Autism, the Regulatory Immune System and Microbiome Alterations

Yet another paper was just published this week, confirming yet again that children on the autism spectrum have both dysregulated immune systems and altered bacterial microbiomes.[i]

There were certainly some particularly interesting and novel findings in this research.

The study consisted of 4 groups of children (a total of 103 were involved):  one with autism and GI symptoms (irregular bowel habits), one with just autism and no GI issues, one with typically developing children with GI issues and one group of typically developing children and no GI issues.  Blood from each child was assessed after stimulating the immune system, and also, microbiome analyses were done on the children’s stools.

The children with autism and gut issues produced increased levels of inflammatory cytokines that affect the gut mucosa and these children also produced lower levels of the regulatory cytokine TGFβ1 (Transforming growth factor beta 1).  Remember that the regulatory system modulates our inflammatory response and thus, these children were less able to regulate their levels of inflammation.  (To boot, TGFβ1 plays a role in neurodevelopment, adding yet another connection between the symptoms of autism and a dysregulated immune system.)  Previous research has already shown that other important regulatory cytokines, like IL-10, are low in children on the spectrum.[ii]

One especially interesting finding is that TGFβ1 was dysregulated in both sets of children with autism, which suggests that even those without GI symptoms are affected by excess inflammation.

“’Some children with ASD have this decrease in regulatory cytokines, which leaves them more prone to inflammation,’ said Destanie Rose, a graduate student in the laboratory of Paul Ashwood and first author on the paper. ‘This increased inflammation may manifest as GI symptoms, allergies, asthma or some other form.’”[iii]

There were distinct differences too in the microbiomes of children (both with autism and typically developing) who had GI symptoms – but there were also differences between the children with autism and their neuro-typical peers.  One finding in the paper that I had never read before:  the children with autism and GI symptoms “…showed an over-representation of the gene encoding zonulin, a molecule regulating gut permeability…”

The authors conclude that the decrease in the regulatory part of the immune system is highly significant, putting the children at tremendous risk of inflammatory issues.  Of course, if these immune system abnormalities are actually responsible for autism, or which comes first, the abnormal immune system or the microbiome alterations, are as yet unknown.

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[i] Rose, DR, et. al. Differential immune responses and microbiota profiles in children with autism spectrum disorders and co-morbid gastrointestinal symptoms.  Brain, Behavior and Immunity. 2018 Mar 20. pii: S0889-1591(18)30078-3. doi: 10.1016/j.bbi.2018.03.025.

[ii] Bryn, V, Aass,  Hc, Skjeldal, OH, Isaksen, J, Saugstad, OD, Ormstad, H. Cytokine profile in autism spectrum disorders in children. Journal of Molecular Neurosciences. 2017. 61(1):1-7.

[iii] http://www.ucdmc.ucdavis.edu/publish/news/newsroom/12807