New research has demonstrated how gut bacteria may reverse autism related behaviour in mice. It is believed a single type of bacteria may reverse these symptoms in humans.
Autism is a condition which affects the social functioning, communication and interaction of an afflicted individual. Usually explained as caused by a combination of genetic and environmental effects, a more complete and convincing explanation may be still needed. Recently the focus has turned to the immune system in particular the microbiome. The gut microbiome is an individual ecosystem of microorganisms composed of bacteria and pathogens which predict and maintain the health. In man a specialised community of microbes exist in the gut’s warm environment all having a specific function. The makeup of this “ecosystem” may vary by 80-90% depending on the diet of an individual and previous research on medical records suggests overweight mothers were much more likely to have offspring with Autism.
As ASD often involves a simultaneous imbalance of gut microbiota, Buffington and colleagues set out to determine whether a high fat diet alters the gut microbiota in mice offspring. Aiming to evaluate the effect of maternal diet on offspring’s social and synaptic functioning, mice were fed regular diets or diets high in fat for 8 weeks, usually the time taken to develop obesity. Firstly, mice on a high fat diet had smaller litters. When compared, the offspring of mice on a high fat diet exhibited fewer reciprocal social interactions than mice with mothers on a regular diet. Although both groups of mice possessed Bacteroidetes and Firmicutes, — a typical bacteria found in mic —, a marked difference in the structures of bacterial communities was found. A reduced diversity of microbiota in offspring of mice on a high fat diet was discovered by analysing the bacterial makeup of faeces using (rNA) gene sequencing. This alteration was also observed in the maternal mice microbiome composition.
An interesting component of the experiment housed both groups of offspring (high and regular maternal diets) together to establish whether the microbiota of the mice may be transferred. As mice are coprophagic (transfer microbiota) the team speculated whether this may reverse the effects of a maternal high fat diet and the consequent social deficits. Remarkably, the co-housed mice displayed normal social interactions while earlier deficits were reversed. A striking reversal of the microbiota imbalance to reflect the offspring of mice on a regular diet, likewise emerged.
Among the specific bacteria most reduced by the high fat diet was L. reuteri. This is known to promote oxytocin levels, is important in social behaviours and absent in Autism. Later, treatment with L. reuteri improved sociability significantly in the high fat diet offspring. This treatment had little effect on the normal diet offspring suggesting these mice had ample amounts of the bacteria.
The high fat diet offspring possessed significantly fewer oxytocin secreting neurons in the hypothalamus in comparison to the normal diet offspring. The team found L.reuteri treatment restores the number of oxytocin neurons to normal levels in these mice. In addition, synaptic strengthening (LTP) was induced in an area of the brain called the ventral tegmental area (VTA) only in offspring of the regular diet mice. This region is involved in reward, social behaviours and activated by oxytocin. Treatment with L. reuteri stimulates (LTP) in this brain region in a high fat diet offspring mouse after social interaction.
“The response to social interaction was moderated by synaptic potentiation in a key reward area of the brain which was seen in the normal control mice,” says lead author Costa-Mattiol. When the bacteria were put back in the maternal high fat diet offspring, synaptic function was also restored in the reward circuitry.” The team now envisage a future treatment for Autism. “Other research groups are aiming to use drugs or electrical brain stimulation as a way to reverse some of the behavioural symptoms associated with neurodevelopmental disorders, however here is a new approach,” says Mauro Costa-Mattioli. “Whether it may be effective in humans, is unknown however it is an exciting way of affecting the brain from the gut.”
How may breakthroughs in sciences outside neuroscience aid the understanding of neurodevelopmental conditions?