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

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 a...

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Main Authors: Finley Turner, Mykle Williams, Sophie Gregoretti, Delano Bielamowicz, Kylie Roach, Lil Gehner, Anjali Kunnatha, Shekinah Phillips, Rosie Hagel, Rebecca Harshman, Erika Vargo, Stacey B. B. Dutton, Jennifer Kovacs, Jennifer Larimore
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Microbiomes
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Online Access:https://www.frontiersin.org/articles/10.3389/frmbi.2025.1628819/full
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author Finley Turner
Mykle Williams
Sophie Gregoretti
Delano Bielamowicz
Kylie Roach
Lil Gehner
Anjali Kunnatha
Shekinah Phillips
Rosie Hagel
Rebecca Harshman
Erika Vargo
Stacey B. B. Dutton
Jennifer Kovacs
Jennifer Larimore
author_facet Finley Turner
Mykle Williams
Sophie Gregoretti
Delano Bielamowicz
Kylie Roach
Lil Gehner
Anjali Kunnatha
Shekinah Phillips
Rosie Hagel
Rebecca Harshman
Erika Vargo
Stacey B. B. Dutton
Jennifer Kovacs
Jennifer Larimore
author_sort Finley Turner
collection DOAJ
description 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.
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spelling doaj-art-7b7f7d8155684b9c87db63138f56bcaa2025-08-20T03:24:52ZengFrontiers Media S.A.Frontiers in Microbiomes2813-43382025-06-01410.3389/frmbi.2025.16288191628819Gut microbiota diversity is altered in a sex-dependent manner in Shank3B heterozygote miceFinley TurnerMykle WilliamsSophie GregorettiDelano BielamowiczKylie RoachLil GehnerAnjali KunnathaShekinah PhillipsRosie HagelRebecca HarshmanErika VargoStacey B. B. DuttonJennifer KovacsJennifer LarimoreThe 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.https://www.frontiersin.org/articles/10.3389/frmbi.2025.1628819/fullmicrobiomeschizophreniaautism spectrum disordergut-brain axisneurodevelopmental disorders
spellingShingle Finley Turner
Mykle Williams
Sophie Gregoretti
Delano Bielamowicz
Kylie Roach
Lil Gehner
Anjali Kunnatha
Shekinah Phillips
Rosie Hagel
Rebecca Harshman
Erika Vargo
Stacey B. B. Dutton
Jennifer Kovacs
Jennifer Larimore
Gut microbiota diversity is altered in a sex-dependent manner in Shank3B heterozygote mice
Frontiers in Microbiomes
microbiome
schizophrenia
autism spectrum disorder
gut-brain axis
neurodevelopmental disorders
title Gut microbiota diversity is altered in a sex-dependent manner in Shank3B heterozygote mice
title_full Gut microbiota diversity is altered in a sex-dependent manner in Shank3B heterozygote mice
title_fullStr Gut microbiota diversity is altered in a sex-dependent manner in Shank3B heterozygote mice
title_full_unstemmed Gut microbiota diversity is altered in a sex-dependent manner in Shank3B heterozygote mice
title_short Gut microbiota diversity is altered in a sex-dependent manner in Shank3B heterozygote mice
title_sort gut microbiota diversity is altered in a sex dependent manner in shank3b heterozygote mice
topic microbiome
schizophrenia
autism spectrum disorder
gut-brain axis
neurodevelopmental disorders
url https://www.frontiersin.org/articles/10.3389/frmbi.2025.1628819/full
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