Effects of Recto-colic Enemas of Butyrate on the Digestive Disorders of Very Low Birth Weight Preterms <1250 Grams

Clinical management of very low birth weight newborns (VLBW \<1250g) consists in several challenges to adapt immature physiological systems to extrauterine life. Advances in neonatal medicine for pulmonary and/or neurological and/or cardiovascular diseases have significantly improved outcomes of these children. However, the gastro-intestinal (GI) tract remains a major cause of morbidity due to 1. the immaturity of GI functions (prolonged ileus, bacterial overgrowth and translocation), 2. the complication of GI tract immaturity: intestinal perforation and enterocolitis necrotizing) 3. the need of a prolonged parenteral nutrition and its complications (central venous catheter infections, sepsis, electrolyte disturbances) but without generate a high proof level on this targeted population (\<1250g). The GI functions are progressively acquired during development and are largely sensitive to the environment, especially the intestinal luminal content. Indeed, probiotics and prebiotics have shown beneficial effects upon GI functions of newborns. One of the metabolite of the gut flora potentially involved is the butyrate. Butyrate is a short chain fatty acid produced in the colon by the microbiota (carbo-hydrates degradation). The colonic amount of butyrate increases gradually after birth. The beneficial effects of butyrate are related to its properties upon the epithelial barrier (anti-inflammatory, antioxidant, barrier repair) and upon the enteric nervous system (network of neurons and glial cells) that regulate GI functions and in particular colonic motility. To date, there is no clinical consensus to manage digestive disorders of VLBW. Several clinical studies have assessed the effects of prokinetic drugs, dietary supplements (probiotics, prebiotics) but without generate a high proof level on this targeted population. In this context, a recent study of our Research Unit (INSERM-CIC Mère-Enfant 004) has shown benefit effects of oral probiotics supplementation in child