Zinc is a key regulator of gastrointestinal development, microbiota composition and inflammation with relevance for autism spectrum disorders

Ann Katrin Sauer, Sigita Malijauskaite, Paula Meleady, Tobias M. Boeckers, Kieran McGourty, Andreas M. Grabrucker

Research output: Contribution to journalArticlepeer-review

Abstract

Gastrointestinal (GI) problems and microbiota alterations have been frequently reported in autism spectrum disorders (ASD). In addition, abnormal perinatal trace metal levels have been found in ASD. Accordingly, mice exposed to prenatal zinc deficiency display features of ASD-like behavior. Here, we model GI development using 3D intestinal organoids grown under zinc-restricted conditions. We found significant morphological alterations. Using proteomic approaches, we identified biological processes affected by zinc deficiency that regulate barrier permeability and pro-inflammatory pathways. We confirmed our results in vivo through proteomics studies and investigating GI development in zinc-deficient mice. These show altered GI physiology and pro-inflammatory signaling, resulting in chronic systemic and neuroinflammation, and gut microbiota composition similar to that reported in human ASD cases. Thus, low zinc status during development is sufficient to compromise intestinal barrier integrity and activate pro-inflammatory signaling, resulting in changes in microbiota composition that may aggravate inflammation, altogether mimicking the co-morbidities frequently observed in ASD.

Original languageEnglish
Article number46
Pages (from-to)46
JournalCellular and Molecular Life Sciences
Volume79
Issue number1
DOIs
Publication statusPublished - Jan 2022

Keywords

  • ASD
  • Gastrointestinal
  • Intestinal organoids
  • Microbiome
  • Neuroinflammation
  • Zn

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