The role of the supramucosal barrier in the pathogenesis of necrotizing enterocolitis

• Main Author: Carroll, Mr Daniel
• Published: University of Oxford 2005
• Subjects: 618.92
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491904

Necrotizing enterocolitis is a severe condition of the neonatal intestine characterised by intestinal inflammation and necrosis. Although many risk factors for this condition have been identified, the pathogenesis remains unclear. The identification of a large number of potential risk factors for this disease have led authors to speculate that the pathogenesis is likely to be multifactorial. • In this thesis we have examined the effects of necrotizing enterocolitis on the neonatal intestine, with particular reference to the supramucosal defence. In addition we have assayed the impact ofnecrotizing enterocolitis on the levels of faecal calprotectin levels in an attempt to develop a new tool for the early diagnosis ofnecrotizing enterocolitis. • These studies demonstrate that necrotizing enterocolitis is associated with changes in expression of components ofthe supramucosal barrier. In particular necrotizing enterocolitis appears to be associated with a reduction in expression ofTFF3. These changes were not seen in foetal material or in normal neonatal controls. There are also a number ofmore subtle alterations in gene expression demonstrable in necrotizing enterocolitis. However, it remains unclear as to whether these changes are as a result of tissue destruction and cellular damage, 2 Supplied by The British Library - 'The world's knowledge' fI or whether these changes pre-date the physiological insult responsible for the subsequent development ofnecrotizing enterocolitis. We have studied the expression of components ofthe supramucosal barrier in the developing gastrointestinal tract, to determine whether deficiencies in component of the supramucosal barrier as a result ofprematurity may represent an important component in the pathogenesis of necrotizing enterocolitis. The results of this work confirm the findings of other authors that both the mRNA signal and formed protein product of components of the supramucosal barrier are present in the developing human gastrointestinal tract from the end of the first trimester. It is unlikely that absolute failures ofproduction of individual components ofthe supramucosal barrier are solely responsible for the development of necrotizing enterocolitis. More subtle alterations may result in failure to produce of an effective supramucosal barrier, which may be important in contributing to the pathogenesis ofnecrotizing enterocolitis, but are beyond the scope ofthis experimental work. We have also demonstrated that necrotizing enterocolitis is associated with changes in faecal calprotectin levels in infants when compared to age-matched controls. This may prove an important observation, allowing for the utilization of faecal calprotectin as a diagnostic tool in the early diagnosis of necrotizing enterocolitis.