Interventions shown to reduce systemic inflammation and improve epithelial regeneration of children with severe malnutrition
Treatments aimed at improving gut health in children with severe malnutrition can help reduce harmful inflammation in the body and blood vessels.
Researchers from the Blizard Institute, the Zvitambo Institute for Maternal and Child Health Research (Zimbabwe) and the Tropical Gastroenterology and Nutrition Group at the University of Zambia have found that treatments aimed at improving gut health in children with severe malnutrition can help reduce harmful inflammation in the body and blood vessels. These treatments also support the repair of the gut lining, which is crucial for absorbing nutrients and overall recovery after malnutrition.
In this paper, published in eBioMedicine and funded by Wellcome and MRC funding, the researchers performed analysis of tertiary outcomes from the phase II multi-centre TAME trial involving 122 children with Severe Acute Malnutrition (SAM) in Zambia and Zimbabwe. Within the TAME trial, one of four interventions aimed at treating gut dysfunction caused by malnutrition were administered for 14 days while children were in hospital. These were budesonide, N-acetylglucosamine, colostrum, or teduglutide, which were compared with standard-of-care. The children's plasma biomarkers of systemic and vascular inflammation were analysed. Researchers have rarely used advanced methods to study these kind of biomarkers that could provide more insights into the processes underlying malnutrition.
Both budesonide and colostrum appeared to reduce systemic inflammation, while children receiving colostrum showed better restoration of epithelial barrier function. N-acetylglucosamine also increased biomarkers of epithelial regeneration and circulating growth factors. The interventions showed positive effects on biomarkers of inflammation and epithelial regeneration, demonstrating an interdependence of systemic inflammation and enteropathy markers.
SAM is the most dangerous form of undernutrition, and children who are hospitalised with complications face a high risk of death. Researchers still do not fully understand the underlying causes of the disease – which is not simply due to insufficient food. Instead, SAM affects multiple body systems, leading to muscle loss, widespread inflammation, metabolism problems, and gut damage. There is an urgent need for new treatments to target these underlying issues and improve outcomes for affected children.
These findings suggest that treatments could help reduce harmful inflammation in the body and blood vessels of children with severe malnutrition, which can last for up to 48 weeks after they leave hospital. These treatments may also boost certain natural substances, called growth factors, that are linked to better recovery. The results show that when growth factor levels are higher, inflammation levels tend to be lower, suggesting a connection between the two.
Professor of Paediatric Infection and Immunology at Queen Mary, Honorary Consultant at Royal London Children’s Hospital and Director of the Zvitambo Institute for Maternal and Child Health Research, said: “When children are admitted to hospital with severe acute malnutrition, there is a high risk of dying or not recovering fully – even up to a year after leaving hospital.
“Since WHO guidelines were produced 25 years ago, there have been no major changes in treatment strategies for children who require hospital admission for severe acute malnutrition. We desperately need new strategies to help improve recovery from this high-risk condition. The TAME trial tested a new strategy – targeting the gut to improve healing of the damaged intestinal lining, so that children can better absorb nutrients and reduce the damaging effects of inflammation.
“These laboratory results suggest a step in the right direction – that two weeks of medicines targeting the gut shows signs of reducing the damaging effects of inflammation, and allowing restoration of tissues in children with malnutrition. The next step will be to test whether these promising laboratory results translate into better clinical recovery.”
More information
Research paper: Therapeutic interventions targeting enteropathy in severe acute malnutrition modulate systemic and vascular inflammation and epithelial regeneration. Sturgeon, Jonathan P. et al. eBioMedicine, Volume 111, 105478