ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1607045
This article is part of the Research TopicThe Interaction Between Food Ingredients and Gut Microbiome on Health and DiseaseView all 29 articles
Effect of dietary zinc supplementation on the gastrointestinal microbiome and host gene expression in the Shank3B -/-mouse model of autism spectrum disorder
Provisionally accepted
- The University of Auckland, Auckland, New Zealand
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Shank gene variants are implicated in ~1% of people with autism, and mice lacking Shank3 exhibit autism-like behaviours. Zinc deficiency and gastrointestinal problems can be common among people with autism, and zinc is a key element required for SHANK protein function and gut development. In Shank3B -/-mice, a supplementary zinc diet reverses autism-like behaviours. We hypothesise that dietary zinc may alter the gut microbiome, potentially affecting the gut-microbiome-brain axis, which may contribute to changes in autism-like behaviours. To test this, four types of gastrointestinal samples (ileum, caecum, colon, faecal) were collected from Shank3B -/-wild-type and knock-out mice on either control or supplemented-zinc diets, enabling us to examine the influence of -and interactions between -dietary zinc, the gut microbiome, and ASD-linked host genotype. Cage, genotype, and zinc diet each contributed significantly to bacterial community variation (accounting for 12.8%, 3.9%, and 2.3% of the variation, respectively). Fungal diversity was significantly lower in Shank3B -/-compared with wildtype mice on the control zinc diet, with specific fungal biota signatures detected among gut locations. Host metabolic genes, which may be regulated by the gut microbiota, and host genes involved in antimicrobial interactions were more highly expressed in Shank3B -/-mice. Metagenomic analyses revealed differential abundance of bacterial fatty acid biosynthesis and transporters (including zinc transport and neurotransmitter receptors) among our experimental groups. Overall these suggested increased activity of, or a switch towards, metabolic and microbial-host interactions that may benefit both host and microbe, in the presence of zinc. This raises the potential of manipulating both dietary zinc and the gut microbiota itself to ameliorate ASD-related behaviours and associated gastrointestinal issues. These data broaden understanding of the gut microbiome in autism and pave the way toward potential microbial therapeutics for gastrointestinal problems in people with autism.
Keywords: Autism Spectrum Disorder, mouse model, Shank3, gut microbiome, Host gene expression, Bacteria, Fungi, Zinc
Received: 07 Apr 2025; Accepted: 24 Jul 2025.
Copyright: © 2025 Wong, Jung, Lee, Fourie, Handley, Montgomery and Taylor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mike Taylor, The University of Auckland, Auckland, 1142, New Zealand
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.