BRIEF RESEARCH REPORT article

Front. Microbiomes

Sec. Omics and Bioinformatics for Microbiomes

Volume 4 - 2025 | doi: 10.3389/frmbi.2025.1628819

Gut microbiota diversity is altered in a sex-dependent manner in Shank3B heterozygote mice

Provisionally accepted
Finley TurnerFinley TurnerMykle WilliamsMykle WilliamsSophie GregorettiSophie GregorettiDelano BielamowiczDelano BielamowiczKylie RoachKylie RoachLil GehnerLil GehnerAnjali KunnathaAnjali KunnathaShekinah PhillipsShekinah PhillipsRosie HagelRosie HagelRebecca HarshmanRebecca HarshmanErika VargoErika VargoStacey Beanna Bernice DuttonStacey Beanna Bernice DuttonJennifer KovacsJennifer KovacsJennifer LarimoreJennifer Larimore*
  • Agnes Scott College, Decatur, United States

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The gut-brain axis is a dynamic interface that has been implicated in the pathogenesis and severity of various neurodevelopmental disorders such as schizophrenia (SZ) and autism spectrum disorders (ASD). Also implicated in ASD and SZ, SHANK3B is a critical gene for postsynaptic protein scaffolding at excitatory synapses. Shank3B knockout mice not only exhibit ASD-like behaviors but demonstrate altered gastrointestinal epithelium morphology and fecal microbiota composition. Utilizing Shank3B heterozygote mice to better reflect the clinical presentation of ASD, we sequenced the gut microbiome from the small intestine of 12-week-old wild type Shank3B +/+ or Shank3B +/-mice in a sex-dependent manner, analyzing bacterial phyla, classes, orders, families, genera, and species. Firmicutes emerged as the dominant phylum in Shank3B +/-mice and Bacilli as the dominant class, with Lactobacillales as the dominant order. The dominant family is Lactobacillaceae. The Shank3B +/- males but not the Shank3B +/-females show an increase in Staphylococcaceae and Erysipelotricaceae. Our results indicate increased biodiversity in Shank3B +/-males and reduced biodiversity in Shank3B +/-females compared to wild-type controls. Altogether, this data reveals sex-specific microbial signatures that may contribute to the pathogenesis of ASD thus providing potential therapeutics that target gut microbiota in neurodevelopmental disorders.

Keywords: microbiome, Schizophrenia, Autis Spectrum Disorder, Gut - brain axis, Neurodevelomental Disorders

Received: 14 May 2025; Accepted: 06 Jun 2025.

Copyright: © 2025 Turner, Williams, Gregoretti, Bielamowicz, Roach, Gehner, Kunnatha, Phillips, Hagel, Harshman, Vargo, Dutton, Kovacs and Larimore. 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: Jennifer Larimore, Agnes Scott College, Decatur, United States

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.

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