Transcriptome, glycome, and mucinome analysis reveal zinc is essential for the composition of mucus in the human goblet cell model HT-29-MTX.

Authors

Christoph Schüßler, Nara Chung, Renaud Léonard, Heike Sprenger, Tari Rödel, Keira E Mahoney, Susanne Thomsen, Esther Ocket, Claudia Matthaeus, Jordan Denis, Franziska Ebert, Marvin Wolf, Willy Morelle, François Foulquier, Albert Braeuning, Catherine Robbe Masselot, Stacy A Malaker, Maria Maares

Published in

Scientific reports. Volume 16. Issue 1. Aug 11, 2026. Epub Aug 11, 2026.

Abstract

Zinc (Zn) deficiency affects approximately 1 billion people worldwide with severe consequences for their health, including increased intestinal infections, inflammation, and diarrhea. Accordingly, the intestinal defense barrier is compromised, leading to epithelial destruction and alteration of mucus. However, the processes and the extent to which Zn deficiency affects mucin synthesis in intestinal goblet cells (GCs) remain poorly understood. To this end, we investigated the impact of Zn deficiency on mucin expression and glycosylation in the human GC model HT-29-MTX. Zn deprivation altered the GC transcriptome, affecting genes involved in Zn transport, mucin synthesis and glycosylation. Accordingly, mucus composition was changed in Zn-deficient GCs, significantly increasing MUC2 and MUC17 on the mRNA and protein level. Several Zn transporters, mostly those associated with the early secretory pathway (ESP), were dysregulated, indicating an adaptive response of cellular Zn homeostasis. Additionally, free Zn was markedly reduced in the ESP, a critical location for glycosylation. Zn deficit substantially changed mucin glycosylation, characterized by an increase in sialylation and a strong decrease in complex N-glycans. All these changes involved widespread dysregulation of glycosyltransferase expression, including an increase in COSMC, a Zn-binding chaperone essential for the core 1 O-glycan formation. Collectively, our in vitro findings demonstrate that Zn is a critical regulator of mucin production and glycosylation in GCs. Zn deficiency might weaken the protective and functional qualities of intestinal mucus, increasing the risk of infections and potentially disrupting host-microbiome interactions.

PMID:
42575931
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.

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