Sturgeon, J.P., Mutasa, K., Bwakura-Dangarembizi, M., Amadi, B., Ngosa, Deophine and Playford, Raymond J. ORCID: https://orcid.org/0000-0003-1235-8504 (2024) Therapeutic interventions targeting enteropathy in severe acute malnutrition modulate systemic and vascular inflammation and epithelial regeneration. The Lancet, 111. ISSN 0140-6736

PDF (6 month embargo) Therapeutic interventions targeting enteropathy in Severe Acute Malnutrition modulate systemic and vascular inflammation and epithelial regeneration.pdf - Accepted Version Restricted to Repository staff only until 10 June 2025. Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (1MB)

Abstract

Background
Severe acute malnutrition (SAM) is the most life-threatening form of undernutrition, and children hospitalised with complications have unacceptably high mortality. Complicated SAM is a multisystem disease characterised pathophysiologically by muscle wasting, systemic inflammation, metabolic dysfunction, and malnutrition enteropathy including epithelial barrier dysfunction. There is a clear need for novel interventions to address the underlying pathogenic perturbations of complicated SAM.
Methods
In this analysis of tertiary outcomes from a phase II multi-centre trial in Zambia and Zimbabwe, multiplex biomarkers were measured in 122 children (57% male) with SAM randomised following stabilisation (‘baseline’) to one of four interventions for 14 days to treat malnutrition enteropathy: budesonide, N-acetylglucosamine, colostrum, or teduglutide, compared with standard-of-care. Following measurement of 35 biomarkers from day 15 plasma samples using Luminex and ELISA, the dimensionality of biomarker data was reduced using principal component analysis.
Findings
Both budesonide and colostrum reduced systemic inflammation (as measured by CD14, IL1-ra, CRP, and LBP), while children receiving colostrum had higher GLP2 and angiopoietin, and lower circulating lipopolysaccharide, suggesting better restoration of epithelial barrier function. N-acetylglucosamine, a precursor for epithelial glycosaminoglycan synthesis, increased biomarkers of epithelial regeneration (EGF, VEGF), and circulating growth factors (angiopoietin, IGFBP-3, and GCSF).
Interpretation
Interventions aimed at ameliorating malnutrition enteropathy showed plausible effects on biomarkers of inflammation and epithelial regeneration, demonstrating an interdependence of systemic inflammation and enteropathy markers seen in structural analysis. Given the interplay between inflammation and tissue restoration in malnutrition, this mechanism of action supports larger trials to determine the clinical benefits of interventions, either alone or in combination, in children with complicated SAM.

Item Type:	Article
Identifier:	10.1016/j.ebiom.2024.105478
Subjects:	Medicine and health
Depositing User:	Marc Forster
Date Deposited:	16 Dec 2024 11:39
Last Modified:	16 Dec 2024 11:45
URI:	https://repository.uwl.ac.uk/id/eprint/12997

Actions (login required)

View Item