Postnatal maturation of the intestinal barrier occurs coincident with increasing enteral feeding. Normal intestinal bacterial colonization is established once enteral feeding is achieved. Colonization of intestinal microflora plays a vital role in the regulation and maintenance of intestinal barrier function. As the important end products of intestinal microbial fermentation of mainly undigested dietary carbohydrates in the intestinal lumen, short chain fatty acids (SCFAs) may mediate the regulatory effect of normal intestinal microflora on intestinal barrier function, especially the colonic mucosal barrier. During physiological conditions, the production of SCFAs in the bowel is very important for energy salvage and crucial for gastrointestinal adaptation and maturation. Multiple mechanisms may be involved in the regulation of the intestinal barrier by SCFAs. It is also possible that, excessive concentrations of SCFAs may be toxic and cause disruption of the intestinal barrier. Once the intestinal barrier is disrupted, the inflammatory cascade may be activated, which can induce further injury to the intestinal mucosa. Therefore it has been hypothesized that overproduction/accumulation of SCFAs in the intestinal lumen may play a pivotal role in the pathogenesis of neonatal necrotizing enterocolitis (NEC). While we may use probiotics for the prophylaxis of NEC in premature infants, we should be very cautious when considering the use of oligosaccharides (as prebiotics) in formulas for premature infants.