• Paris, 12 January 2016  Is autism hiding in a fold of the brain ? 
• 2014 - Atypical sulcal anatomy in young children with autism spectrum disorder 
• 2011 - Early Brain Overgrowth in Autism Associated with an Increase in Cortical Surface Area Before Age 2 
• 2008 - 3D Cerebral Cortical Morphometry in Autism: Increased Folding in Children and Adolescents in Frontal, Parietal, and Temporal Lobes 

Most of this research claims --  an array of genetic changes and environmental conditions   -- are responsible for this unusual folding.

Other research is overlapping here and the emphasis is again  ---  on the gut microbiome, a favorite topic of mine.

Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome 

What they have done is look at bacteria, the type and the amounts, and then correlated those with the structure of the brain.  This was an IBS (Irritable Bowel Syndrome) study, which has connections to autism   - “an increased ratio between the phyla Firmicutes and Bacteroidetes (F-B ratio) which has been reported by several investigators [7–10]....Higher alpha diversity has previously been reported in an IBS subgroup [10], in patients with celiac disease [51], and with autism spectrum disorder [52], all syndromes which are often accompanied by IBS-like symptoms.

It is fascinating as the connections from bacteria types and amounts, to brain volume or folds has yet to be done for autism but a study would be very important.

Moderate-sized correlations with brain structure were observed for certain Firmicutes- and Bacteroides-associated taxa. For example, the Firmicutes-associated Clostridia (higher in IBS1) and the Bacteroidetes-associated Bacteroidia (lower in IBS1) showed correlations with the volume of several subcortical brain regions involved in sensory integration and modulation and the motor cortex. For the majority of these regions, increased volumes were observed with decreases in Bacteroidia taxa and increases in the Clostridia taxa...For the sensory brain regions, it is conceivable that neuroactive or proinflammatory metabolites generated by altered gut microbiota reach the brain, inducing neuroplastic changes. As most patients with IBS symptoms have a longstanding history of symptoms, often dating back to childhood, it is likely that such altered gut microbiota to brain signaling could have shaped the brain from early on in life.

Consider this too, from that same study -- In support of this possibility, we found that the surface area of the posterior insula was associated with the predicted abundance of 20 bacterial genes increased in the IBS1 group.

That’s right.  BACTERIAL genes.

The identified genes included two that influence synthesis/degradation of GHB and glutamate. GHB is a neurotransmitter found naturally at high levels in the intestine that inhibits intestinal peristalsis via GABAB receptors and has sedative effects in the CNS [70, 71]. Glutamate is an excitatory neurotransmitter in the enteric nervous system and in the brain where it also plays an important role in synaptic plasticity….

Interestingly, this study may again show that we need to examine autism in this manner - bacteria vs the brain, especially the issue of abnormal folding:

Altered Intrinsic Functional Connectivity of Anterior and Posterior Insula Regions in High-Functioning Participants With Autism Spectrum Disorder 

Folding of the brain has been shown to be connected to intelligence  .  Could we find out more by looking at these connections  of the “convoluted” folds and the gut bacteria?  We could and hopefully it will be done ----

The low functioning autism group had a prominent shape abnormality centered on the pars opercularis of the inferior frontal gyrus that was associated with a sulcal depth difference in the anterior insula and frontal operculum. The high-functioning autism group had bilateral shape abnormalities similar to the low-functioning group, but smaller in size and centered more posteriorly, in and near the parietal operculum and ventral postcentral gyrus. Individuals with Asperger’s syndrome had bilateral abnormalities in the intraparietal sulcus that correlated with age, intelligence quotient, and Autism Diagnostic Interview-Revised social and repetitive behavior scores……

Early life perturbations of the developing gut microbiota can impact neurodevelopment and potentially lead to adverse mental health outcomes later in life  ….What is clear is that this has profound
implications for our understanding of how environmental
exposures at specific stages of the lifespan may impact
neural plasticity to modify neurobehavioral development,
and what implications this may have for the risk of neurodevelopmental
and neuropsychiatric disorders.

What this could mean is that certain bacteria may actually change the architecture of the brain and functioning, explaining the spectrum of autism from the high functioning patients, to those moderately impacted, to those who are the most severely affected. Environmental exposures may have indeed caused the microbiome to become dysfunctional.

The Michael J. Fox Foundation has made progress in this line of research.  Hopefully autism will follow--

Study shows proteins produced by gut bacteria may cause misfolding of brain proteins and cerebral inflammation  

….clumped proteins produced by bacteria in the gut cause brain proteins to misfold via a mechanism called cross-seeding, leading to the deposition of aggregated brain proteins. He also proposed that amyloid proteins produced by the microbiota cause priming of immune cells in the gut, resulting in enhanced inflammation in the brain.  The research, which was supported by The Michael J. Fox Foundation…..

Teresa Conrick is Science Editor for Age of Autism.