Organoids as a model to study intestinal and liver dysfunction in severe malnutrition

José M. Horcas-Nieto, Christian J. Versloot, Miriam Langelaar-Makkinje, Albert Gerding, Tjasso Blokzijl, Mirjam H. Koster, Mirjam Baanstra, Ingrid A. Martini, Robert P. Coppes, Céline Bourdon, Sven C.D. van Ijzendoorn, Peter Kim, Robert H.J. Bandsma*, Barbara M. Bakker*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
110 Downloads (Pure)

Abstract

Hospitalized children with severe malnutrition face high mortality rates and often suffer from hepatic and intestinal dysfunction, with negative impacts on their survival. New treatments cannot be developed without understanding the underlying pathophysiology. We have established and characterized translational organoid models of severe malnutrition of the liver and the intestine. In these models, amino acid starvation recapitulates the expected organ-specific functional changes (e.g., hepatic steatosis, barrier dysfunction) accompanied by reduced mitochondrial and peroxisomal proteins, and altered intestinal tight junction proteins. Re-supplementation of amino acids or pharmacological interventions with rapamycin or fenofibrate lead to partial recovery. Restoration of protein levels aligned with signs of improved peroxisomal function in both organoids, and increased mitochondrial proteins and tight junction protein claudin-3 in intestinal organoids. We present two organoid models as novel tools to gain mechanistic insights and to act as a testing platform for potential treatments for intestinal and hepatic dysfunction in severe malnutrition.

Original languageEnglish
Article number166635
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1869
Issue number3
DOIs
Publication statusPublished - Mar-2023

Keywords

  • Amino acids
  • Malnutrition
  • Mitochondria
  • Organoids
  • Peroxisomes

Fingerprint

Dive into the research topics of 'Organoids as a model to study intestinal and liver dysfunction in severe malnutrition'. Together they form a unique fingerprint.

Cite this