Dysbiosis of microbiome and probiotic treatment in a genetic model of autism spectrum disorders
Abstract
Recent studies have determined that the microbiome has direct effects on behavior, and may be dysregulated in neurodevelopmental conditions. Considering that neurodevelopmental conditions, such as autism, have a strong genetic etiology, it is necessary to understand if genes associated with neurodevelopmental disorders, such as Shank3, can influence the gut microbiome, and if probiotics can be a therapeutic tool. In this study, we have identified dysregulation of several genera and species of bacteria in the gut and colon of both male and female Shank3 KO mice. L. reuteri, a species with decreased relative abundance in the Shank3 KO mice, positively correlated with the expression of gamma-Aminobutyric acid (GABA) receptor subunits in the brain. Treatment of Shank3 KO mice with L. reuteri induced an attenuation of unsocial behavior specifically in male Shank3 mice, and a decrease in repetitive behaviors in both male and female Shank3 KO mice. In addition, L. reuteri treatment affected GABA receptor gene expression and protein levels in multiple brain regions. This study identifies bacterial species that are sensitive to an autism-related mutation, and further suggests a therapeutic potential for probiotic treatment.
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Treatment with L. reuteri increased GABA receptor gene expression and protein levels in brain regions of mice and corresponded to improvements in social engagement.
“Treatment with L. reuteri resulted in an increase of both GABA receptor gene expression and protein levels in brain regions of mice, which also corresponded to improvements in social engagement.”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [84]
In a rodent model, L. reuteri was sensitive to an autism-related mutation, decreased in abundance, and positively correlated with GABA receptor expression in the brain.
“In a rodent model, Tabouy et al. [84] used the Shank3 KO mice and demonstrated that specific bacterial species (i.e. L. reuteri) were sensitive to an autism-related mutation, were decreased in abundance, and positively correlated with the expression of gamma-aminobutyric acid (GABA) receptor in the brain.”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [84]
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- Authors
- Tabouy, L., Getselter, D., Ziv, O., Karpuj, M., Tabouy, T., Lukic, I., Maayouf, R., Werbner, N., Ben-Amram, H., Nuriel-Ohayon, M., Koren, O., & Elliott, E.
- Affiliations
- Bar-Ilan University (IL)
- AgroParisTech (FR)
- Corresponding author
- Elliott, Evan
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 73
- Pages
- 310-319
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2803873435
- Cited by
- 214
- References
- 67
- Citations by year
- 2026: 17 · 2025: 33 · 2024: 37 · 2023: 31 · 2022: 28 · 2021: 25 · 2020: 22 · 2019: 16 · 2018: 5
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- autism spectrum disorder, gut dysbiosis, probiotics, Shank3 knockout mice, Lactobacillus reuteri, repetitive behavior, sex differences, neurodevelopmental disorders
- MeSH terms
- Autism Spectrum Disorder, Gastrointestinal Microbiome, Animals, Behavior, Animal, Brain, Disease Models, Animal, Female, Male, Microfilament Proteins, Models, Genetic, Nerve Tissue Proteins, Receptors, GABA, Mice, Knockout, Probiotics, Mice, Limosilactobacillus reuteri, Dysbiosis
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