Autism spectrum disorder (ASD) mouse model — improved by gut bacteria ???

Autism spectrum disorder (ASD) is a great example of a gene-environment interactions topic — i.e. fitting in perfectly to these GEITP pages. Clearly there are hundreds, if not thousands, of small-effect genes that contribute to genetic susceptibility (to be afflicted with ASD), but it is likely there are epigenetic effects and environmental factors that play a role. Any participation of endogenous conditions (normal physiology or abnormal pathophysiology), or influence by one’s microbiome, is something that must also be considered. ASD in Western societies, just like obesity and type-2 diabetes, continues to be on the rise. Why? What the heck is going on?

Defined as a heterogeneous neurodevelopmental disorder, ASD is characterized by social deficits, repetitive behaviors, and language difficulties. In addition to these core symptoms — ASD patients often suffer from gastrointestinal (GI) issues; in fact, children with ASD are 3.5 times more likely to suffer from GI disorders than children without developmental disorders. Moreover, GI problems have been associated with changes in the microbial communities inhabiting the gut of ASD individuals. Studies in animal models have shown that gut microbes can modulate central nervous system (CNS)-driven behaviors in very powerful ways.

Authors [of the attached article] recently found that the bacterial species — Lactobacillus reuteri — reverses social deficits in maternal high-fat-diet mouse 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. [In the attached article], authors show that L. reuteri treatment selectively rescues social deficits in genetic, environmental, and idiopathic ASD models. Interestingly, effects of L. reuteri on social behavior are not mediated by restoring the composition of the host’s gut microbiome (which was found to be altered in all of these ASD models). Instead, L. reuteri acts via the vagus nerve, and rescues social interaction-induced synaptic plasticity in the ventral tegmental area of the brains of ASD mice, but not in oxytocin receptor-deficient [Oxtr(-/-)] mice. These studies therefore suggest that L. reuteri treatment emerges as a promising non-invasive microbial-based avenue to combat ASD-related social dysfunction..!! 🙂


Neuron 2o19; 101: 246-259

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