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Link Between Autism And Gut Inflammation Uncovered In New Mouse Study

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Ben Taub

Freelance Writer

clockDec 14 2021, 12:36 UTC
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Gut inflammation

Researchers may have discovered why people with autism often suffer from gut inflammation. Image: poylock19/Shutterstock.com

People with autism spectrum disorders often display immune dysregulation, which can lead to elevated intestinal inflammation. Until now, the link between these two seemingly unconnected types of symptomologies had not been understood, yet new research on mice suggests that both may arise from exposure to inflammation while in the womb.

Appearing in the journal Immunity, the new study reveals that an inflammatory cytokine called interleukin-17a (IL-17a) appears to play a major role in both autism and gut inflammation, yet via completely separate pathways. According to the authors, prenatal exposure to this molecule may therefore represent a common underlying cause for these two co-morbid (occurring at the same time) conditions.

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The researchers began by injecting pregnant mice with a substance that mimics viral infection, triggering maternal immune activation (MIA). Pups born to these mothers displayed both autism-like traits and immune dysfunction, which caused them to develop high levels of intestinal inflammation when exposed to inflammatory stimuli later in life.

Previous research has already indicated that maternal inflammation triggers the release of IL-17a, which can interfere with fetal brain development and cause autism. To understand whether pre-natal contact with this protein also leads to immune dysregulation, the study authors allowed the pups of MIA mothers to be raised by non-MIA females, and vice versa.

Interestingly, while pups exposed to inflammation in the womb but raised by non-MIA mice continued to exhibit autism, they did not suffer from intestinal inflammation later in life. Meanwhile, those whose mothers had not been infected but were raised by MIA mice did experience gut inflammation, despite not having autism.

This finding suggests that while neurodevelopment seems to be altered prior to birth, immune function is influenced by post-natal factors. After noting major differences in the fecal microbial communities of MIA and non-MIA mothers, the team began to suspect that the maternal microbiome may affect the immune activity of offspring.

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They therefore transplanted stool from MIA mothers into mice that had been bred to lack any germs of their own, and found that pups raised by these rodents suffered from gut inflammation. In contrast, those raised by germ-free mice that had received fecal transplants from non-MIA mothers did not display such symptoms.

Taken together, these findings imply that viral infection during pregnancy may alter a mother’s microbiome, and that postnatal exposure to this maternal gut bacteria could influence immune function in offspring.

An epigenetic analysis of mouse pups that were exposed to MIA maternal microbiomes revealed that their white blood cells were slightly altered in such a way that caused them to produce excess levels of IL-17a upon contact with pathogens. In other words, the immune system of these mice became primed to trigger gut inflammation later in life.

However, when the researchers blocked IL-17a in pregnant mice using antibodies, no such inflammatory problems were seen in their offspring.

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Commenting on these findings, study author Jun R. Huh explained that there has been no mechanistic understanding of why patients with a neurodevelopmental disorder have a dysregulated immune system.”

“We’ve tied these fragmented links together. It may be that the reason is that they were exposed to this increase in inflammation during pregnancy.”

It’s important to note that this study was conducted on mice and that it is not known if the findings will hold true for humans. Nonetheless, the authors conclude that “blocking IL-17A activity in pregnant women, who are vulnerable to inflammatory conditions during pregnancy, may be used as therapeutic means to prevent the development of both neurodevelopmental and immunological disorders in offspring.”


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