One of the most exciting new studies that I've recently has been that from a group lead by Paul Patterson from Caltech (Cell 155, 1451–1463). Their study has shown
that a simple probiotic therapy could improve the symptoms of autistic spectrum
disorder (ASD). This study breaks new ground in linking diet and the disorder.
Previously, it had been noted that there was a correlation between ASD patients
and gastrointestinal disorders such as Inflammatory Bowel Disease (IBD), and
there had been some reports of alleviated symptoms through adoption of
exclusionary diets such as gluten- or casein-free regimens. Now a new study published
in Cell shows could provide some concrete basis through which these diets may have their differing effects on different people. Their results suggests that the state of the gut health in ASD
patients is more to do with an imbalance of gut microbiota, rather than
specific dietary intolerances
The group were able to make this discovery after studying mouse models for
ASD. One particular type of mouse frequently used is the maternal immune
activation (MIA) model, which involves injecting the expectant mothers with a
viral mimicking chemical. The immune response from the mothers is thought to
affect the development of the embryos and results in offspring that are less
social, have increased and anxiety and display more repetitive activity.
Crucially, they also seem to display the associated alimentary disturbances such
as increased gut wall permeability (“leaky gut”). This means that the intestinal wall is not able to filter all metabolites and biomolecules at the same level as a healthy gut. It can be detected by the increased translocation of certain sugars and also an increase of specific immune
factors, such as CLDN 8, 5 and IL-6 in response.
Based on emerging and
increasingly compelling evidence that gut microbiota have impacts on
personality and social development, affecting a range of emotional issues such
as appetite and mate choice, the team investigated further whether there were any differences
in the gut commensals between the healthy and ASD mice. After sequencing both
sets of organisms, they found the largest difference in the Clostridia and Bacteroides genera.
Since B. fragilis is a common human commensal, Patterson tested the
theory whether dietary replacement of this species would have any impact on the
MIA mice. In fact, not only did B.
fragilis treatment improve ASD behavioural features, resulting in increased
social interactions and reduced anxiety and repetitive behaviour, but also ameliorated
all the associated gut disturbances and immune responses.
It could be that in certain individuals excluding gluten or casein from their diet happened to tip the equilibrium of gut microbiota back towards a healthy level. However since everyone's commensal bacteria come from a complex range of sources from their environment, this change in diet would affect different individuals to different extents, which may explain the varying efficacy of diet change in ASD.
Moreover, since ASD diagnoses are constantly on the increase, as well as other diseases with possible auto-immune causes, for example asthma and IBS, it could be that ASD is another result from our increasingly sterile environment. With the recent advances of controversial therapies, such as "helminthic therapy" to treat Crohn's disease, gaining ground, evidence increasingly suggests that keeping entirely disease-free is not a healthy or natural state for humanity, and that attempting to do so has repercussions. The main thrust of the helminthic therapy relies on the fact that helminths release immune-repressing molecules to avoid detection and destruction by the host's immune response. Since modern-day hygiene is relatively recent, this means that the vast majority of humans during evolutionary time were carrying helminths, and thus, the immune response adapted to an equilibrium with their presence. Their sudden removal has meant that the immune response is not kept in check in the same way, and could be going into overdrive, attacking the host's own cells. Moreover, since now we are several generations in to our new, clean world, this could result in mother's having less experienced immune systems, meaning that they are more susceptible to infections during pregnancy, which could result in a similar outcome as the MIA infection model mice. The recent findings that changes in the brain associated with autism could be detected before birth, while the baby was still in the womb, only highlight the importance of the mother's health during pregnancy.
Although further studies are
required to create a solid basis of probiotic therapy, the authors note that these findings give hope
to a tantalisingly safe, easy and cost-effective treatment for ASD, and possibly
other neurological disorders with similar behavioural traits, such as schizophrenia, which has similar anxiety and social impairment problems. It also gives further proof of the importance of the delicate balance between ourselves and our commensals.
