NEC is a common and severe gastrointestinal disease in pre-term infants, with mortality and morbidity more likely the lower the gestational age and birth weight are. Apart from gastrointestinal complications, NEC can also cause neurodevelopmental impairment.
Recent studies have found that gut microbiome dysbiosis has a crucial role in the pathogenesis of NEC.
This has led researchers to explore the role of probiotics in helping to reduce the morbidity and mortality rates of NEC in pre-term infants, but outcomes regarding the safety and efficacy of probiotics in clinical applications have so far been inconclusive.
Researchers at China's Peking University sought to review the association of gut microbiome development with NEC in pre-term infants, as well as the potential preventive impact of probiotics on the disease.
Facilitating factors
They reported that factors such as Caesarean section (C-section) birth, artificial feeding, perinatal period and postnatal antibiotics in premature infants tended to delay the colonisation of intestinal flora, making intestinal micro-ecological disorders more likely and increasing the risk of NEC.
Previous studies had found that the proportion of proteobacteria (bacteria that include a wide range of pathogens and are associated with inflammation) increased before the onset of NEC.
At the same time, the proportion of Clostridium has been found to be higher in infants with early-onset NEC, while in infants with late-onset NEC, the proportions of Shigella and Escherichia tend to be higher.
These findings suggest that intestinal flora dysregulation usually precedes the onset of NEC. As such, the researchers wrote that "monitoring changes in intestinal microecology can predict the severity of NEC".
However, while some research has reported that gut microbial diversity in infants with NEC tends to be markedly lower than in healthy infants, other studies have found no statistically significant differences in intestinal flora composition of infants with NEC and healthy infants.
The gut-brain axis?
Recent studies have also found a link between intestinal flora imbalance and complications in the nervous system. NEC has been found to affect premature infants' cognition and language, as well as their motor development.
There have been disputes as to the best approach to treat NEC-induced neurodevelopmental issues, with some experts advocating surgical procedures, while others prefer more conservative treatment methods.
The review stated: "The results suggest that there is a need to monitor the poor prognosis of the nervous system in children with NEC.
"Because there is still a lack of literature on the correlation between intestinal flora disorders and the severity of NEC-related neurological complications, whether the flora disorder or the NEC lesion itself causes a poor prognosis of the nervous system remains to be further studied."
Probiotics: Pro or con?
The review also stated that a meta-analysis had found that the prophylactic use of probiotics in pre-term infants, especially when multiple probiotics were combined, could significantly lower the incidence of NEC and its mortality rate.
However, it also said there was no noticeable difference in neurodevelopment between infants with NEC and healthy infants after the administration of prophylactic probiotics, suggesting probiotics do not improve the development of the nervous system in pre-term infants.
The researchers added that the effectiveness of probiotics in clinical applications could be influenced by several factors, including infant birth weight, and probiotics' composition components and strain-specific effects.
The fact that probiotics are living microorganisms also add to the uncertainty of their clinical application. As intestinal development in pre-term infants is still immature, safety hazards are more likely when they are given probiotics. While uncommon, there have been cases of septicaemia reported among premature infants after they were given probiotics.
Another potential safety hazard in the administration of probiotics is the transmission of resistance genes. Some premature infants are exposed to antibiotics after birth, which may result in resistance to probiotic treatment.
Probiotics can also transfer drug-resistant genes to intestinal pathogenic bacteria, causing this bacteria to develop drug resistance, thereby severely affecting physical health.
However, probiotics' possible adverse effects on the immune system need further research.
The researchers concluded: "NEC is a common severe gastrointestinal emergency in premature infants, which affects the long-term development of the nervous system in premature infants; intestinal microecological disorders play an important role in its pathogenesis.
"At present, it has been confirmed that intestinal flora imbalance precedes NEC, but it is affected by factors such as individual differences, sample size, and bacterial taxonomic units. Whether intestinal flora changes can predict the severity of NEC needs further trial and verification.
"The role of microecological preparations in the prevention of NEC in premature infants has attracted widespread attention. Most studies have confirmed the effectiveness and safety of probiotics. However, there is currently no uniform optimal standard for the application of probiotics.
"Probiotics are improving. The role of long-term neurological prognosis is also unclear and remains to be further validated by large-sample multi-centre randomised controlled trials."
Source: Chinese Journal of Contemporary Pediatrics
http://dx.doi.org/10.7499/j.issn.1008-8830.2018.08.015
"A review of the relationship between gut microbiome and necrotizing enterocolitis in preterm infants"
Authors: Ma Yuanpei, Ma Jing Yue