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Neuron. 2018 Dec 3. pii: S0896-6273(18)31009-2. doi: 10.1016/j.neuron.2018.11.018. [Epub ahead of print]

Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder.

Author information

1
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Memory and Brain Research Center, Baylor College of Medicine, Houston, TX 77030, USA.
2
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Memory and Brain Research Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
3
Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA.
4
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
5
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Memory and Brain Research Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: costamat@bcm.edu.

Abstract

Currently, there are no medications that effectively treat the core symptoms of Autism Spectrum Disorder (ASD). We recently found that the bacterial species Lactobacillus (L.) reuteri reverses social deficits in maternal high-fat-diet offspring. However, whether the effect of L. reuteri on social behavior is generalizable to other ASD models and its mechanism(s) of action remains unknown. Here, we found that treatment with L. reuteri selectively rescues social deficits in genetic, environmental, and idiopathic ASD models. Interestingly, the effects of L. reuteri on social behavior are not mediated by restoring the composition of the host's gut microbiome, which is altered in all of these ASD models. Instead, L. reuteri acts in a vagus nerve-dependent manner and rescues social interaction-induced synaptic plasticity in the ventral tegmental area of ASD mice, but not in oxytocin receptor-deficient mice. Collectively, treatment with L. reuteri emerges as promising non-invasive microbial-based avenue to combat ASD-related social dysfunction.

KEYWORDS:

autism; dopamine; gut-microbiota-brain axis; microbiome; oxytocin; probiotic; social behavior; vagus nerve

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