Zinc is a Key Regulator of Gastrointestinal Development, Microbiota Composition and Inflammation with Relevance for Autism Spectrum Disorders
Cellular and Molecular Life Sciences(2021)
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.
MoreTranslated text
Key words
Zn,ASD,Gastrointestinal,Microbiome,Neuroinflammation,Intestinal organoids
AI Read Science
Must-Reading Tree
Example
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined