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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-06-01
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| 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. |
| format | Article |
| id | doaj-art-7b7f7d8155684b9c87db63138f56bcaa |
| institution | Kabale University |
| issn | 2813-4338 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiomes |
| 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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