Probiotics and prebiotics in neonatal necrotizing enterocolitis: New opportunities for translational research

Neonatal necrotizing enterocolitis (NEC) in premature infants has been recognized as a defined disease entity for at least four decades. Although survival has increased due to the advent of more sophisticated intensive care, incidence and long term health impacts due to NEC remain unchanged and no preventive therapy is currently available. Different probiotic strains of bacteria have been examined in their ability to prevent NEC with varied but encouraging results. Undigestable prebiotic sugars known to promote the growth of probiotic bacteria in the colon have been used in neonates with no clear benefit. The literature on NEC and probiotics is now cluttered with more reviews and meta-analyses than number of clinical trials. On the other hand, significant new information is available on microbiota and their impact on gut immunity. This review attempts to reiterate the risk factors of NEC and the pathogenesis of NEC with special reference to gut permeability. The reader is then introduced to gut microbiota, uniqueness and differences among probiotic strains, and how multiple resident flora talk to each other in the community setting in the human gut. After presenting a concise review of available clinical research results, the reader is challenged to question as to why no precise answer is available at present. Some modalities to examine the complex microflora and changes in the neonatal gut are then proposed including non-invasive methods and mathematical modeling. The review concludes by attracting the reader's attention to known immunomodulators of inflammation and injury. Justice to this review will be done only if the readers, clinical, and basic science investigators from multiple fields gather courage for a paradigm shift and embark on understanding the pathophysiology of the disease and attempt to discern the difference from equally preterm, equally vulnerable neonates that do not develop NEC. Learning about the developing microbiota in neonatal gut and its immunological impacts on the host in the face of many variables will provide a leap in our pursuit to select better, if not the best candidate probiotics, and put them to work against this stubborn disease that continues to take a toll on our precious neonates and the society.