**13. Future directions**

NEC remains a major unsolved medical challenge for which no specific therapy exists. Recent research is concentrated on the role of TLR4 signaling within the intestinal epithelium and intestinal stem cells and modulation of the genetics and

intestinal microbiome. Fecal microbiota transplantation (FMT) has been shown to reverse the severity of experimental necrotizing enterocolitis (NEC) via oxidative stress modulation [65]. FMT decreases the extent of TLR4-mediated pro-inflammatory signaling through TLR9 in the intestinal mucosa tissue. FMT also suppresses intestinal apoptosis and bacterial translocation across the intestinal barrier, which is accompanied by decreased inflammatory cytokine levels, altered bacterial microbiota, and regulated lymphocyte proportions. Research is needed to determine if the use of biomarkers along with specific clinical-biochemical indicators could lead to earlier intervention with modalities, such as peritoneal drainage or laparotomy that might decrease the severity of the disease process, thereby improving the long-term neurodevelopmental and growth outcomes. Improved care of short bowel syndrome with new surgical and medical approaches are additional subject for investigation. Tissue engineering techniques and techniques involving intestinal stem cells may represent unique, novel strategies for intestinal failure after severe NEC in the future.
