeled with Chromiums1. A I-ml aliquot of blood was then injected into each rabb...

Short-Chain Fatty Acids Induce Colonic Mucosal Injury in Rats with Various Postnatal Ages

“…Levels of SCFAs in the distal ileum may also increase from backward reflux across the ileocecal valve or as a result of local bacterial overgrowth. High concentrations of SCFAs can significantly lower the pH in the bowel (15,16).…”

Use of pigs as a potential model for research into dietary modulation of the human gut microbiota

“…Obviously, MCFA can influence microbial ecology in the stomach and bacterial metabolites in the small intestine (166) . Interestingly, the development of NEC is assumed to be linked to higher levels of SCFA in the premature human intestine (167) , and the administration of SCFA can cause mucosal injury in rats (168) . Moreover, Cilieborg et al (155) determined significantly higher concentrations of acetate in the stomach, and significantly more acetate and butyrate in the colon of piglets with NEC compared with healthy animals.…”

Development of Gastrointestinal Function: Risk Factors for Necrotizing Enterocolitis

“…Of these, inflammation of the bowel is by far the most common, accounting for 85% to 90% of all cases. 22,27 There are several clinical risk factors that have been identified. These include decreased stools following increased feedings.…”

“…Consequently the preterm infant develops gaseous abdominal distention and, due to the irritation of the short chain fatty acids, some loose watery stools. 22 Protein digestion and absorption can first be detected with proteolytic enzymes developed between 20 and 26 weeks of gestation. 8,23 The amniotic fluid proteins swallowed by the preterm infant are very similar to the whey proteins found in human milk contributing to the evolution of these enzymes.…”

“…21 Any carbohydrate that is not digested and absorbed becomes available to the bacteria colonizing the colon. 22 These bacteria will then readily ferment the carbohydrate yielding several gases, hydrogen and carbon dioxide and a series of short chain fatty acids to include lactic, acetic, butyric, propionic, and formic acids depending on the specific organism. Consequently the preterm infant develops gaseous abdominal distention and, due to the irritation of the short chain fatty acids, some loose watery stools.…”