First New Analysis in 3 Decades Identifies Which Treatments for the Long-Term Effects of Malnutrition Could Help Reduce Mortality and Poor Health Outcomes for Children

A comparison of treatments for malnutrition enteropathy, caused by severe acute malnutrition (SAM), has found evidence supporting the use of treatments to enhance the healing of mucosal membranes and reduce inflammation in the gut to improve the outcomes of children affected by long-team health consequences of a period of malnutrition. 

The Therapeutic Approaches to Malnutrition Enteropathy (TAME), led by researchers from Queen Mary University of London, evaluated four interventions for malnutrition enteropathy in a multi-centre phase II multi-arm trial in Zambia and Zimbabwe. No interventions for malnutrition enteropathy are currently available. The research gathered the first evidence in three decades which confirmed that treating malnutrition enteropathy can reduce intestinal damage amongst children experiencing the effects of complicated SAM.  

The study of 125 children who had been hospitalised due to complications arising from SAM 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. 

Researchers found that GLP-2 agonists such as Teduglutide enhances mucosal healing in children with SAM. None of the other interventions studied showed any significantly differences compared to standard care, however budesonide was also shown to reduce the systemic inflammatory marker C-reactive protein (CRP), 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. Further clinical trials are needed, but the TAME trial demonstrates that both treatments are likely to be safe, and confirms mucosal healing as a promising strategy in severe malnutrition. 

Paul Kelly, Professor of Tropical Gastroenterology at Queen Mary University of London, said: ‘Severe Acute Malnutrition (SAM) 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 III clinical trials.’ 

Dr Jess Boname, Acting Head of Population and Systems Medicine at the Medical Research Council, 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.” 

Each year 17 million children, mostly in Africa, experience SAM, and malnutrition underlies almost half of all child deaths globally. Studies have confirmed the very high frequency of in resource poor countries and an association between such gut inflammation and mortality in complicated SAM. 

NOTES TO EDITORS   

Peer-reviewed | Randomised Controlled Trial | People 

Contact:   

Honey Lucas 

Faculty Communications Officer – Medicine and Dentistry 

Queen Mary University of London 

Email: h.lucas@qmul.ac.uk or press@qmul.ac.uk

Paper details:   

M.P. Kelly et al. “Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial.” Published in Nature Communications.

DOI: 10.1038/s41467-024-45528-0 

Available after publication at: https://www.nature.com/articles/s41467-024-45528-0

Under strict embargo until 10am UK time Wednesday 17 April 2024. 

A copy of the paper is available upon request. 

Funding information:  

Conflicts of Interest Disclosures: Raymond J. Playford was previously an external consultant to Colostrum UK which provided the bovine colostrum used in these studies. Raymond J. Playford has also been an external consultant to Sterling Technology (USA) and an employee of Pantheryx Inc (USA) who produce and distribute bovine colostrum. There was no bovine colostrum company involvement in the production of this article or editing of its content. Susan Hill has had funding for teduglutide studies and lectured and participated in advisory boards on behalf of Takeda. The remaining authors declare no competing interests.  

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