The Latest News on the Link Between Autism, Inflammation, Maternal Immune Activation, and the Microbiome

There have been two papers recently on the growing understanding of the relationship between autism and inflammation.  Both, ultimately, point to maternal immune activation (inflammation present in the mother leading to inflammation in her baby) as being the key factor. I’ve covered this topic multiple times on this blog:  the fact that infections like flu, and maternal fevers, are associated with an increased risk of autism should not come as a surprise to my regular readers.  (See here and here.)

The first paper is out of Columbia University, and on the list of authors are some names familiar to those of us long-time autism parents, like Mady Hornig.[i]  The scientists analyzed 60 different immune markers:  “Blood samples were collected during pregnancy (maternal mid-gestational blood sample) and at birth (cord blood) from 957 children, roughly half of whom were later diagnosed with ASD.”[ii]   Yes, I also read that sentence several time:  HALF of the children later developed autism?!  I have no idea what to make of it either.  They found that there is a link to  ASD risk in groupings of inflammation-related molecules, with different groupings seen in boys versus girls.  Two interleuins (IL1RA and IL4) were particularly predictive, and four molecules thought to be involved in fetal brain development were also linked to ASD risk in both sexes: TNFα, Serpin E1, VCAM1, and IL1β.

By the way, when collected at birth, these biomarkers collected at birth were only slightly less predictive than when collected during pregnancy.

So, why is Judy writing about this, this week?  What does all this have to do with the biome?  The second paper, on the same topic, explains the connection.  This study – actually a compilation of 4 studies – was done on mice, and is out of Harvard and MIT.[iii] It pinpoints the missing link in our knowledge.  While the link between autism and MIA has been recognized, the exact mechanism was not known, nor why children with autism have dysrgulated immune systems.  The reason:  “Infections during pregnancy can lead to high levels of the inflammatory signaling molecule interleukin-17a (IL-17a), which can not only affect brain development in the fetus, but also alter the maternal microbiome in a way that primes the newborn’s immune system for future inflammatory attacks.”  Thus, we now see the reason so many with autism also have intestinal inflammation.

In the course of research, the scientists looked at the stool of MIA mice as compared to that of the controls.  Differences were found so as their next step, they transplanted either MIA or control stool into germ-free mice who were then impregnated:  “Unlike with the controls, pups born to mice that received stool from mice with MIA exhibited intestinal inflammation. These results indicate that the altered microbiome of mice with MIA leads to the postnatal immune priming of offspring during rearing.”

Says one of the lead authors, “Thus, increase in IL-17a in moms during pregnancy leads to susceptibility to produce more IL-17a in offspring upon an immune challenge…”

There are so very many unanswered questions: why are the mothers’ microbiomes altered in the first place?  Many mothers have an infection of one sort or another during pregnancy, yet not all babies born to them develop autism.  What differentiates one case from another?  Since humans first stood upright, mothers have developed illnesses during pregnancy.  Why is MIA now more and more of a factor?  What is it about the current maternal immune system that wasn’t present in the past, when autism was rare – if it even existed at all?  You have to suspect that alterations to the biome – from the many factors I have often discussed on this blog (changes in diet, biome depletion, etc.) plays a huge factor in all this but the jury is still out until science gives us answers.
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[i] Che, X., Hornig, M., Bresnahan, M. et al. Maternal mid-gestational and child cord blood immune signatures are strongly associated with offspring risk of ASD. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-021-01415-4

[ii] https://www.eurekalert.org/news-releases/939375

[iii] https://news.harvard.edu/gazette/story/2022/01/link-between-inflammation-and-autism-found-within-mouse-models/