Trial finds first potential drug for gut damage in malnutrition

A mother walking her daughter to school on a rural road

A trial of drugs to treat gut damage caused by malnutrition in children in Zambia and Zimbabwe has identified a potential drug that promoted intestinal healing.

The trial, funded by the Medical Research Council (MRC) through the Global Challenges Research Fund, is the first to identify a potential treatment that promotes healing of intestinal damage caused by severe acute malnutrition (SAM).

Each year 17 million children, mostly in Africa, experience SAM, and malnutrition underlies almost half of all child deaths globally.

No current treatments

Malnutrition also has long-term impacts on children, including growth stunting and long-term inhibition of neurodevelopmental potential, contributing to poor school performance.

For many children, providing improved nutrition alone may not avert these long-term consequences, because SAM causes damage to the small intestine, called enteropathy.

Malnutrition enteropathy reduces the ability of the intestine to absorb nutrients.

Studies have confirmed an association between such gut inflammation and mortality in complicated SAM.

No interventions to treat malnutrition enteropathy are currently available.

Four interventions trialled

This new trial of 125 children who had been hospitalised due to complications arising from SAM evaluated four interventions for malnutrition enteropathy in a multi-centre phase two multi-arm trial in Zambia and Zimbabwe.

The study found a drug called teduglutide enhanced the healing of mucosal membranes and reduced inflammation in the gut in children affected by the long-team health consequences of a period of malnutrition.

The research gathered the first evidence in three decades that confirmed that treating malnutrition enteropathy can reduce intestinal damage amongst children experiencing the effects of complicated SAM.

Reducing complications

Paul Kelly, Professor of Tropical Gastroenterology at Queen Mary University of London, who led the study, said:

Severe acute malnutrition carries unacceptable mortality, particularly if accompanied by infection or medical complications, including enteropathy.

We have shown that a short course of therapy added to standard care, aimed at restoring mucosal integrity, can reduce these complications, and we look forward to examining these treatments further in phase three clinical trials.

Biologically plausible new treatment paradigm

The study found a biologically plausible new treatment paradigm, where intestinal damage drives systemic inflammation, contributing to stunting and developmental impairment, and increasing mortality.

Researchers identified that a short course of treatment to restore mucosal integrity in the gut can ameliorate underlying pathogenic pathways when added to standard care.

Teduglutide is already widely used to treat intestinal failure, a clinical syndrome with features in common with the more severe cases of SAM.

Other potential therapies

The three other therapies tested in the trial showed smaller effects on markers of intestinal healing.

The drug budesonide reduced the systemic inflammatory marker C-reactive protein, which is a predictor of infant mortality.

Bovine colostrum and N-acetyl glucosamine also reduced inflammation.

In addition, colostrum increased mucosal regeneration and N- acetyl glucosamine reduced diarrhoea.

Promising strategy

Further clinical trials are needed to determine if such treatments, particularly teduglutide, can reduce the poor long-term outcomes and death rates in children with SAM.

However, this trial demonstrates that the treatments are likely to be safe, and confirms mucosal healing as a promising strategy in severe malnutrition.

Improving health and wellbeing

Dr Jess Boname, Acting Head of Population and Systems Medicine at MRC, said:

This study was funded by the Medical Research Council to address the tragedy that nearly half of deaths among children under five worldwide are linked to undernutrition.

While the UK and many developing countries are suffering from an obesity crisis, undernutrition still causes a high death rate in children under five, mostly in low- and middle-income countries.

We hope that this study will lead to effective treatments that will improve the health and wellbeing of children suffering from acute malnutrition and provide lasting benefits for the whole community.

Further information

‘Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial’ is published in Nature Communications.

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