Although intestinal pathogens may cause NEC-like illness in animal models or occasional clinical outbreaks, they are not detected in most cases of classic NEC. 204NEC outbreaks have been associated with clusters of viral GI infections, but the clinical presentation may vary and often affect the large intestine. unlikely to cause disease by itself. Long term studies are needed to determine how therapeutic interventions on microbial communities may prevent the development of NEC. == Intro == Necrotizing enterocolitis (NEC) is the most common surgical emergency in premature infants, influencing approximately 7% of infants with less than 1500 g birth weights. 1Universally explained risk factors include prematurity, aberrant microbial colonization, and lack of human being milk feeding. 2NECs clinical presentation is nonspecific and can range from indicators limited to the gastrointestinal (GI) tract (eg, feeding intolerance, ileus, abdominal distention, hematochezia) to catastrophic illness with multiorgan failure (eg, lethargy, apnea, metabolic acidosis, shock, disseminated intravascular coagulopathy) and death. 3Since its first (-)-MK 801 maleate mention in the medical literature more than 150 years ago, NEC has stimulated intensive study in its cause; despite seminal discoveries of epidemiologic and molecular risk factors and pathways, the pathogenesis remains unclear. 4One reason for the lack in progress is inclusion of diseases closely resembling classic NEC as a complication of preterm delivery, such as spontaneous intestinal perforation (SIP), NEC in term infants, cow-milk intolerance, and viral enteritis. 5 The role of bacteria because significant contributors to NEC has been recognized since the first systematic descriptions of this disease. 6, 7Pneumatosis (-)-MK 801 maleate intestinalis and portal venous gas are pathognomonic radiographic signs of NEC8and thought to be caused by anaerobic bacteria, specifically clostridia. 9Gram-negative bacteria have (-)-MK 801 maleate been most frequently associated with NEC, and the epithelial receptor and innate immune sensor Toll-like receptor (TLR) 4 is elevated in the premature intestine and required for the development of experimental NEC. 10, 11NEC can occur in clusters, and seasonal outbreaks of virus-associated NEC cases have been reported. 12, 13, 14, 15, 16Here the authors attempted to summarize the (-)-MK 801 maleate main released data around the role of microbes in NEC. == Bacteria == Bacteria are clearly involved in the pathogenesis of NEC (Table 1); despite the paucity of randomized control trials to determine the optimal (-)-MK 801 maleate antimicrobial regimen in premature infants, treatment with intravenous broad-spectrum antibiotics remains a mainstay of the clinical management. 17, 18However, many open questions remain, including the role of specific bacterial overgrowth because the cause or the consequence of NEC, timing of bacterial colonization during fetal/neonatal development, and type of molecular interactions between diverse microbes and their host. 19Despite the large quantity of bacteria in the premature intestine early in life20and the clinical appearance of gram-negative sepsis, a positive blood culture is uncommon in infants with NEC. 21, 22This obtaining is surprising given the frequent growth of bacteria in peritoneal fluid. 23In 80 cases of NEC with intestinal perforation, Enterobacteriaceaewere present in the peritoneal fluid in 75% of cases, coagulase-negativeStaphylococci(CoNS) ATF3 in 14%, and anaerobes in 6%. 23Despite similar age at the time of intestinal perforation and similar mortality, the distribution of predominant organisms cultured from peritoneal fluid differed significantly between patients with NEC and SIP. Candidaspecies (44%) and CoNS (50%) dominated samples from 36 patients with SIP. 23Specific bacteria have been suggested as important contributing factors in NEC, 24, 25and NEC occurs typically after the first week post partum after the intestine continues to be colonized. In contrast, one study on human NEC samples using laser capture microdissection and subsequent sequencing combined with fluorescent in situ hybridization and bacterial rRNA-targeting oligonucleotide probes did not detect dominating potential pathogenic bacteria and suggested that NEC is a non-infectious syndrome. 9 == Table 1 . == Infectious reasons for NEC Abbreviations: MRSA, methicillin-resistantStaphylococcus aureus; VRE, vancomycin-resistant enterococci. Bacteria shape normal immune development including the development of T regulatory cells (Treg), which are critical for reducing inflammation-mediated injury. 26, 27, 28, 29Another example is recruitment of intestinal intraepithelial lymphocytes (IEL) after microbial colonization of germ-free mice. 30IEL.