Lactobacillus (L.) reuteri and mouse-modelled autism: spotlight on the vagus nerve?

I am a little late getting to the findings reported by Martina Sgritta and colleagues [1] but I eventually arrived at them. As per the title of this post - "Lactobacillus (L.) reuteri and mouse model autism: spotlight on the vagus nerve?" - there were a number of important elements to this research covering mouse-modelled autism, the "gut-microbiota-brain axis", and something called the vagus nerve. Pretty good fodder for this blog by all accounts, given some past discussions (see here) including mention of previous research from some of the Sgritta paper co-authors (see here).

So, continuing a theme from this research group suggesting that, in mice at least, some pregnancy 'risk factors' for autism might have a microbial connection [2], authors set out to examine whether the inclusion of a specific bacterial species called Lactobacillus reuteri or L. reuteri for short might have some important effect on the social behaviour of a mouse model of autism. L. reuteri has been the source of quite a bit of study down the years [3] as a function of it's antimicrobial activity and connection to inflammatory conditions. Outside of the Baylor College group research, this bacterial species has also been talked about with autism in mind [4] in other studies, as per conclusions like: "This study identifies bacterial species that are sensitive to an autism-related mutation." I'll say no more on that study for now aside from offering a viewpoint from elsewhere on the web.

Alongside their observation that "treatment with L. reuteri selectively rescues social deficits in genetic, environmental, and idiopathic ASD [autism spectrum disorder] models" Sgritta et al also put a little scientific flesh on what underlying mechanism(s) might be pertinent to such 'rescuing' of social issues. You might think it was something to do with the contribution of L. reuteri to the gut microbiome of the [mouse] host? Well, yes and no, as authors highlighted how "L. reuteri acts in a vagus nerve-dependent manner" so bringing in the notion that bacteria in the gut *talk to* the brain (or the wider central nervous system) via the vagus nerve. The paper by Bruno Bonaz and colleagues [5] provides as good an explanation as any of how bacteria talk to the brain and what this means for the "gut-microbiota-brain axis." Interestingly too, authors mention how when the vagus nerve was 'disrupted' in said mouse-modelled autism, so the the gut-microbiota-brain link was also disrupted, and onward that L. reuteri didn't seemingly work as well at rescuing those social issues. They also talk about a role for oxytocin receptors in their findings similar to their last research occasion, but I'm going to leave that for now. All I will say is that oxytocin has also been mentioned in other autism research circles (see here).

Obviously, there are caveats to the Sgritta findings; not least that mouse-modelled autism is just mouse-modelled autism and probably not totally representative of real-life human autism (see here). Generalisations of the social behaviour of mice raised and living under laboratory conditions to people (children and adults) traversing the big, wide real world always require a degree of caution.

But I am interested in this area and would like to see more study done on the "gut-microbiota-brain axis" with autism in mind. Given that L. reuteri is freely available to anyone and everyone and seems to have quite a good safety record, I'd perhaps suggest that a clinical trial could be something that a young, upcoming researcher or research group might possibly want to consider exploring...

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[1] Sgritta M. et al. Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder. Neuron. 2018 Dec 3. pii: S0896-6273(18)31009-2.

[2] Buffington SA. et al. Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell. 2016 Jun 16;165(7):1762-1775.

[3] Mu Q. et al. Role of Lactobacillus reuteri in Human Health and Diseases. Front Microbiol. 2018;9:757. 

[4] Tabouy L. et al. Dysbiosis of microbiome and probiotic treatment in a genetic model of autism spectrum disorders. Brain Behav Immun. 2018 Oct;73:310-319.

[5] Bonaz B. et al. The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Front Neurosci. 2018;12:49. 

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