Multi-omics, multi-tissue analysis reveal role of extracellular matrix remodeling and sphingolipid homeostasis in edematous malnutrition (kwashiorkor)
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.
Authors
- Maarten Dhaenens (ORCID: https://orcid.org/0000-0002-9801-3509)
- Albert Koulman (ORCID: https://orcid.org/0000-0001-9998-051X)
- Tom Van de Wiele (ORCID: https://orcid.org/0000-0001-6854-5689)
- Céline Langendorf (ORCID: https://orcid.org/0000-0002-0811-7540)
- Isabelle Mukagatare (ORCID: https://orcid.org/0009-0002-0474-4608)
- Christopher Mambula (ORCID: https://orcid.org/0009-0001-2960-4786)
- Simon Daled (ORCID: https://orcid.org/0000-0001-8129-2217)
- Irène Adehossi
- Kirrily de Polnay
- Dieter L. D. Deforce (ORCID: https://orcid.org/0000-0002-0635-661X)
- Wim Van Biesen (ORCID: https://orcid.org/0000-0002-4782-5224)
- Damon A. Parkington (ORCID: https://orcid.org/0000-0001-5043-5377)
- Sarah De Saeger (ORCID: https://orcid.org/0000-0002-2160-7253)
- Debby Laukens (ORCID: https://orcid.org/0000-0002-1984-5850)
- Yannick Gansemans (ORCID: https://orcid.org/0000-0001-5018-044X)
- Fabienne Nackers (ORCID: https://orcid.org/0000-0001-9870-1910)
- Ruben Almey (ORCID: https://orcid.org/0000-0001-6911-5904)
- Filip Van Nieuwerburgh (ORCID: https://orcid.org/0000-0001-8815-5485)
- Griet Glorieux (ORCID: https://orcid.org/0000-0002-7641-4707)
- Benjamin H. Jenkins (ORCID: https://orcid.org/0000-0002-3803-6418)
- Gerard Bryan Gonzales (ORCID: https://orcid.org/0000-0001-6614-3520)
- Ousmane Guindo
- Jill Van Massenhove
- Elh Ibrahim Tassiou
- Azahir Dan Djibo
- Hans-Joerg Lang
- André Briend
Institutions
- University of Copenhagen (DK)
- Médecins Sans Frontières (UG)
- Tampere University (FI)
- MRC Elsie Widdowson Laboratory (GB)
- Heidelberg University (DE)
- Ghent University Hospital (BE)
- Ghent University (BE)
- Alliance for International Medical Action (SN)
- Wellcome/MRC Institute of Metabolic Science (GB)
- Tampere University Hospital (FI)
- Médecins Sans Frontières (BE)
- VIB-UGent Center for Inflammation Research (BE)
- Addenbrooke's Hospital (GB)
- National Hospital Niamey (NE)
- Médecins Sans Frontières (FR)
- Epicentre (FR)
- University of Tampere (FI)
- Heidelberg Institute of Global Health (DE)
- Wellcome Trust (GB)
Publication Details
- Journal
- Biomarker Research
- Published
- 2026-10-28
- DOI
- https://doi.org/10.1186/s40364-026-01016-9
- Primary Topic
- Child Nutrition and Water Access
- Type
- article
- Field-Weighted Citation Impact
- 0.00