Multi-omics, multi-tissue analysis reveal role of extracellular matrix remodeling and sphingolipid homeostasis in edematous malnutrition (kwashiorkor)
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Edematous malnutrition, aka kwashiorkor, is a phenotype of severe malnutrition whose pathophysiology remains poorly understood. METHODS: In this case-control study, we employed plasma lipidomics, metabolomics, and proteomics, urine metabolomics and gut microbiome profiling to delineate molecular features specific to kwashiorkor in 60 children aged 6-59 months from Niger compared to marasmus (n = 60) and non-malnourished children (NAM) (n = 60) matched by age, sex, and clinical triage score. Features were defined as kwashiorkor-specific if they also correlated with edema severity and normalized following nutritional rehabilitation. RESULTS: We identified a plasma proteomic factor featuring lumican, gelsolin, and tetranectin and a lipidomic factor enriched in sphingolipids. Both differed in kwashiorkor compared to marasmus and NAM, were associated with edema grade, and trended towards normalcy after nutritional treatment, which are consistent with ECM remodeling and sphingolipid dysregulation. In contrast, neither (plasma and urine) metabolomic profiles nor gut microbiome composition showed kwashiorkor-specific signatures, although our urine and gut microbiome analyses may be underpowered. CONCLUSION: These findings advance understanding of kwashiorkor pathophysiology beyond nutrient deficiency and highlight ECM and sphingolipid features associated with its distinct clinical and molecular characteristics compared to marasmus.
Source: Biomarker Research
Authors: Fabienne Nackers, Kirrily de Polnay, Ruben Almey, Simon Daled, Azahir Dan Djibo, Sarah De Saeger, Dieter Deforce, Maarten Dhaenens, Yannick Gansemans, Griet Glorieux, Ousmane Guindo, Benjamin Jenkins, Albert Koulman, Hans-Joerg Lang, Céline Langendorf, Debby Laukens, Christopher Mambula, Isabelle Mukagatare, Damon Parkington, Elh Ibrahim Tassiou, Wim Van Biesen, Tom Van De Wiele, Jill Van Massenhove, Filip Van Nieuwerburgh, Irène Adehossi, André Briend, Gerard Bryan Gonzales
Institutions: Epicentre, Médecins Sans Frontières, Médecins Sans Frontières, Ghent University, Ghent University Hospital, MRC Elsie Widdowson Laboratory, University of Cambridge, Wellcome/MRC Institute of Metabolic Science, Addenbrooke's Hospital, Wellcome Trust, Medical Research Council, Heidelberg University, Alliance for International Medical Action, Heidelberg Institute of Global Health, VIB-UGent Center for Inflammation Research, Médecins Sans Frontières, National Hospital Niamey, University of Copenhagen, Tampere University, Tampere University Hospital, University of Tampere
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,890
OpenAlex ID: W7224238245