In a comprehensive study, researchers investigated the intestinal mucosal barrier in neonatal piglets, identifying important dynamics and a potential new therapy for preterm human infants, who are highly vulnerable to severe health complications. The research highlights the critical role of the intestinal mucosal barrier in human health as the primary defence against pathogens.
Every year, about 15 million children globally are born prematurely, increasing their risk of developing serious health problems, including increasing their vulnerability to serious complications such as necrotising enterocolitis, in which inflammation of the intestine enables bacterial invasion, causing cellular damage and death and necrosis of the colon.
“Half the infants who develop necrotising enterocolitis die, and it is a main cause of death among preterm infants. Treatment options are limited, with the primary interventions including administering antibiotics or removing the infected parts of the intestine, which can leave the children with short-bowel syndrome with lifelong complications. With our new study, we aimed to understand and perhaps improve treatment,” explains Stine Rønholt, Assistant Professor, LEO Foundation Center for Cutaneous Drug Delivery, University of Copenhagen, Denmark.
Barrier had clearly developed
The urgent need for more effective treatment options has led researchers to work intensively on developing new treatment strategies to improve survival for these vulnerable newborns. To understand the underlying mechanisms, Stine Rønholt and researchers from the Department of Pharmacy and the Nano-Science Center collaborated with the Department of Veterinary and Animal Sciences at the University of Copenhagen.
“The Department of Veterinary and Animal Sciences has developed models based on preterm piglets, which we used to investigate necrotising enterocolitis, which especially affects human infants born before gestational week 27. We aimed to understand the biological processes behind the sudden and violent inflammation of the intestine and to identify possible treatment methods,” she adds.
The study revealed that the intestinal mucosal barrier had clearly developed in preterm piglets, improving the structure of the mucosa and reducing its permeability compared with the mucosa of full-term piglets.
“Remarkably, we found that necrotising enterocolitis was associated with increased permeability of pathogens, which shows that the necrotising enterocolitis is directly linked with the intestinal mucosal barrier,” says Stine Rønholt.
Similarities in mucus function
The researchers focused on the development of the intestinal mucosal barrier in both full-term and preterm piglets, providing a relevant model for human infants because of similar physiology.
“Preterm piglets are the best animal model that can mimic necrotising enterocolitis and susceptibility to infection among preterm human infants. The immature systemic immune system of newborn piglets is very similar to that of preterm infants,” explains Stine Rønholt.
In addition, the mucus from pig intestines and the mucus from human intestines are similar in structure and function, furthering the relevance of using preterm piglets as a model.
“We also investigated whether the method of administration itself, either orally via a tube or directly orally, affects the intestinal mucosal barrier, which also led to important observations about how these differences can actually affect the development of the barrier,” says Stine Rønholt.
Potential candidate for future therapy
Much of the study involved administering sodium decanoate, a medium-chain fatty acid present in milk, which has been shown to have potential in treatment for intestinal diseases. It is also similar to sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC), an agent used in drugs to promote the transport of substances across the intestinal mucosal barrier.
“Interestingly, sodium decanoate had the opposite effect of what we expected. Sodium decanoate had varying effects on mucosal diffusivity depending on the health status and maturity of the animals. This opens up new perspectives in understanding the biology of the intestinal mucosal barrier and its therapeutic potential, indicating that the sodium decanoate could be a potential candidate for future therapies to support the health of gut bacteria,” explains Stine Rønholt.
The research improves understanding of the complex mechanisms that regulate the function of the intestinal mucosal barrier and how it responds to disease. The insight into the barrier’s dynamics and response to interventions can potentially lead to the development of targeted treatment strategies that are essential to promote the gut health of neonatal infants, especially those most vulnerable because they are born preterm.
“Our results emphasise the need to develop targeted treatment strategies that consider both the maturity and health status of neonatal infants. By carefully understanding how various therapeutic interventions affect the intestinal mucosal barrier, we can offer more effective and safer treatments to the most vulnerable patients – preterm infants,” concludes Stine Rønholt.
“Neonatal intestinal mucus barrier changes in response to maturity, inflammation, and sodium decanoate supplementation” has been published in Scientific Reports. The Lundbeck Foundation and the Novo Nordisk Foundation supported the study.
