An unconventional approach has successfully reversed deficits in social behaviors associated with autism spectrum disorders (ASD) in genetic, environmental and idiopathic mouse models of the condition. Researchers report in the journal Neuron that administration of the bacterium Lactobacillus reuteri could lead to specific changes in the brain that social deficits through a reverse mechanism involve the vagus nerve That and the oxytocin-dopamine reward system. These findings hold hope for the development of novel therapies for neurological disorders by modulating specific microbes in the gut.
"In 2016, we discovered in mice that the offspring of mothers fed a high-fat diet had social deficits and changes in their gut microbiome characterized by a reduction in the abundance of the bacterium L. reuteri More importantly, restoring L. reuteri levels in the offspring reversed their social deficits , "said corresponding author Dr. Mauro Costa-Mattioli." However, this model of ASD represents Only one of the numerous underlying mechanisms of the condition, therefore, we decided to investigate whether our findings would apply to other models with different origins. "
Causes of ASD
The causes of ASD could be of genetic, environmental or idiopathic origin, Costa-Mattioli explains, and there are mouse models mimicking each of these conditions. So, the researchers investigated whether L. reuteri could also rescue social behavior in other mouse models that represent different causes of ASD. Surprisingly, they discovered that, indeed, L. reuteri can trigger the recovery of social behaviors in all the models they tested, suggesting that this microbial-based approach could improve social behavior in a wider subset of ASD.
The researchers then applied multiple techniques to explore the mechanism that mediates L. reuteri's rescue of social behavior in a mouse model of ASD. "We discovered that L. reuteri promotes social behavior via the vagus nerve, which bidirectionally connects the gut and the brain, "said first author Dr. Martina Sgritta, a postdoctoral associate in the Costa-Mattioli lab.
It is known that when the vagus nerve is active, it releases oxytocin, to hormone that promotes social interaction. Oxytocin is released into the reward areas of the brain where it binds to molecules called oxytocin receptors, triggering 'social reward.' Sgritta and colleagues tested whether the vagus connection between the gut and the brain interfering with oxytocin binding to its receptors would affect L. reuteri could not restore social behavior's ability to restore social behaviors in mouse models of ASD mice.
"We have begun to decipher the mechanism by which a gut microbe modulates brain function and behaviors." This could be a key in the development of new more effective therapies, "Costa-Mattioli said. "Indeed, we think that our findings have strengthened the rather unconventional idea that it might be possible to modulate specific behavior through the gut microbiome using select bacterial strains."
Collectively, the findings described here could radically change the way we think about ASD and its treatment and could have a profound influence in the lives of people with this and related disorders.